HEPARIN INDUCED THROMBOCYTOPENIA AND CARDIOPULMONARY BYPASS
1: Anesth Analg 2003 Feb;96(2):344-50, table of contents
Patients with a history of type II heparin-induced thrombocytopenia with
thrombosis requiring cardiac surgery with cardiopulmonary bypass: a prospective
observational case series.
Nuttall GA, Oliver WC Jr, Santrach PJ, McBane RD, Erpelding DB, Marver CL, Zehr
KJ.
Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota 55905, USA.
nuttall,gregory@mayo.edu
Heparin-induced thrombocytopenia with thrombosis (HITT) type II is a
life-threatening complication of heparin therapy that most often occurs after
5-10 days of exposure to heparin. Anticoagulation is a significant concern for
patients with HITT type II being prepared for cardiac surgery requiring
cardiopulmonary bypass (CPB). We report a case series of 12 patients with a
history HITT type II who underwent CPB and cardiac surgery. Six patients did not
express the antibody that mediates HITT type II immediately before surgery.
Heparin was used as the anticoagulant for the duration of CPB only, and all
these patients did well without thrombotic complications. Six patients expressed
the antibody that mediates HITT type II immediately before surgery. Hirudin was
used as the anticoagulant for CPB in these patients. The ecarin clotting time
was used to guide hirudin therapy during CPB. The patients receiving hirudin did
well, but they had a large amount of bleeding, required transfusions of multiple
allogeneic blood products, and had a frequent rate of reexploration of the
mediastinum after CPB.
Publication Types:
Clinical Trial
PMID: 12538175 [PubMed - indexed for MEDLINE]
2: Heart Surg Forum 2002;5(4):354-7
Cardiac surgery in patients with heparin-induced thrombocytopenia using
preoperatively determined dosages of iloprost.
Antoniou T, Kapetanakis EI, Theodoraki K, Rellia P, Thanopoulos A, Kotiou M,
Zarkalis D, Alivizatos P.
Department of Cardiac Anesthesiology, Onassis Cardiac Surgery Center, 356 Sygrou
Avenue, Kallithea, Athens, GR-176 74, Greece. ktheodoraki@hotmail.com
BACKGROUND: Patients with preoperatively diagnosed type II heparin-induced
thrombocytopenia (HIT) scheduled for cardiopulmonary bypass (CPB) present a
challenge in their intraoperative anticoagulation management because re-exposure
to heparin may result in profound thrombocytopenia, intravascular thromboses,
bleeding, and even death. Iloprost, a prostacyclin analogue that reversibly
inhibits platelet aggregation, has been suggested as a management approach in
such cases. The purpose of this study was to assess and confirm the efficacy of
a perioperative intravenous iloprost infusion in preventing thromboembolic
complications in patients with type II HIT undergoing cardiac surgery and
requiring the use of heparin and CPB. METHODS: During a one-and-a-half-year
period, 22 patients with type II HIT presented at the Cardiac Surgery Service of
the Onassis Cardiac Center in Athens. In these patients, platelet aggregation
test results were found strongly positive at heparin serum concentrations
corresponding to those achieved during CPB. Iloprost was used in a
preoperatively, in vitro-determined, patient-specific concentration that was
assessed and modified perioperatively depending on its in vivo effect on
platelet aggregation as opposed to the conventional constant rate. RESULTS: In
the 22 patients, the preoperatively determined concentration of iloprost seemed
to correlate well with the in vivo interruption of platelet aggregation, as
tested by a perioperative heparin-induced platelet aggregation (HIPA) assay, and
in only 3 cases (14%) was the rate of iloprost infusion increased. The patients'
platelet counts, which were evaluated peri- and postoperatively, were preserved
with no statistically significant fluctuations. Postoperative bleeding was
within normal limits and no thrombotic episodes or other complications were
reported. CONCLUSION: Although a number of alternative anticoagulation methods,
such as the use of another anticoagulant (danaparoid sodium and recombinant
hirudin) or the preoperative use of a defibrinogenating agent (ancorod), have
been suggested for patients with type II HIT requiring anticoagulation during
CPB, the use of heparin associated with a potent platelet inhibitor such as the
prostacyclin analog iloprost is, as this study confirmed, the only to-date safe
and effective choice.
PMID: 12538117 [PubMed - indexed for MEDLINE]
3: Ann Thorac Surg 2003 Jan;75(1):264-5
Favorable outcome with bivalirudin anticoagulation during cardiopulmonary
bypass.
Davis Z, Anderson R, Short D, Garber D, Valgiusti A.
Edward Hospital, Naperville, Illinois, USA. zdavis@openheart.net
An 81-year-old man with previous syncopal episodes, progressive shortness of
breath, pulmonary edema, severe calcific aortic stenosis, and a history of
heparin-induced thrombocytopenia required aortic valve replacement. Bivalirudin,
a thrombin-specific anticoagulant, was used in place of heparin. The patient
received a 50 mg bivalirudin bolus followed by an infusion between 1.5 mg x
kg(-1) x h(-1) and 1.75 mg x kg(-1) x h(-1). Adequate anticoagulation was
readily obtained resulting in an uneventful cardiopulmonary bypass. Activated
clotting time (ACT) values steadily declined after discontinuation of the
bivalirudin infusion. Bivalirudin is a practical alternative to heparin during
cardiac surgical procedures.
PMID: 12537226 [PubMed - indexed for MEDLINE]
4: Br J Haematol 2002 Dec;119(3):880
Management dilemma of cardiopulmonary bypass in patients with type II
heparin-induced thrombocytopenia.
Saad RA, Horn L, Mankad PS.
PMID: 12437678 [PubMed - indexed for MEDLINE]
5: J Clin Anesth 2002 Sep;14(6):456-8
Monitoring of hirudin therapy with the Thrombelastograph.
Pivalizza EG.
Department of Anesthesiology, University of Texas Health Science Center at
Houston, MSB 5.020, 6431 Fannin Street, Houston, TX 77030, USA.
Evan.G.Pivalizza@uth.tmc.edu
Lepirudin is a specific thrombin inhibitor that is used for anticoagulation in
patients with heparin-induced thrombocytopenia who are also undergoing
cardiopulmonary bypass (CPB). Monitoring of lepirudin during CPB has been
carried out with activated clotting time and ecarin clotting time. Correlation
is poor with the former method, whereas ecarin clotting time is not widely
available. A patient is described with heparin-induced thrombocytopenia who
underwent CPB, where coagulation monitoring was accomplished with the
Thrombelastograph. This more widely available method may be useful in such
patients.
PMID: 12393117 [PubMed - indexed for MEDLINE]
6: J Clin Anesth 2002 Sep;14(6):452-5
Anticoagulation for patients with heparin-induced thrombocytopenia using
recombinant hirudin during cardiopulmonary bypass.
Liu H, Fleming NW, Moore PG.
Department of Anesthesiology and Pain Medicine, University of California-Davis
Medical Center, Sacramento, CA 95817, USA. hualiu@ucdavis.edu
Heparin-induced thrombocytopenia (HIT) is a common complication of heparin
therapy. There are three types of HIT. In the majority of patients,
thrombocytopenia is modest and resolves without sequelae (HIT I). In a smaller
number of patients, the thrombocytopenia is severe (HIT II), and in still
others, the thrombocytopenia is also associated with thrombosis (HITT).
Administration of heparin to this latter group of patients causes platelet
aggregation, thromboembolism, and thrombocytopenia. It is advisable that heparin
not be administered in any form to patients with documented or suspected HIT II
or HITT. This situation, of course, poses a problem for those patients requiring
cardiopulmonary bypass (CPB) surgery. In this report, we summarize our
experience with Lepirudin (Hoechst, Frankfurt Ammain, Germany), which is a
recombinant hirudin (r-hirudin), as an alternative to heparin for systemic
anticoagulation, as well as the use of the ecarine clotting time (ECT) for
monitoring anticoagulation status during CPB.
PMID: 12393116 [PubMed - indexed for MEDLINE]
7: Curr Opin Pulm Med 2002 Sep;8(5):405-12
Current agents for the treatment of patients with heparin-induced
thrombocytopenia.
Warkentin TE.
Department of Pathology and Molecular Medicine, McMaster University, Hamilton,
Ontario, Canada. twarkin@mcmaster.ca
Several counterintuitive treatment paradoxes complicate the management of immune
heparin-induced thrombocytopenia (HIT). For example, simple discontinuation of
heparin often fails to prevent subsequent HIT-associated thrombosis. Thus,
current treatment guidelines recommend substituting heparin with a rapidly
acting alternative anticoagulant (eg, danaparoid, lepirudin, or argatroban) even
when HIT is suspected on the basis of thrombocytopenia alone ("isolated HIT").
Another paradox-coumarin (warfarin) anticoagulation-can lead to venous limb
gangrene in a patient with HIT-associated deep-vein thrombosis. Thus, warfarin
is not recommended during acute thrombocytopenia secondary to HIT. However,
warfarin can be given as overlapping therapy with an alternative anticoagulant,
provided that (1) initiation of warfarin is delayed until substantial platelet
count recovery has occurred (to at least above 100 x 10(9)/L); (2) low initial
doses of warfarin are used; (3) at least 5 days of overlapping therapy are
given; and (4) the alternative agent is maintained until the platelet count has
normalized. It has recently been recognized that HIT antibodies are transient
and usually do not recur upon subsequent re-exposure to heparin. This leads to a
further paradox-patients with previous HIT can be considered for a brief
re-exposure to heparin under exceptional circumstances; for example, heart
surgery requiring cardiopulmonary bypass, if HIT antibodies are no longer
detectable using sensitive assays. For patients with acute or recent HIT who
require urgent heart surgery, other approaches include use of alternative
anticoagulants (eg, lepirudin or danaparoid) for cardiopulmonary bypass or
antiplatelet agents (eg, tirofiban or epoprostenol) to permit intraoperative use
of heparin.
Publication Types:
Review
Review, Tutorial
PMID: 12172444 [PubMed - indexed for MEDLINE]
8: J Card Surg 2001;16(4):313-8
Use of plasma exchange and heparin during cardiopulmonary bypass for a patient
with heparin induced thrombocytopenia: a case report.
Kajitani M, Aguinaga M, Johnson CE, Scott MA, Antakli T.
Division of Cardiothoracic Surgery, University of Arkansas for Medical Sciences,
Little Rock 72205-7199, USA.
Patients with documented history of heparin-induced thrombocytopenia (HIT) pose
a difficult problem during surgery using cardiopulmonary bypass (CPB). Several
alternatives to heparin exist, but these products either are not approved for
use in the United States or have more side effects than heparin. We report on a
patient with documented heparin-induced antibody and left main coronary artery
disease who underwent uneventful coronary artery bypass surgery and recovery by
using preoperative plasmaphresis and limited use of porcine intestinal heparin
during CPB.
PMID: 11833705 [PubMed - indexed for MEDLINE]
9: Ann Fr Anesth Reanim 2001 Nov;20(9):799-802
[Extracorporeal circulation with danaparoid sodium for valve replacement in
thrombocytopenia induced by type II heparin]
[Article in French]
Salmi L, Leroy-Matheron C, LeBesnerais P, Rosanval O, Duvaldestin P,
Gouault-Heilmann M.
Service d'anesthesie-reanimation, CHU Henri-Mondor, 94010 Creteil, France.
zergbh@noos.fr
A type II heparin-induced thrombocytopenia (HIT) was diagnosed in a 64-year-old
woman at day 20 of intravenous unfractionated heparin (UFH) therapy, given after
myocardial infarction treated by angioplasty and intracoronary stent. The
infarction was complicated by a mitral insufficiency that led to a mitral valve
replacement. Cardiopulmonary bypass was successfully performed with sodium
danaparoid (Orgaran), as an alternative to UFH, without thrombotic or
haemorrhagic complications and the follow-up was uneventful.
PMID: 11759322 [PubMed - indexed for MEDLINE]
10: J Thorac Cardiovasc Surg 2001 Dec;122(6):1254-5
One-year experience with the platelet glycoprotein IIb/IIIa antagonist tirofiban
and heparin during cardiopulmonary bypass in patients with heparin-induced
thrombocytopenia type II.
Koster A, Meyer O, Fischer T, Kukucka M, Krabatsch T, Bauer M, Kuppe H, Hetzer
R.
Department of Anaesthesiology, Deutsches Herzzentrum Berlin, Berlin, Germany.
koster@dhzb.de
PMID: 11726910 [PubMed - indexed for MEDLINE]
11: Ann Thorac Surg 2001 Nov;72(5):1730-2
Off-pump coronary artery bypass grafting for acute heparin-induced
thrombocytopenia.
Warkentin TE, Dunn GL, Cybulsky IJ.
Department of Pathology and Molecular Medicine, McMaster University, Hamilton,
Ontario, Canada.
Surgical revascularization of coronary arteries is problematic for patients with
heparin-induced thrombocytopenia because the available nonheparin anticoagulants
cannot be reversed pharmacologically. We used three-vessel off-pump coronary
artery bypass grafting in a patient with heparin-induced thrombocytopenia, as it
allowed us to use substantially lower doses of nonheparin anticoagulant
(danaparoid sodium), compared with procedures requiring cardiopulmonary bypass.
PMID: 11722075 [PubMed - indexed for MEDLINE]
12: J Extra Corpor Technol 2001 Sep;33(3):193-6
Some new perspectives in heparin-induced thrombocytopenia type II.
Koster A, Meyer O, Hetzer R, Kuppe H.
Department of Anesthesia, Deutsches Herzzentrum Berlin, Germany. Koster@DHZB.de
We conclude that HIT II is a serious complication, particularly in patients
undergoing cardiovascular surgery that involves CPB. New tests might contribute
to the earlier diagnosis of this disease. However, the reduction of immunization
by the use of alternative anticoagulants whenever possible seems to be the most
effective strategy for the reduction of HIT II-associated complications. If HIT
II is diagnosed. r-hirudin is effective as an acute therapy (especially in
combination with GP IIb/IIIa inhibitors) and also for further anticoagulation.
If patients must undergo CPB, all current alternative anticoagulation concepts
are associated with relevant drawbacks that put the patient at an increased risk
for post-operative bleeding and/or CPB thrombosis. Currently, r-hirudin is most
probably the best option for this purpose. However, when there is impaired renal
function, the persistent anticoagulant effect is associated with hemorrhage.
Further studies must evaluate whether extracorporeal elimination procedures,
such as hemofiltration or plasmapheresis, are effective in avoiding such
complications. Otherwise, the combination of UFH with a potent antiplatelet
agent, especially with short-acting GP IIb/IIIa antagonists, is an attractive
alternative.
Publication Types:
Review
Review, Tutorial
PMID: 11680734 [PubMed - indexed for MEDLINE]
13: Perfusion 2001 Sep;16(5):411-6
Alternatives to unfractionated heparin for anticoagulation in cardiopulmonary
bypass.
von Segesser LK, Mueller X, Marty B, Horisberger J, Corno A.
Department of Cardiovascular Surgery, CHUV, Centre Hospitalier Universitaire
Vaudois, Lausanne, Switzerland. Ludwig.von_Segesser@chuv.hospvd.ch
Despite the progress made in the development of cardiopulmonary bypass (CPB)
equipment, systemic anticoagulation with unfractionated heparin and post-bypass
neutralization with protamine are still used in most perfusion procedures.
However, there are a number of situations where unfractionated heparin,
protamine or both cannot be used for various reasons. Intolerance of protamine
can be addressed with extracorporeal heparin removal devices, perfusion with
(no) low systemic heparinization and, to some degree, by perfusion with
alternative anticoagulants. Various alternative anticoagulation regimens have
been used in cases of intolerance to unfractionated heparin, including extreme
hemodilution, low molecular weight heparins, danaparoid, ancrod, r-hirudin,
abciximab, tirofiban, argatroban and others. In the presence of heparin-induced
thrombocytopenia (HIT) and thrombosis, the use of r-hirudin appears to be an
acceptable solution which has been well studied. The main issue with r-hirudin
is the difficulty in monitoring its activity during CPB, despite the fact that
ecarin coagulation time assessment is now available. A more recent approach is
based on selective blockage of platelet aggregation by means of monoclonal
antibodies directed to GPIIb/IIIa receptors (abciximab) or the use of a
GPIIb/IIIa inhibitor (tirofiban). An 80% blockage of the GPIIb/IIIa receptors
and suppression of platelet aggregation to less than 20% allows the giving of
unfractionated heparin and running CPB in a standard fashion despite HIT and
thrombosis. Likewise, at the end of the procedure, unfractionated heparin is
neutralized with protamine as usual and donor platelets are transfused if
necessary. GPIIb/IIIa inhibitors are frequently used in interventional
cardiology and, therefore, are available in most hospitals.
Publication Types:
Review
Review, Tutorial
PMID: 11565896 [PubMed - indexed for MEDLINE]
14: J Extra Corpor Technol 2001 May;33(2):117-25
Use of ecarin clotting time (ECT) with lepirudin therapy in heparin-induced
thrombocytopenia and cardiopulmonary bypass.
Fabrizio MC.
UPMC Presbyterian Perfusion Services Department, University of Pittsburgh
Medical Center, Pennsylvania 15213, USA. fabriziomc@msx.upmc.edu
Heparin-induced thrombocytopenia (HIT) is described as an allergy-like adverse
reaction to heparin. It is a potentially severe complication of heparin therapy
that can result in serious or life-threatening venous or arterial thromboembolic
events. In the United States, lepirudin (Aventis Pharma AG, Strasbourg, France)
is an approved therapy for anticoagulation in patients with HIT requiring
anticoagulation. Lepirudin is a recombinant form of hirudin, a leech enzyme that
is a highly specific direct inhibitor of thrombin. Lepirudin monitoring during
surgery can be managed with ecarin clotting time (ECT) (Cardiovascular
Diagnostics, Inc., Raleigh, NC), which has recently been approved as a
humanitarian device exemption (HDE) for use in the United States in the
management of HIT with cardiopulmonary bypass. This case report describes a
patient with HIT who was managed successfully with lepirudin and ECT during
coronary artery bypass grafting.
PMID: 11467439 [PubMed - indexed for MEDLINE]
15: Anesth Analg 2001 Jul;93(1):28-32
The relationship between hirudin and activated clotting time: implications for
patients with heparin-induced thrombocytopenia undergoing cardiac surgery.
Despotis GJ, Hogue CW, Saleem R, Bigham M, Skubas N, Apostolidou I, Qayum A,
Joist JH.
Departments of Anesthesiology, Pathology and ImmunologyWashington University
School of Medicine, St. Louis, Missouri 63110, USA.
Anticoagulation with recombinant hirudin (r-hirudin) (Refludan) has been
suggested as an alternative to heparin for patients with heparin-induced
thrombocytopenia requiring cardiac surgery. We sought to develop a modified
activated coagulation time (ACT) that would allow quantification of the levels
of r-hirudin required during cardiopulmonary bypass (CPB). Twenty-one patients
scheduled for elective cardiac surgical procedures requiring CPB were enrolled
in this IRB-approved study. R-hirudin was added to blood specimens obtained
before heparin administration (before CPB) and 30 min after heparin
neutralization with protamine (after CPB) to result in concentrations of 0, 2,
4, 6, 7, or 8 microg/mL. Kaolin/ACT and complete blood count measurements were
assayed in native specimens (first 10 patients, Phase I) or in specimens mixed
with equal volumes of commercial normal plasma (second 11 patients, Phase II).
In Phase I, good (r(2) = 0.83) linear relationships between ACT values and
r-hirudin concentrations (< or =4 microg/mL) were observed in specimens obtained
before CPB. However, ACT values were markedly prolonged (P < 0.0001) by
r-hirudin in specimens obtained after CPB, with ACT values generally exceeding
the ACT's detection limit (>999 s) at hirudin concentrations >2 microg/mL. In
patient specimens mixed with normal plasma (Phase II), ACT/hirudin relationships
(i.e., hirudin/ACT slope values obtained with hirudin concentration < or =4
microg/mL) in the post-CPB period (0.022 +/- 0.004 microg. mL(-1). s(-1)) were
similar (P = 0.47) to those (0.019 +/- 0.004 microg. mL(-1). s(-1)) obtained in
the pre-CPB period. Accordingly, a significant relationship between normal
plasma-supplemented ACT values and predilution hirudin concentration was
obtained in the post-CPB (hirudin = 0.039ACT - 4.34, r(2) = 0.91) period.
Although our data demonstrate that the ACT test cannot be used to monitor
hirudin during CPB, the addition of 50% normal plasma to post-CPB hemodiluted
blood specimens yields a consistent linear relationship between hirudin
concentration and ACT values up to a predilution concentration of 8 microg/mL.
Plasma-modified ACT may be useful in monitoring hirudin anticoagulation during
CPB. Implications: A modified activated clotting time test system that may be
helpful in monitoring hirudin anticoagulation in patients with heparin-induced
thrombocytopenia during cardiac surgery with cardiopulmonary bypass is
described.
Publication Types:
Clinical Trial
PMID: 11429333 [PubMed - indexed for MEDLINE]
16: Ann Thorac Surg 2001 Jun;71(6):1920-4
Heparin-induced thrombocytopenia: bovine versus porcine heparin in
cardiopulmonary bypass surgery.
Konkle BA, Bauer TL, Arepally G, Cines DB, Poncz M, McNulty S, Edie RN, Mannion
JD.
Department of Medicine, Cardeza Foundation for Hematologic Research, Jefferson
Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
konkleb@mail.med.upenn.edu
BACKGROUND: Studies have demonstrated a high incidence of antibodies to
heparin/platelet factor 4 complexes, the antigen in heparin-induced
thrombocytopenia, in patients after cardiopulmonary bypass surgery. In many
hospitals, beef lung heparin has been used historically for cardiopulmonary
bypass, and there has been reluctance to change to porcine heparin despite
concerns of an increased incidence of heparin-induced thrombocytopenia in
patients receiving bovine heparin. METHODS: A prospective randomized trial
comparing bovine and porcine heparin in cardiopulmonary bypass surgery was
conducted. Presurgery and postsurgery heparin antibody formation was studied
using the serotonin release assay and a heparin/platelet factor 4 enzyme-linked
immunosorbent assay. RESULTS: Data available on 98 patients, randomized to
receive either bovine or porcine heparin, revealed no significant difference in
patient positivity by serotonin release assay (12% in both groups) or by the
heparin/platelet factor 4 enzyme-linked immunosorbent assay (29% with porcine
and 35% with bovine heparin) postoperatively. There were no significant
differences between preoperative and postoperative platelet counts or
thromboembolic complications. CONCLUSIONS: Our study does not support the belief
that bovine heparin is more likely than porcine heparin to induce the
development of antibodies to heparin/platelet factor 4.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 11426769 [PubMed - indexed for MEDLINE]
17: Eur J Cardiothorac Surg 2001 Apr;19(4):525-7
Budd--Chiari syndrome and heparin-induced thrombocytopenia.
Carrel T, Berdat P, Schmidli J, Gygax E.
Clinic for Cardiovascular Surgery, University Hospital, CH-3010 Berne,
Switzerland. thierry.carrel@insel.ch
We report on a patient suffering from Budd--Chiari disease who developed
heparin-induced thrombocytopenia preoperatively. Dorsocranial liver resection
and hepatoatrial anastomosis were performed with the extracorporeal circulation
and perioperative anticoagulation was achieved with r-hirudin. Surprisingly,
thrombus formation was observed in the venous reservoir although ACT was 590 s
and aPTT 55 s. An additional bolus of hirudin and rinsing the reservoir allowed
unproblematic discontinuation of the cardiopulmonary bypass.
PMID: 11306328 [PubMed - indexed for MEDLINE]
18: Ann Thorac Surg 2001 Mar;71(3):1041-2
Emergency cardiopulmonary bypass in a bilaterally nephrectomized patient with a
history of heparin-induced thrombocytopenia: successful reexposure to heparin.
Selleng S, Lubenow N, Wollert HG, Mullejans B, Greinacher A.
Department of Anesthesiology and Critical Care, Heart and Diabetes Centre
Mecklenburg-Vorpommern, Karlsburg, Germany.
We present a case of emergency coronary artery bypass surgery in a bilaterally
nephrectomized patient with a history of heparin-induced thrombocytopenia. The
patient was reexposed short term to heparin during cardiopulmonary bypass and
did not develop any complications related to heparin-induced thrombocytopenia.
Despite intraoperative neutralization of heparin severe bleeding complications
occurred, probably resulting from preoperative therapeutic anticoagulation with
rhirudin in conjunction with an increased half-life of more than 2 days.
PMID: 11269430 [PubMed - indexed for MEDLINE]
19: Arch Mal Coeur Vaiss 2001 Feb;94(2):144-7
[Use of Organon, a synthetic heparinoid, in two cardiopulmonary bypass
procedures in the same patient sensitive to heparin]
[Article in French]
Pineau E, Le Bret E, Folliguet T, Saint Maurice OS, Carbognani D, Laborde F.
Departement cardiovasculaire, Institut mutualiste Montsouris, 42, boulevard
Jourdan, 75674 Paris.
We report the case of a patient who underwent two cardiopulmonary bypass (CPB)
procedures with Orgaran because of heparin-induced thrombocytopenia. A 38
years-old man with ischemic mitral insufficiency was operated for coronary
artery bypass and valvular replacement. The CPB was carried out with heparin.
Heparin-induced thrombocytopenia occured and was proven immunologically. Two
months later, a new valvular replacement was performed because of paravalvular
leak due to endocarditis. The Orgaran-CPB protocol was as follows: 5,000 units
before cardiopulmonary bypass, 5,000 units in the priming volume, anti-Xa level
between 0.9 and 1.1 units/mL, with injection of 1,500 units if necessary, no
administration of protamine. One month later, a new valvular replacement was
necessary and performed with the same protocol using Orgaran. No bleeding or
thrombotic complication occurred. Orgaran is a safe and reliable anti-thrombotic
substitute if anti-Xa activity is closely monitored.
Publication Types:
Review
Review of Reported Cases
PMID: 11265553 [PubMed - indexed for MEDLINE]
20: Ann Thorac Surg 2001 Feb;71(2):678-83
Cardiac surgery with cardiopulmonary bypass in patients with type II
heparin-induced thrombocytopenia.
Aouifi A, Blanc P, Piriou V, Bastien OH, Ffrench P, Hanss M, Lehot JJ.
Service d'Anesthesie--Reanimation and EA 1896, Universite Claude Bernard Lyon I,
France. a.aouifi@free.fr
BACKGROUND: The use of cardiopulmonary bypass (CPB) in patients with a history
of type II heparin-induced thrombocytopenia (HIT) may be associated with
complications related to their anticoagulation management. METHODS: Between
January 1997 and December 1999, among 4,850 adults patients who underwent
cardiac surgery in our institution, 10 patients presented with preoperative type
II HIT. In 4 patients, anticoagulation during CPB was achieved with danaparoid
sodium. In 6 other patients, heparin sodium was used after pretreatment with
epoprostenol sodium. RESULTS: No significant change in platelet count occurred
in any patient. No intraoperative thrombotic complication was encountered. Total
postoperative chest drainage ranged from 250 to 1,100 ml in patients pretreated
with epoprostenol and 1,700 to 2,470 ml in patients who received danaparoid
sodium during CPB (p < 0.05, Mann-Whitney U test). CONCLUSIONS: During CPB,
inhibition of platelet aggregation by prostacyclin may be a safe anticoagulation
approach in patients with type II HIT.
PMID: 11235727 [PubMed - indexed for MEDLINE]
21: N Engl J Med 2000 Dec 28;343(26):1973
Comment on:
N Engl J Med. 2000 Aug 17;343(7):515.
Heparin-induced thrombocytopenia and cardiopulmonary bypass.
Nash I.
Publication Types:
Comment
Letter
PMID: 11186681 [PubMed - indexed for MEDLINE]
22: Anesthesiology 2001 Feb;94(2):245-51
Anticoagulation during cardiopulmonary bypass in patients with heparin-induced
thrombocytopenia type II and renal impairment using heparin and the platelet
glycoprotein IIb-IIIa antagonist tirofiban.
Koster A, Kukucka M, Bach F, Meyer O, Fischer T, Mertzlufft F, Loebe M, Hetzer
R, Kuppe H.
Department of Anesthesia, Deutsches Herzzentrum Berlin, Berlin Germany.
koster@dhzb.de
BACKGROUND: Patients with heparin-induced thrombocytopenia type II require an
alternative to standard heparin anticoagulation. However, in patients with renal
impairment, anticoagulation during cardiopulmonary bypass with agents such as
danaparoid sodium or r-hirudin are associated with hemorrhage. Anticoagulation
with unfractionated heparins combined with prostacyclin, a potent platelet
aggregation inhibitor, is associated with severe hypotension. The authors
investigated a new concept using unfractionated heparins after platelet
inhibition with the short-acting platelet glycoprotein IIb-IIIa antagonist
tirofiban. METHODS: Ten patients with heparin-induced thrombocytopenia type II
and renal impairment were enrolled in the investigation. All had heparin-induced
thrombocytopenia type II antibodies present as proved by the heparin-induced
platelet aggregation assay, the heparin-platelet factor 4 enzyme-linked
immunosorbent assay, or both. In all patients, preoperative anticoagulation to
an activated partial thromboplastin time of 40-60 s was performed with
r-hirudin. Anticoagulation during cardiopulmonary bypass was achieved with a
bolus of 400 IU/kg unfractionated heparins after a bolus of tirofiban 10
microg/kg followed by an infusion of tirofiban at a rate of 0.15 microg x kg(-1)
x min(-1) until 1 h before conclusion of cardiopulmonary bypass. Additional
unfractionated heparins were only administered if activated clotting time
decreased below 480 s. Coagulation was monitored by a abciximab-modified TEG and
the adenosine diphosphate-stimulated (20 microm) platelet aggregometry. D-dimer
concentrations, as a marker of venous thromboembolism, were measured before and
12, 24, and 48 h after surgery. Postoperative antithrombotic therapy was started
immediately with r-hirudin to anticoagulation to an activated partial
thromboplastin time of 40-60 s. RESULTS: The postoperative blood loss ranged
from 110 to 520 ml. No patient needed reexploration. In no patient was there
clinical evidence of thrombosis or embolism in the postoperative period or of a
critical increase of the D-dimer concentrations, suggesting venous
thromboembolism. Transfusion of platelets was necessary in only two patients.
CONCLUSIONS: The protocol is easy to perform and no increased postoperative
bleeding and no thromboembolic complications occurred. The combination of
unfractionated heparins and tirofiban may be an alternative to other
anticoagulation strategies in patients with heparin-induced thrombocytopenia.
PMID: 11176088 [PubMed - indexed for MEDLINE]
23: Ann Thorac Surg 2000 Dec;70(6):2173-81
Cardiopulmonary bypass in patients with heparin-induced thrombocytopenia and
thrombosis.
Follis F, Schmidt CA.
Department of Cardiothoracic Surgery, University of New Mexico Health Sciences
Center, Albuquerque, USA. follis99@hotmail.com
Heparin-induced thrombocytopenia and thrombosis (HITT) is an immunomediated
disorder induced by the administration of heparin for therapeutic purposes. The
presence of this condition in patients requiring full heparinization for
cardiopulmonary bypass constitutes a formidable challenge for the cardiac
surgeon. In this review, the clinical and experimental experience described in
the literature are discussed in the perspective of the normal coagulation and
the pathophysiology of HITT and in the light of a variety of old and new
alternative anticoagulants.
Publication Types:
Review
Review of Reported Cases
PMID: 11156153 [PubMed - indexed for MEDLINE]
24: Ann Thorac Surg 2000 Dec;70(6):2160-1
Cardiopulmonary bypass in a patient with heparin-induced thrombocytopenia II and
impaired renal function using heparin and the platelet GP IIb/IIIa inhibitor
tirofiban as anticoagulant.
Koster A, Loebe M, Mertzlufft F, Kuppe H, Hetzer R.
Department of Anesthesia, Deutsches Herzzentrum Berlin. koster@dhzb.de
In a patient with heparin-induced thrombocytopenia II and impaired renal
function, anticoagulation during cardiopulmonary bypass was successfully
performed by the use of unfractionated heparin and the platelet glycoprotein
IIb/IIIa inhibitor tirofiban. Postoperative antithrombotic therapy with
recombinant hirudin was immediately initiated. This regimen for anticoagulation
for cardiopulmonary bypass in patients with heparin-induced thrombocytopenia II
appears to be particularly appropriate for patients with impaired renal function
or for hospitals without special experience with other alternative
anticoagulation strategies.
PMID: 11156147 [PubMed - indexed for MEDLINE]
25: J Cardiothorac Vasc Anesth 2000 Dec;14(6):707-9
Use of danaparoid during cardiopulmonary bypass in patients with heparin-induced
thrombocytopenia.
Olin DA, Urdaneta F, Lobato EB.
Department of Anesthesiology, University of Florida College of Medicine, and the
Gainesville Veterans Affairs Medical Center, USA.
PMID: 11139115 [PubMed - indexed for MEDLINE]
26: Perfusion 2000 Nov;15(6):531-9
Use of danaparoid sodium (Orgaran) as an alternative to heparin sodium during
cardiopulmonary bypass: a clinical evaluation of six cases.
Fernandes P, Mayer R, MacDonald JL, Cleland AG, Hay-McKay C.
Clinical Perfusion Services, London Health Sciences Centre, Ontario, Canada.
philip.fernandes@lhsc.on.ca
Heparin-induced thrombocytopenia (HIT) has become more prevalent in today's
cardiac setting and has resulted in the need for alternative anticoagulant
therapies. Danaparoid sodium, one alternative to heparin, has been used in six
cardiopulmonary bypass procedures in this hospital. This clinical experience has
resulted in the progressive refinement of a protocol for the 'safe' clinical use
of danaparoid sodium. Although there were six positive outcomes with the use of
danaparoid sodium, alternatives must be explored in order to find the optimal
anticoagulant for the treatment of HIT.
PMID: 11131218 [PubMed - indexed for MEDLINE]
27: Ann Thorac Surg 2000 Oct;70(4):1434-43
Cardiopulmonary bypass in humans: bypassing unfractionated heparin.
Frederiksen JW.
Department of Surgery, Northwestern University Medical School, Chicago, Illinois
60611, USA. jwf@nwu.edu
Seven anticoagulants besides unfractionated heparin have been used for human
cardiopulmonary bypass (CPB), mainly in patients with heparin-induced
thrombocytopenia. The collective experience with these alternative
anticoagulants provides a perspective on current efforts aimed at improving CPB
anticoagulation. Unfortunately, each alternative currently lacks a standard
dosing schedule and a reliable method of monitoring the adequacy of its
anticoagulant effect during CPB. Most also lack proven antidotes. Thus,
unfractionated heparin remains the anticoagulant of choice for standard CPB.
Publication Types:
Review
Review, Tutorial
PMID: 11081925 [PubMed - indexed for MEDLINE]
28: Acta Anaesthesiol Scand 2000 Sep;44(8):991-3
Comment in:
Acta Anaesthesiol Scand. 2001 May;45(5):655.
Heparin-induced thrombocytopenia thrombosis after cardiac surgery. A case
report.
Antoniou T, Stavridis G, Daganou M, Melissari E, Gatzonis S.
Department ofAnesthesia and Surgery, Onassis Cardiac Surgery Center, Athens,
Greece.
We report a rare case of cerebral infarct resulting in brain death due to
heparin-induced thrombocytopenia thrombosis (HITT), manifested in the immediate
postoperative period following aortic valve replacement in a 46-year-old woman
whose only prior exposure to heparin was during catheterization four months
prior to surgery. The diagnosis of HITT was suspected after a significant
decrease of the platelet count and it was confirmed by a heparin-induced
platelet activation assay showing platelet aggregation in the presence of
heparin.
PMID: 10981578 [PubMed - indexed for MEDLINE]
29: J Heart Lung Transplant 2000 Aug;19(8):810-4
Management strategies for heparin-induced thrombocytopenia in heart-transplant
candidates: case report and review of the literature.
Pamboukian SV, Ignaszewski AP, Ross HJ.
Cardiac Transplant and Heart Failure fellow,a Rush Presbyterian St. Luke's
Medical Center, Chicago, Illinois, USA.
Management of anticoagulation in patients with heparin-induced thrombocytopenia
(HIT) undergoing surgery requiring cardiopulmonary bypass (CPB), such as cardiac
transplantation, represents a difficult clinical problem and no clear management
strategy exists. The cases of 2 patients with HIT who underwent cardiac
transplantation using differing anticoagulation strategies are presented with a
discussion of potential advantages and pitfalls of each approach used.
PMID: 10967277 [PubMed - indexed for MEDLINE]
30: Anesth Analg 2003 Feb;96(2):344-50, table of contents
Patients with a history of type II heparin-induced thrombocytopenia with
thrombosis requiring cardiac surgery with cardiopulmonary bypass: a prospective
observational case series.
Nuttall GA, Oliver WC Jr, Santrach PJ, McBane RD, Erpelding DB, Marver CL, Zehr
KJ.
Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota 55905, USA.
nuttall,gregory@mayo.edu
Heparin-induced thrombocytopenia with thrombosis (HITT) type II is a
life-threatening complication of heparin therapy that most often occurs after
5-10 days of exposure to heparin. Anticoagulation is a significant concern for
patients with HITT type II being prepared for cardiac surgery requiring
cardiopulmonary bypass (CPB). We report a case series of 12 patients with a
history HITT type II who underwent CPB and cardiac surgery. Six patients did not
express the antibody that mediates HITT type II immediately before surgery.
Heparin was used as the anticoagulant for the duration of CPB only, and all
these patients did well without thrombotic complications. Six patients expressed
the antibody that mediates HITT type II immediately before surgery. Hirudin was
used as the anticoagulant for CPB in these patients. The ecarin clotting time
was used to guide hirudin therapy during CPB. The patients receiving hirudin did
well, but they had a large amount of bleeding, required transfusions of multiple
allogeneic blood products, and had a frequent rate of reexploration of the
mediastinum after CPB.
Publication Types:
Clinical Trial
PMID: 12538175 [PubMed - indexed for MEDLINE]
31: Heart Surg Forum 2002;5(4):354-7
Cardiac surgery in patients with heparin-induced thrombocytopenia using
preoperatively determined dosages of iloprost.
Antoniou T, Kapetanakis EI, Theodoraki K, Rellia P, Thanopoulos A, Kotiou M,
Zarkalis D, Alivizatos P.
Department of Cardiac Anesthesiology, Onassis Cardiac Surgery Center, 356 Sygrou
Avenue, Kallithea, Athens, GR-176 74, Greece. ktheodoraki@hotmail.com
BACKGROUND: Patients with preoperatively diagnosed type II heparin-induced
thrombocytopenia (HIT) scheduled for cardiopulmonary bypass (CPB) present a
challenge in their intraoperative anticoagulation management because re-exposure
to heparin may result in profound thrombocytopenia, intravascular thromboses,
bleeding, and even death. Iloprost, a prostacyclin analogue that reversibly
inhibits platelet aggregation, has been suggested as a management approach in
such cases. The purpose of this study was to assess and confirm the efficacy of
a perioperative intravenous iloprost infusion in preventing thromboembolic
complications in patients with type II HIT undergoing cardiac surgery and
requiring the use of heparin and CPB. METHODS: During a one-and-a-half-year
period, 22 patients with type II HIT presented at the Cardiac Surgery Service of
the Onassis Cardiac Center in Athens. In these patients, platelet aggregation
test results were found strongly positive at heparin serum concentrations
corresponding to those achieved during CPB. Iloprost was used in a
preoperatively, in vitro-determined, patient-specific concentration that was
assessed and modified perioperatively depending on its in vivo effect on
platelet aggregation as opposed to the conventional constant rate. RESULTS: In
the 22 patients, the preoperatively determined concentration of iloprost seemed
to correlate well with the in vivo interruption of platelet aggregation, as
tested by a perioperative heparin-induced platelet aggregation (HIPA) assay, and
in only 3 cases (14%) was the rate of iloprost infusion increased. The patients'
platelet counts, which were evaluated peri- and postoperatively, were preserved
with no statistically significant fluctuations. Postoperative bleeding was
within normal limits and no thrombotic episodes or other complications were
reported. CONCLUSION: Although a number of alternative anticoagulation methods,
such as the use of another anticoagulant (danaparoid sodium and recombinant
hirudin) or the preoperative use of a defibrinogenating agent (ancorod), have
been suggested for patients with type II HIT requiring anticoagulation during
CPB, the use of heparin associated with a potent platelet inhibitor such as the
prostacyclin analog iloprost is, as this study confirmed, the only to-date safe
and effective choice.
PMID: 12538117 [PubMed - indexed for MEDLINE]
32: Ann Thorac Surg 2003 Jan;75(1):264-5
Favorable outcome with bivalirudin anticoagulation during cardiopulmonary
bypass.
Davis Z, Anderson R, Short D, Garber D, Valgiusti A.
Edward Hospital, Naperville, Illinois, USA. zdavis@openheart.net
An 81-year-old man with previous syncopal episodes, progressive shortness of
breath, pulmonary edema, severe calcific aortic stenosis, and a history of
heparin-induced thrombocytopenia required aortic valve replacement. Bivalirudin,
a thrombin-specific anticoagulant, was used in place of heparin. The patient
received a 50 mg bivalirudin bolus followed by an infusion between 1.5 mg x
kg(-1) x h(-1) and 1.75 mg x kg(-1) x h(-1). Adequate anticoagulation was
readily obtained resulting in an uneventful cardiopulmonary bypass. Activated
clotting time (ACT) values steadily declined after discontinuation of the
bivalirudin infusion. Bivalirudin is a practical alternative to heparin during
cardiac surgical procedures.
PMID: 12537226 [PubMed - indexed for MEDLINE]
33: Ann Thorac Surg 2003 Jan;75(1):17-22
Comment in:
Ann Thorac Surg. 2003 Jan;75(1):15-6.
Comparison of bovine and porcine heparin in heparin antibody formation after
cardiac surgery.
Francis JL, Palmer GJ 3rd, Moroose R, Drexler A.
Center for Hemostasis and Thrombosis, Department of Thoracic Cardiovascular
Surgery, Florida Hospital, 2501 N. Orange Ave, Suite 786, Orlando, FL 32804,
USA. john.francis@flhosp.org
BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a potentially devastating
complication of heparin therapy. The incidence of clinical HIT after
cardiovascular surgery is less than 2%, although asymptomatic antibodies to
heparin-platelet factor 4 (PF4) occur more frequently. Bovine heparin is thought
to cause more HIT than porcine heparin, although this has never been established
for heparin use during coronary artery bypass grafting. We therefore undertook a
randomized, prospective study of heparin-PF4 antibody formation in patients
undergoing first-time CABG given intraoperative bovine or porcine heparin.
METHODS: Two hundred seven patients (108 porcine, 99 bovine) completed the
study. Heparin given pre- or postoperatively was always porcine. Platelet counts
and heparin-PF4 antibody tests (enzyme-linked immunosorbent assays) were
performed preoperatively and daily until postoperative day 7 or discharge if
earlier. RESULTS: The overall incidence of heparin-PF4 antibody formation was
42%. Six patients (2.9%) were positive preoperatively, of which, 1 developed
clinical HIT. When these were excluded, seroconversion rates were 44 of 99
(44.4%) and 33 of 108 (30.6%) for bovine and porcine heparin, respectively (p =
0.041). Among patients who produced antibodies, most (90% bovine, 85% porcine)
seroconverted after postoperative day 2. There were no differences in
postoperative platelet counts; only 1 patient developed thrombosis associated
with seroconversion, but without developing thrombocytopenia. The seroconversion
rates for patients having cardiopulmonary bypass or off-pump surgery were not
significantly different. CONCLUSIONS: This study confirms the high frequency of
heparin-PF4 antibodies after coronary artery bypass grafting and demonstrates a
significantly higher incidence after bovine heparin. However, because some
patients may seroconvert after discharge, our study may underestimate the true
incidence.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 12537186 [PubMed - indexed for MEDLINE]
34: Br J Haematol 2002 Dec;119(3):880
Management dilemma of cardiopulmonary bypass in patients with type II
heparin-induced thrombocytopenia.
Saad RA, Horn L, Mankad PS.
PMID: 12437678 [PubMed - indexed for MEDLINE]
35: J Clin Anesth 2002 Sep;14(6):456-8
Monitoring of hirudin therapy with the Thrombelastograph.
Pivalizza EG.
Department of Anesthesiology, University of Texas Health Science Center at
Houston, MSB 5.020, 6431 Fannin Street, Houston, TX 77030, USA.
Evan.G.Pivalizza@uth.tmc.edu
Lepirudin is a specific thrombin inhibitor that is used for anticoagulation in
patients with heparin-induced thrombocytopenia who are also undergoing
cardiopulmonary bypass (CPB). Monitoring of lepirudin during CPB has been
carried out with activated clotting time and ecarin clotting time. Correlation
is poor with the former method, whereas ecarin clotting time is not widely
available. A patient is described with heparin-induced thrombocytopenia who
underwent CPB, where coagulation monitoring was accomplished with the
Thrombelastograph. This more widely available method may be useful in such
patients.
PMID: 12393117 [PubMed - indexed for MEDLINE]
36: J Clin Anesth 2002 Sep;14(6):452-5
Anticoagulation for patients with heparin-induced thrombocytopenia using
recombinant hirudin during cardiopulmonary bypass.
Liu H, Fleming NW, Moore PG.
Department of Anesthesiology and Pain Medicine, University of California-Davis
Medical Center, Sacramento, CA 95817, USA. hualiu@ucdavis.edu
Heparin-induced thrombocytopenia (HIT) is a common complication of heparin
therapy. There are three types of HIT. In the majority of patients,
thrombocytopenia is modest and resolves without sequelae (HIT I). In a smaller
number of patients, the thrombocytopenia is severe (HIT II), and in still
others, the thrombocytopenia is also associated with thrombosis (HITT).
Administration of heparin to this latter group of patients causes platelet
aggregation, thromboembolism, and thrombocytopenia. It is advisable that heparin
not be administered in any form to patients with documented or suspected HIT II
or HITT. This situation, of course, poses a problem for those patients requiring
cardiopulmonary bypass (CPB) surgery. In this report, we summarize our
experience with Lepirudin (Hoechst, Frankfurt Ammain, Germany), which is a
recombinant hirudin (r-hirudin), as an alternative to heparin for systemic
anticoagulation, as well as the use of the ecarine clotting time (ECT) for
monitoring anticoagulation status during CPB.
PMID: 12393116 [PubMed - indexed for MEDLINE]
37: Curr Opin Pulm Med 2002 Sep;8(5):405-12
Current agents for the treatment of patients with heparin-induced
thrombocytopenia.
Warkentin TE.
Department of Pathology and Molecular Medicine, McMaster University, Hamilton,
Ontario, Canada. twarkin@mcmaster.ca
Several counterintuitive treatment paradoxes complicate the management of immune
heparin-induced thrombocytopenia (HIT). For example, simple discontinuation of
heparin often fails to prevent subsequent HIT-associated thrombosis. Thus,
current treatment guidelines recommend substituting heparin with a rapidly
acting alternative anticoagulant (eg, danaparoid, lepirudin, or argatroban) even
when HIT is suspected on the basis of thrombocytopenia alone ("isolated HIT").
Another paradox-coumarin (warfarin) anticoagulation-can lead to venous limb
gangrene in a patient with HIT-associated deep-vein thrombosis. Thus, warfarin
is not recommended during acute thrombocytopenia secondary to HIT. However,
warfarin can be given as overlapping therapy with an alternative anticoagulant,
provided that (1) initiation of warfarin is delayed until substantial platelet
count recovery has occurred (to at least above 100 x 10(9)/L); (2) low initial
doses of warfarin are used; (3) at least 5 days of overlapping therapy are
given; and (4) the alternative agent is maintained until the platelet count has
normalized. It has recently been recognized that HIT antibodies are transient
and usually do not recur upon subsequent re-exposure to heparin. This leads to a
further paradox-patients with previous HIT can be considered for a brief
re-exposure to heparin under exceptional circumstances; for example, heart
surgery requiring cardiopulmonary bypass, if HIT antibodies are no longer
detectable using sensitive assays. For patients with acute or recent HIT who
require urgent heart surgery, other approaches include use of alternative
anticoagulants (eg, lepirudin or danaparoid) for cardiopulmonary bypass or
antiplatelet agents (eg, tirofiban or epoprostenol) to permit intraoperative use
of heparin.
Publication Types:
Review
Review, Tutorial
PMID: 12172444 [PubMed - indexed for MEDLINE]
38: Ann Thorac Surg 2002 May;73(5):1626-7
Erratum in:
Ann Thorac Surg 2002 Aug;74(2):635
Lifesaving citrate anticoagulation to bridge ineffective danaparoid [correction
of to bridge to danaparoid] treatment.
Dworschak M, Hiesmayr JM, Lassnigg A.
Department of Cardiothoracic Anesthesia and Intensive Care, University Hospital
Vienna, Austria. dworschak.martin@mayo.edu
A case of successful regional anticoagulation with trisodium citrate in a
patient who developed heparin-induced thrombocytopenia while on continuous
hemofiltration is described. Immediate citrate anticoagulation allowed for
maintenance of extracorporeal circulation until effective danaparoid therapy
could be established. Recommended plasma antifactor Xa levels for hemodialysis
may be inadequate in some cases. Values similar to those in use during
cardiopulmonary bypass could be required.
PMID: 12022563 [PubMed - indexed for MEDLINE]
39: Vasa 2002 Feb;31(1):62-5
Fulminate intracardiac thrombosis associated with Budd-Chiari-syndrome and
inferior vena cava thrombosis.
Eckel F, Huber W, Heidecke CD, Moessmer G, Berger H, Holper K, Dietrich W,
Lersch C, Siewert JR.
Department of Medicine II, Klinikum rechts der Isar, Technische Universitat
Munchen, Germany. florian.eckel@lrz.tum.de
The most common cause of edema of the legs and dyspnea is congestive heart
failure. Further differential diagnosis such as renal or hepatic failure have to
be considered. We report the case of a previous healthy 65-year-old woman who
developed dyspnea and massive edema of the legs followed by acute hepatic and
renal failure. Imaging studies showed a thrombosis of the inferior vena cava
(IVC) caused by a tumor between the right kidney and the IVC. Histological
examination revealed a leiomyosarcoma of the IVC. Hepatic failure due to venous
outflow obstruction (Budd-Chiari syndrome, BCS) was diagnosed. Coagulation
profile showed a complex disorder due to acute hepatic failure. Factor V Leiden
and prothrombin gene mutation G20210A could be excluded. The thrombosis extended
from the femoral veins up to the right atrium. After 11 days of anticoagulation
with heparin platelet counts decreased by more than 50%. Suspecting a
heparin-induced thrombocytopenia the patient was placed on recombinant hirudin
(lepirudin) for anticoagulation. Hepatic venogram showed a thrombosis of the
hepatic vein orifices but not of the hepatic veins. The tumor and the thrombi
were removed surgically. When the cardiopulmonary bypass was terminated new
intracardiac thrombi occurred. Despite immediate surgical intervention the
patient finally died due to right ventricular failure caused by the fulminate
intracardiac thrombosis. In conclusion, thrombosis of the IVC may mimic
congestive heart failure and may cause BCS. Neoplasms and coagulation disorders
may cause thrombosis of the IVC.
PMID: 11951701 [PubMed - indexed for MEDLINE]
40: J Card Surg 2001;16(4):313-8
Use of plasma exchange and heparin during cardiopulmonary bypass for a patient
with heparin induced thrombocytopenia: a case report.
Kajitani M, Aguinaga M, Johnson CE, Scott MA, Antakli T.
Division of Cardiothoracic Surgery, University of Arkansas for Medical Sciences,
Little Rock 72205-7199, USA.
Patients with documented history of heparin-induced thrombocytopenia (HIT) pose
a difficult problem during surgery using cardiopulmonary bypass (CPB). Several
alternatives to heparin exist, but these products either are not approved for
use in the United States or have more side effects than heparin. We report on a
patient with documented heparin-induced antibody and left main coronary artery
disease who underwent uneventful coronary artery bypass surgery and recovery by
using preoperative plasmaphresis and limited use of porcine intestinal heparin
during CPB.
PMID: 11833705 [PubMed - indexed for MEDLINE]
41: Ann Fr Anesth Reanim 2001 Nov;20(9):799-802
[Extracorporeal circulation with danaparoid sodium for valve replacement in
thrombocytopenia induced by type II heparin]
[Article in French]
Salmi L, Leroy-Matheron C, LeBesnerais P, Rosanval O, Duvaldestin P,
Gouault-Heilmann M.
Service d'anesthesie-reanimation, CHU Henri-Mondor, 94010 Creteil, France.
zergbh@noos.fr
A type II heparin-induced thrombocytopenia (HIT) was diagnosed in a 64-year-old
woman at day 20 of intravenous unfractionated heparin (UFH) therapy, given after
myocardial infarction treated by angioplasty and intracoronary stent. The
infarction was complicated by a mitral insufficiency that led to a mitral valve
replacement. Cardiopulmonary bypass was successfully performed with sodium
danaparoid (Orgaran), as an alternative to UFH, without thrombotic or
haemorrhagic complications and the follow-up was uneventful.
PMID: 11759322 [PubMed - indexed for MEDLINE]
42: J Thorac Cardiovasc Surg 2001 Dec;122(6):1254-5
One-year experience with the platelet glycoprotein IIb/IIIa antagonist tirofiban
and heparin during cardiopulmonary bypass in patients with heparin-induced
thrombocytopenia type II.
Koster A, Meyer O, Fischer T, Kukucka M, Krabatsch T, Bauer M, Kuppe H, Hetzer
R.
Department of Anaesthesiology, Deutsches Herzzentrum Berlin, Berlin, Germany.
koster@dhzb.de
PMID: 11726910 [PubMed - indexed for MEDLINE]
43: Ann Thorac Surg 2001 Nov;72(5):1730-2
Off-pump coronary artery bypass grafting for acute heparin-induced
thrombocytopenia.
Warkentin TE, Dunn GL, Cybulsky IJ.
Department of Pathology and Molecular Medicine, McMaster University, Hamilton,
Ontario, Canada.
Surgical revascularization of coronary arteries is problematic for patients with
heparin-induced thrombocytopenia because the available nonheparin anticoagulants
cannot be reversed pharmacologically. We used three-vessel off-pump coronary
artery bypass grafting in a patient with heparin-induced thrombocytopenia, as it
allowed us to use substantially lower doses of nonheparin anticoagulant
(danaparoid sodium), compared with procedures requiring cardiopulmonary bypass.
PMID: 11722075 [PubMed - indexed for MEDLINE]
44: J Extra Corpor Technol 2001 Sep;33(3):193-6
Some new perspectives in heparin-induced thrombocytopenia type II.
Koster A, Meyer O, Hetzer R, Kuppe H.
Department of Anesthesia, Deutsches Herzzentrum Berlin, Germany. Koster@DHZB.de
We conclude that HIT II is a serious complication, particularly in patients
undergoing cardiovascular surgery that involves CPB. New tests might contribute
to the earlier diagnosis of this disease. However, the reduction of immunization
by the use of alternative anticoagulants whenever possible seems to be the most
effective strategy for the reduction of HIT II-associated complications. If HIT
II is diagnosed. r-hirudin is effective as an acute therapy (especially in
combination with GP IIb/IIIa inhibitors) and also for further anticoagulation.
If patients must undergo CPB, all current alternative anticoagulation concepts
are associated with relevant drawbacks that put the patient at an increased risk
for post-operative bleeding and/or CPB thrombosis. Currently, r-hirudin is most
probably the best option for this purpose. However, when there is impaired renal
function, the persistent anticoagulant effect is associated with hemorrhage.
Further studies must evaluate whether extracorporeal elimination procedures,
such as hemofiltration or plasmapheresis, are effective in avoiding such
complications. Otherwise, the combination of UFH with a potent antiplatelet
agent, especially with short-acting GP IIb/IIIa antagonists, is an attractive
alternative.
Publication Types:
Review
Review, Tutorial
PMID: 11680734 [PubMed - indexed for MEDLINE]
45: Perfusion 2001 Sep;16(5):411-6
Alternatives to unfractionated heparin for anticoagulation in cardiopulmonary
bypass.
von Segesser LK, Mueller X, Marty B, Horisberger J, Corno A.
Department of Cardiovascular Surgery, CHUV, Centre Hospitalier Universitaire
Vaudois, Lausanne, Switzerland. Ludwig.von_Segesser@chuv.hospvd.ch
Despite the progress made in the development of cardiopulmonary bypass (CPB)
equipment, systemic anticoagulation with unfractionated heparin and post-bypass
neutralization with protamine are still used in most perfusion procedures.
However, there are a number of situations where unfractionated heparin,
protamine or both cannot be used for various reasons. Intolerance of protamine
can be addressed with extracorporeal heparin removal devices, perfusion with
(no) low systemic heparinization and, to some degree, by perfusion with
alternative anticoagulants. Various alternative anticoagulation regimens have
been used in cases of intolerance to unfractionated heparin, including extreme
hemodilution, low molecular weight heparins, danaparoid, ancrod, r-hirudin,
abciximab, tirofiban, argatroban and others. In the presence of heparin-induced
thrombocytopenia (HIT) and thrombosis, the use of r-hirudin appears to be an
acceptable solution which has been well studied. The main issue with r-hirudin
is the difficulty in monitoring its activity during CPB, despite the fact that
ecarin coagulation time assessment is now available. A more recent approach is
based on selective blockage of platelet aggregation by means of monoclonal
antibodies directed to GPIIb/IIIa receptors (abciximab) or the use of a
GPIIb/IIIa inhibitor (tirofiban). An 80% blockage of the GPIIb/IIIa receptors
and suppression of platelet aggregation to less than 20% allows the giving of
unfractionated heparin and running CPB in a standard fashion despite HIT and
thrombosis. Likewise, at the end of the procedure, unfractionated heparin is
neutralized with protamine as usual and donor platelets are transfused if
necessary. GPIIb/IIIa inhibitors are frequently used in interventional
cardiology and, therefore, are available in most hospitals.
Publication Types:
Review
Review, Tutorial
PMID: 11565896 [PubMed - indexed for MEDLINE]
46: J Extra Corpor Technol 2001 May;33(2):117-25
Use of ecarin clotting time (ECT) with lepirudin therapy in heparin-induced
thrombocytopenia and cardiopulmonary bypass.
Fabrizio MC.
UPMC Presbyterian Perfusion Services Department, University of Pittsburgh
Medical Center, Pennsylvania 15213, USA. fabriziomc@msx.upmc.edu
Heparin-induced thrombocytopenia (HIT) is described as an allergy-like adverse
reaction to heparin. It is a potentially severe complication of heparin therapy
that can result in serious or life-threatening venous or arterial thromboembolic
events. In the United States, lepirudin (Aventis Pharma AG, Strasbourg, France)
is an approved therapy for anticoagulation in patients with HIT requiring
anticoagulation. Lepirudin is a recombinant form of hirudin, a leech enzyme that
is a highly specific direct inhibitor of thrombin. Lepirudin monitoring during
surgery can be managed with ecarin clotting time (ECT) (Cardiovascular
Diagnostics, Inc., Raleigh, NC), which has recently been approved as a
humanitarian device exemption (HDE) for use in the United States in the
management of HIT with cardiopulmonary bypass. This case report describes a
patient with HIT who was managed successfully with lepirudin and ECT during
coronary artery bypass grafting.
PMID: 11467439 [PubMed - indexed for MEDLINE]
47: Anesth Analg 2001 Jul;93(1):28-32
The relationship between hirudin and activated clotting time: implications for
patients with heparin-induced thrombocytopenia undergoing cardiac surgery.
Despotis GJ, Hogue CW, Saleem R, Bigham M, Skubas N, Apostolidou I, Qayum A,
Joist JH.
Departments of Anesthesiology, Pathology and ImmunologyWashington University
School of Medicine, St. Louis, Missouri 63110, USA.
Anticoagulation with recombinant hirudin (r-hirudin) (Refludan) has been
suggested as an alternative to heparin for patients with heparin-induced
thrombocytopenia requiring cardiac surgery. We sought to develop a modified
activated coagulation time (ACT) that would allow quantification of the levels
of r-hirudin required during cardiopulmonary bypass (CPB). Twenty-one patients
scheduled for elective cardiac surgical procedures requiring CPB were enrolled
in this IRB-approved study. R-hirudin was added to blood specimens obtained
before heparin administration (before CPB) and 30 min after heparin
neutralization with protamine (after CPB) to result in concentrations of 0, 2,
4, 6, 7, or 8 microg/mL. Kaolin/ACT and complete blood count measurements were
assayed in native specimens (first 10 patients, Phase I) or in specimens mixed
with equal volumes of commercial normal plasma (second 11 patients, Phase II).
In Phase I, good (r(2) = 0.83) linear relationships between ACT values and
r-hirudin concentrations (< or =4 microg/mL) were observed in specimens obtained
before CPB. However, ACT values were markedly prolonged (P < 0.0001) by
r-hirudin in specimens obtained after CPB, with ACT values generally exceeding
the ACT's detection limit (>999 s) at hirudin concentrations >2 microg/mL. In
patient specimens mixed with normal plasma (Phase II), ACT/hirudin relationships
(i.e., hirudin/ACT slope values obtained with hirudin concentration < or =4
microg/mL) in the post-CPB period (0.022 +/- 0.004 microg. mL(-1). s(-1)) were
similar (P = 0.47) to those (0.019 +/- 0.004 microg. mL(-1). s(-1)) obtained in
the pre-CPB period. Accordingly, a significant relationship between normal
plasma-supplemented ACT values and predilution hirudin concentration was
obtained in the post-CPB (hirudin = 0.039ACT - 4.34, r(2) = 0.91) period.
Although our data demonstrate that the ACT test cannot be used to monitor
hirudin during CPB, the addition of 50% normal plasma to post-CPB hemodiluted
blood specimens yields a consistent linear relationship between hirudin
concentration and ACT values up to a predilution concentration of 8 microg/mL.
Plasma-modified ACT may be useful in monitoring hirudin anticoagulation during
CPB. Implications: A modified activated clotting time test system that may be
helpful in monitoring hirudin anticoagulation in patients with heparin-induced
thrombocytopenia during cardiac surgery with cardiopulmonary bypass is
described.
Publication Types:
Clinical Trial
PMID: 11429333 [PubMed - indexed for MEDLINE]
48: Ann Thorac Surg 2001 Jun;71(6):1920-4
Heparin-induced thrombocytopenia: bovine versus porcine heparin in
cardiopulmonary bypass surgery.
Konkle BA, Bauer TL, Arepally G, Cines DB, Poncz M, McNulty S, Edie RN, Mannion
JD.
Department of Medicine, Cardeza Foundation for Hematologic Research, Jefferson
Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
konkleb@mail.med.upenn.edu
BACKGROUND: Studies have demonstrated a high incidence of antibodies to
heparin/platelet factor 4 complexes, the antigen in heparin-induced
thrombocytopenia, in patients after cardiopulmonary bypass surgery. In many
hospitals, beef lung heparin has been used historically for cardiopulmonary
bypass, and there has been reluctance to change to porcine heparin despite
concerns of an increased incidence of heparin-induced thrombocytopenia in
patients receiving bovine heparin. METHODS: A prospective randomized trial
comparing bovine and porcine heparin in cardiopulmonary bypass surgery was
conducted. Presurgery and postsurgery heparin antibody formation was studied
using the serotonin release assay and a heparin/platelet factor 4 enzyme-linked
immunosorbent assay. RESULTS: Data available on 98 patients, randomized to
receive either bovine or porcine heparin, revealed no significant difference in
patient positivity by serotonin release assay (12% in both groups) or by the
heparin/platelet factor 4 enzyme-linked immunosorbent assay (29% with porcine
and 35% with bovine heparin) postoperatively. There were no significant
differences between preoperative and postoperative platelet counts or
thromboembolic complications. CONCLUSIONS: Our study does not support the belief
that bovine heparin is more likely than porcine heparin to induce the
development of antibodies to heparin/platelet factor 4.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 11426769 [PubMed - indexed for MEDLINE]
49: Swiss Surg 2001;7(3):141-4
[Challenging perioperative anticoagulation in a patient with Budd-Chiari
syndrome and heparin-induced thrombocytopenia]
[Article in German]
Gygax E, Berdat P, Carrel T.
Universitatsklinik fur Herz- und Gefasschirurgie, Inselspital Bern.
We report on a patient suffering from Budd-Chiari disease who developed
heparin-induced thrombocytopenia preoperatively. Dorsocranial liver resection
and hepatoatrial anastomosis were performed with the extracorporeal circulation
and perioperative anticoagulation was achieved with r-hirudin. Surprisingly,
thrombus formation was observed in the venous reservoir although intraoperative
anticoagulation values were within the targeted level. An additional bolus of
hirudin and rinsing the reservoir allowed unproblematic discontinuation of the
cardiopulmonary bypass.
PMID: 11407043 [PubMed - indexed for MEDLINE]
50: Eur J Cardiothorac Surg 2001 Apr;19(4):525-7
Budd--Chiari syndrome and heparin-induced thrombocytopenia.
Carrel T, Berdat P, Schmidli J, Gygax E.
Clinic for Cardiovascular Surgery, University Hospital, CH-3010 Berne,
Switzerland. thierry.carrel@insel.ch
We report on a patient suffering from Budd--Chiari disease who developed
heparin-induced thrombocytopenia preoperatively. Dorsocranial liver resection
and hepatoatrial anastomosis were performed with the extracorporeal circulation
and perioperative anticoagulation was achieved with r-hirudin. Surprisingly,
thrombus formation was observed in the venous reservoir although ACT was 590 s
and aPTT 55 s. An additional bolus of hirudin and rinsing the reservoir allowed
unproblematic discontinuation of the cardiopulmonary bypass.
PMID: 11306328 [PubMed - indexed for MEDLINE]
51: Ann Thorac Surg 2001 Mar;71(3):1041-2
Emergency cardiopulmonary bypass in a bilaterally nephrectomized patient with a
history of heparin-induced thrombocytopenia: successful reexposure to heparin.
Selleng S, Lubenow N, Wollert HG, Mullejans B, Greinacher A.
Department of Anesthesiology and Critical Care, Heart and Diabetes Centre
Mecklenburg-Vorpommern, Karlsburg, Germany.
We present a case of emergency coronary artery bypass surgery in a bilaterally
nephrectomized patient with a history of heparin-induced thrombocytopenia. The
patient was reexposed short term to heparin during cardiopulmonary bypass and
did not develop any complications related to heparin-induced thrombocytopenia.
Despite intraoperative neutralization of heparin severe bleeding complications
occurred, probably resulting from preoperative therapeutic anticoagulation with
rhirudin in conjunction with an increased half-life of more than 2 days.
PMID: 11269430 [PubMed - indexed for MEDLINE]
52: Arch Mal Coeur Vaiss 2001 Feb;94(2):144-7
[Use of Organon, a synthetic heparinoid, in two cardiopulmonary bypass
procedures in the same patient sensitive to heparin]
[Article in French]
Pineau E, Le Bret E, Folliguet T, Saint Maurice OS, Carbognani D, Laborde F.
Departement cardiovasculaire, Institut mutualiste Montsouris, 42, boulevard
Jourdan, 75674 Paris.
We report the case of a patient who underwent two cardiopulmonary bypass (CPB)
procedures with Orgaran because of heparin-induced thrombocytopenia. A 38
years-old man with ischemic mitral insufficiency was operated for coronary
artery bypass and valvular replacement. The CPB was carried out with heparin.
Heparin-induced thrombocytopenia occured and was proven immunologically. Two
months later, a new valvular replacement was performed because of paravalvular
leak due to endocarditis. The Orgaran-CPB protocol was as follows: 5,000 units
before cardiopulmonary bypass, 5,000 units in the priming volume, anti-Xa level
between 0.9 and 1.1 units/mL, with injection of 1,500 units if necessary, no
administration of protamine. One month later, a new valvular replacement was
necessary and performed with the same protocol using Orgaran. No bleeding or
thrombotic complication occurred. Orgaran is a safe and reliable anti-thrombotic
substitute if anti-Xa activity is closely monitored.
Publication Types:
Review
Review of Reported Cases
PMID: 11265553 [PubMed - indexed for MEDLINE]
53: Ann Thorac Surg 2001 Feb;71(2):678-83
Cardiac surgery with cardiopulmonary bypass in patients with type II
heparin-induced thrombocytopenia.
Aouifi A, Blanc P, Piriou V, Bastien OH, Ffrench P, Hanss M, Lehot JJ.
Service d'Anesthesie--Reanimation and EA 1896, Universite Claude Bernard Lyon I,
France. a.aouifi@free.fr
BACKGROUND: The use of cardiopulmonary bypass (CPB) in patients with a history
of type II heparin-induced thrombocytopenia (HIT) may be associated with
complications related to their anticoagulation management. METHODS: Between
January 1997 and December 1999, among 4,850 adults patients who underwent
cardiac surgery in our institution, 10 patients presented with preoperative type
II HIT. In 4 patients, anticoagulation during CPB was achieved with danaparoid
sodium. In 6 other patients, heparin sodium was used after pretreatment with
epoprostenol sodium. RESULTS: No significant change in platelet count occurred
in any patient. No intraoperative thrombotic complication was encountered. Total
postoperative chest drainage ranged from 250 to 1,100 ml in patients pretreated
with epoprostenol and 1,700 to 2,470 ml in patients who received danaparoid
sodium during CPB (p < 0.05, Mann-Whitney U test). CONCLUSIONS: During CPB,
inhibition of platelet aggregation by prostacyclin may be a safe anticoagulation
approach in patients with type II HIT.
PMID: 11235727 [PubMed - indexed for MEDLINE]
54: N Engl J Med 2000 Dec 28;343(26):1973
Comment on:
N Engl J Med. 2000 Aug 17;343(7):515.
Heparin-induced thrombocytopenia and cardiopulmonary bypass.
Nash I.
Publication Types:
Comment
Letter
PMID: 11186681 [PubMed - indexed for MEDLINE]
55: Anesthesiology 2001 Feb;94(2):245-51
Anticoagulation during cardiopulmonary bypass in patients with heparin-induced
thrombocytopenia type II and renal impairment using heparin and the platelet
glycoprotein IIb-IIIa antagonist tirofiban.
Koster A, Kukucka M, Bach F, Meyer O, Fischer T, Mertzlufft F, Loebe M, Hetzer
R, Kuppe H.
Department of Anesthesia, Deutsches Herzzentrum Berlin, Berlin Germany.
koster@dhzb.de
BACKGROUND: Patients with heparin-induced thrombocytopenia type II require an
alternative to standard heparin anticoagulation. However, in patients with renal
impairment, anticoagulation during cardiopulmonary bypass with agents such as
danaparoid sodium or r-hirudin are associated with hemorrhage. Anticoagulation
with unfractionated heparins combined with prostacyclin, a potent platelet
aggregation inhibitor, is associated with severe hypotension. The authors
investigated a new concept using unfractionated heparins after platelet
inhibition with the short-acting platelet glycoprotein IIb-IIIa antagonist
tirofiban. METHODS: Ten patients with heparin-induced thrombocytopenia type II
and renal impairment were enrolled in the investigation. All had heparin-induced
thrombocytopenia type II antibodies present as proved by the heparin-induced
platelet aggregation assay, the heparin-platelet factor 4 enzyme-linked
immunosorbent assay, or both. In all patients, preoperative anticoagulation to
an activated partial thromboplastin time of 40-60 s was performed with
r-hirudin. Anticoagulation during cardiopulmonary bypass was achieved with a
bolus of 400 IU/kg unfractionated heparins after a bolus of tirofiban 10
microg/kg followed by an infusion of tirofiban at a rate of 0.15 microg x kg(-1)
x min(-1) until 1 h before conclusion of cardiopulmonary bypass. Additional
unfractionated heparins were only administered if activated clotting time
decreased below 480 s. Coagulation was monitored by a abciximab-modified TEG and
the adenosine diphosphate-stimulated (20 microm) platelet aggregometry. D-dimer
concentrations, as a marker of venous thromboembolism, were measured before and
12, 24, and 48 h after surgery. Postoperative antithrombotic therapy was started
immediately with r-hirudin to anticoagulation to an activated partial
thromboplastin time of 40-60 s. RESULTS: The postoperative blood loss ranged
from 110 to 520 ml. No patient needed reexploration. In no patient was there
clinical evidence of thrombosis or embolism in the postoperative period or of a
critical increase of the D-dimer concentrations, suggesting venous
thromboembolism. Transfusion of platelets was necessary in only two patients.
CONCLUSIONS: The protocol is easy to perform and no increased postoperative
bleeding and no thromboembolic complications occurred. The combination of
unfractionated heparins and tirofiban may be an alternative to other
anticoagulation strategies in patients with heparin-induced thrombocytopenia.
PMID: 11176088 [PubMed - indexed for MEDLINE]
56: Ann Thorac Surg 2000 Dec;70(6):2173-81
Cardiopulmonary bypass in patients with heparin-induced thrombocytopenia and
thrombosis.
Follis F, Schmidt CA.
Department of Cardiothoracic Surgery, University of New Mexico Health Sciences
Center, Albuquerque, USA. follis99@hotmail.com
Heparin-induced thrombocytopenia and thrombosis (HITT) is an immunomediated
disorder induced by the administration of heparin for therapeutic purposes. The
presence of this condition in patients requiring full heparinization for
cardiopulmonary bypass constitutes a formidable challenge for the cardiac
surgeon. In this review, the clinical and experimental experience described in
the literature are discussed in the perspective of the normal coagulation and
the pathophysiology of HITT and in the light of a variety of old and new
alternative anticoagulants.
Publication Types:
Review
Review of Reported Cases
PMID: 11156153 [PubMed - indexed for MEDLINE]
57: Ann Thorac Surg 2000 Dec;70(6):2160-1
Cardiopulmonary bypass in a patient with heparin-induced thrombocytopenia II and
impaired renal function using heparin and the platelet GP IIb/IIIa inhibitor
tirofiban as anticoagulant.
Koster A, Loebe M, Mertzlufft F, Kuppe H, Hetzer R.
Department of Anesthesia, Deutsches Herzzentrum Berlin. koster@dhzb.de
In a patient with heparin-induced thrombocytopenia II and impaired renal
function, anticoagulation during cardiopulmonary bypass was successfully
performed by the use of unfractionated heparin and the platelet glycoprotein
IIb/IIIa inhibitor tirofiban. Postoperative antithrombotic therapy with
recombinant hirudin was immediately initiated. This regimen for anticoagulation
for cardiopulmonary bypass in patients with heparin-induced thrombocytopenia II
appears to be particularly appropriate for patients with impaired renal function
or for hospitals without special experience with other alternative
anticoagulation strategies.
PMID: 11156147 [PubMed - indexed for MEDLINE]
58: J Cardiothorac Vasc Anesth 2000 Dec;14(6):707-9
Use of danaparoid during cardiopulmonary bypass in patients with heparin-induced
thrombocytopenia.
Olin DA, Urdaneta F, Lobato EB.
Department of Anesthesiology, University of Florida College of Medicine, and the
Gainesville Veterans Affairs Medical Center, USA.
PMID: 11139115 [PubMed - indexed for MEDLINE]
59: Perfusion 2000 Nov;15(6):531-9
Use of danaparoid sodium (Orgaran) as an alternative to heparin sodium during
cardiopulmonary bypass: a clinical evaluation of six cases.
Fernandes P, Mayer R, MacDonald JL, Cleland AG, Hay-McKay C.
Clinical Perfusion Services, London Health Sciences Centre, Ontario, Canada.
philip.fernandes@lhsc.on.ca
Heparin-induced thrombocytopenia (HIT) has become more prevalent in today's
cardiac setting and has resulted in the need for alternative anticoagulant
therapies. Danaparoid sodium, one alternative to heparin, has been used in six
cardiopulmonary bypass procedures in this hospital. This clinical experience has
resulted in the progressive refinement of a protocol for the 'safe' clinical use
of danaparoid sodium. Although there were six positive outcomes with the use of
danaparoid sodium, alternatives must be explored in order to find the optimal
anticoagulant for the treatment of HIT.
PMID: 11131218 [PubMed - indexed for MEDLINE]
60: Ann Thorac Surg 2000 Oct;70(4):1434-43
Cardiopulmonary bypass in humans: bypassing unfractionated heparin.
Frederiksen JW.
Department of Surgery, Northwestern University Medical School, Chicago, Illinois
60611, USA. jwf@nwu.edu
Seven anticoagulants besides unfractionated heparin have been used for human
cardiopulmonary bypass (CPB), mainly in patients with heparin-induced
thrombocytopenia. The collective experience with these alternative
anticoagulants provides a perspective on current efforts aimed at improving CPB
anticoagulation. Unfortunately, each alternative currently lacks a standard
dosing schedule and a reliable method of monitoring the adequacy of its
anticoagulant effect during CPB. Most also lack proven antidotes. Thus,
unfractionated heparin remains the anticoagulant of choice for standard CPB.
Publication Types:
Review
Review, Tutorial
PMID: 11081925 [PubMed - indexed for MEDLINE]
61: Acta Anaesthesiol Scand 2000 Sep;44(8):991-3
Comment in:
Acta Anaesthesiol Scand. 2001 May;45(5):655.
Heparin-induced thrombocytopenia thrombosis after cardiac surgery. A case
report.
Antoniou T, Stavridis G, Daganou M, Melissari E, Gatzonis S.
Department ofAnesthesia and Surgery, Onassis Cardiac Surgery Center, Athens,
Greece.
We report a rare case of cerebral infarct resulting in brain death due to
heparin-induced thrombocytopenia thrombosis (HITT), manifested in the immediate
postoperative period following aortic valve replacement in a 46-year-old woman
whose only prior exposure to heparin was during catheterization four months
prior to surgery. The diagnosis of HITT was suspected after a significant
decrease of the platelet count and it was confirmed by a heparin-induced
platelet activation assay showing platelet aggregation in the presence of
heparin.
PMID: 10981578 [PubMed - indexed for MEDLINE]
62: J Heart Lung Transplant 2000 Aug;19(8):810-4
Management strategies for heparin-induced thrombocytopenia in heart-transplant
candidates: case report and review of the literature.
Pamboukian SV, Ignaszewski AP, Ross HJ.
Cardiac Transplant and Heart Failure fellow,a Rush Presbyterian St. Luke's
Medical Center, Chicago, Illinois, USA.
Management of anticoagulation in patients with heparin-induced thrombocytopenia
(HIT) undergoing surgery requiring cardiopulmonary bypass (CPB), such as cardiac
transplantation, represents a difficult clinical problem and no clear management
strategy exists. The cases of 2 patients with HIT who underwent cardiac
transplantation using differing anticoagulation strategies are presented with a
discussion of potential advantages and pitfalls of each approach used.
PMID: 10967277 [PubMed - indexed for MEDLINE]
63: N Engl J Med 2000 Aug 17;343(7):515
Comment in:
N Engl J Med. 2000 Dec 28;343(26):1973.
Use of heparin during cardiopulmonary bypass in patients with a history of
heparin-induced thrombocytopenia.
Potzsch B, Klovekorn WP, Madlener K.
Publication Types:
Letter
PMID: 10950681 [PubMed - indexed for MEDLINE]
64: J Thorac Cardiovasc Surg 2000 Aug;120(2):428-9
Cardiopulmonary bypass and heparin-induced thrombocytopenia: pitfalls of
anticoagulation with danaparoid.
Kanagasabay R, Unsworth-White MJ, Farnsworth G, Haxby EJ, Smith EE.
Publication Types:
Letter
PMID: 10917979 [PubMed - indexed for MEDLINE]
65: J Extra Corpor Technol 1999 Dec;31(4):211-5
The emergency use of recombinant hirudin in cardiopulmonary bypass.
Johnston N, Jessen ME, DiMaio M, Douglass DS.
Division of Thoracic and Cardiovascular Surgery, University of Texas
Southwestern Medical Center at Dallas 75235-88679, USA.
The most common anticoagulant used for cardiopulmonary bypass is heparin. An
alternate form of anticoagulant therapy is needed for patients who have
immune-mediated heparin-associated thrombocytopenia (HIT). Thrombocytopenia
causes bleeding and may lead to serious arterial and venous thrombosis. HIT or
heparin-induced thrombocytopenia with thrombosis type II (HITT) are both
described as adverse reactions to heparin. They are diagnosed with a platelet
count less than a 100,000/mcl for 2 consecutive days. HITT, the severe form, is
characterized with the thrombocytopenia in combination with thromboembolic
complications, such as strokes, myocardial infarctions, and limb ischemia. Two
cases are presented in which r-hirudin was used for anticoagulation for
aortocoronary bypass surgery and mitral valve replacement. The activated partial
prothrombin time (aPTT) was used to monitor coagulation. In the first case, the
aPTT was maintained greater than 100 seconds, and at the termination of
cardiopulmonary bypass, some clot was noted in the cardiopulmonary bypass
circuit. In the second case, a longer cardiopulmonary bypass run was
anticipated, the hirudin bolus and infusion rate were increased, and the aPTT
was maintained at greater than 200 sec. Adequate coagulation resulted, and, at
the end of bypass, no clot was noted. These case studies seem to suggest a
higher dosage of r-hirudin may be required for the use of cardiopulmonary bypass
and a need to maintain aPTT values greater than 200 sec to help monitor
anticoagulation.
PMID: 10915479 [PubMed - indexed for MEDLINE]
66: Anesth Analg 2000 Aug;91(2):265-9
Elimination of recombinant hirudin by modified ultrafiltration during simulated
cardiopulmonary bypass: assessment of different filter systems.
Koster A, Merkle F, Hansen R, Loebe M, Kuppe H, Hetzer R, Crystal GJ, Mertzlufft
F.
Department of Anesthesiology, Deutsches Herzzentrum, Berlin, Germany.
Recombinant hirudin (r-hirudin) is being used increasingly in patients with
heparin-induced thrombocytopenia type II. Renal failure has been demonstrated to
prolong the half-life of r-hirudin and to cause bleeding in patients who have
undergone cardiopulmonary bypass (CPB). We assessed the ability of different
filter systems for modified ultrafiltration to eliminate r-hirudin in vitro
using simulated CPB. r-Hirudin concentration was measured (chromogenic
laboratory standard plus ecarin clotting time) before and after filtration, and
its elimination was calculated using both controlled system flow and arterial
inflow (separate pump). Four hemofilters (Renoflow II, Baxter; Arylane H4, Cobe;
Ultraflux AV 600, Fresenius; and BCS 110 Plus, Iostra) and two plasmapheresis
filter systems (ASAHI Plasmaflow OP, Diamed; and PF 2000 N, Gambro) were
assessed (5 filters of each brand = 30 filters) in a closed in vitro CPB system
applying conditions usually occurring during CPB. Ten plasmapheresis filters
showed a greater ability than 20 hemofilters to eliminate r-hirudin (60%-70% vs
15%-42%) within the shortest time (80 vs 180 s). Among the four hemofilter
systems, the Arylane H4 filter provided the most effective (42%) r-hirudin
elimination. Elimination of r-hirudin was markedly improved using plasmapheresis
systems, compared with hemofilter systems. Our findings may be relevant to
patients with impaired renal function, who have been administered r-hirudin
during CPB. Implications: Modified ultrafiltration may enhance the elimination
of recombinant-hirudin, although plasmapheresis systems provide the most rapid
and complete elimination of recombinant-hirudin during simulated cardiopulmonary
bypass. The decision to use a specific system will ultimately depend on the
prevailing clinical situation and overall health of the patient.
PMID: 10910829 [PubMed - indexed for MEDLINE]
67: Schweiz Med Wochenschr 2000 Jun 10;130(23):896-9
[R-hirudin (lepirudin, refludan) as an alternative anticoagulant in
heparin-induced thrombocytopenia during cardiopulmonary bypass connection]
[Article in German]
Shah AC, Genoni M, Niederhauser U, Maloigne M, Turina M.
Abteilung fur Herzchirurgie, Stadtspital Triemli, Zurich.
A 72-year-old patient with heparin-induced thrombocytopenia (HIT) and global
cardiac decompensation underwent cardiac surgery using an extracorporeal circuit
(ECC). For systemic anticoagulation r-Hirudin (lepirudin, Refludan) was
administered as a heparin substitute during extracorporeal circuit. During
cardiopulmonary bypass (100 min) the concentration of r-Hirudin was between 2.9
and 4.6 mcg/ml under continuous infusion of r-Hirudin at between 1.5 and 4.5
mcg/kg/min. The operation was successful and during its course no abnormal
bleeding or fibrin formation in the extracorporeal circuit was observed. One
hour after operation haemorrhage occurred and rethoracotomy was performed
without discovering the cause of the surgical bleeding. After substitution with
fresh frozen plasma, thrombocytes and Prothromblex the bleeding stopped on the
operation day. The further postoperative course was uncomplicated. After 3 days
the patient came to nursing station and was discharged from hospital to a
rehabilitation centre after 13 days. After a further 3 weeks he went home in a
good general condition.
PMID: 10897491 [PubMed - indexed for MEDLINE]
68: Ann Thorac Surg 2000 Jun;69(6):1942-3
Use of recombinant-hirudin in pulmonary thromboendarterectomy.
Rubens FD, Sabloff M, Wells PS, Bourke M.
Department of Surgery, University of Ottawa, Ontario, Canada.
frubens@ottawaheart.ca
A patient with chronic thromboembolic pulmonary hypertension and heparin-induced
thrombocytopenia successfully underwent pulmonary thromboendarterectomy with
circulatory arrest, using recombinant hirudin as an alternative anticoagulant to
heparin. Techniques for administration as well as monitoring of this drug's
effects are discussed.
PMID: 10892957 [PubMed - indexed for MEDLINE]
69: J Cardiothorac Vasc Anesth 2000 Jun;14(3):304-8
Management of urgent high-risk cardiopulmonary bypass in patients with
heparin-induced thrombocytopenia type II and coexisting disorders of renal
function: use of heparin and epoprostenol combined with on-line monitoring of
platelet function.
Mertzlufft F, Kuppe H, Koster A.
Department of Anesthesiology and Critical Care Medicine, Universitaetskliniken
des Saarlandes, Homburg-Saar, Germany.
PMID: 10890486 [PubMed - indexed for MEDLINE]
70: J Cardiothorac Vasc Anesth 2000 Jun;14(3):300-3
Acute heparin-induced thrombocytopenia type II during cardiopulmonary bypass.
Koster A, Crystal GJ, Kuppe H, Mertzlufft F.
Department of Anesthesia, German Heart Institute Berlin.
PMID: 10890485 [PubMed - indexed for MEDLINE]
71: J Cardiothorac Vasc Anesth 2000 Jun;14(3):249-52
Hirudin monitoring using the TAS ecarin clotting time in patients with
heparin-induced thrombocytopenia type II.
Koster A, Hansen R, Grauhan O, Hausmann H, Bauer M, Hetzer R, Kuppe H,
Mertzlufft F.
Department of Anaesthesiology, Deutsches Herzzentrum, Charite, Berlin, Germany.
OBJECTIVE: To assess the reliability of the TAS/ecarin clotting time (ECT) for
on-line monitoring of r-hirudin in cardiovascular surgery with and without
cardiopulmonary bypass (CPB). DESIGN: Samples were spiked with r-hirudin (0 to 5
microg/mL) and calibration curves constructed. Reproducibility was evaluated by
measurement of the sample five times at each concentration. The influence of
variations in hematocrit, plasma factors, and platelet count on the test results
was examined. Samples were obtained from patients during cardiovascular surgery
with CPB (n = 8), without CPB (n = 3), and from volunteers (n = 5) and compared
with the laboratory reference tests. All tests were performed in duplicate.
SETTING: Deutsches Herzzentrum Berlin. PARTICIPANTS: Five healthy volunteers and
11 patients undergoing cardiovascular surgery. INTERVENTIONS: None. MEASUREMENTS
AND MAIN RESULTS: The TAS/ECT showed linearity and reliability to an r-hirudin
concentration of 5 microg/mL and was not influenced (p < 0.005) by the varying
conditions of the in vitro setup. The correlation to the laboratory method was
0.74 for the CPB group and 0.87 for the non-CPB group. CONCLUSIONS: The TAS/ECT
is a reliable assay for monitoring r-hirudin at the point of care. With this
information, the use of r-hirudin during surgery or angioplasty should become
more effective and safer.
PMID: 10890474 [PubMed - indexed for MEDLINE]
72: J Cardiothorac Vasc Anesth 2000 Jun;14(3):243-8
Recombinant hirudin as an alternative for anticoagulation during cardiopulmonary
bypass in patients with heparin-induced thrombocytopenia type II: a 1-year
experience in 57 patients.
Koster A, Hansen R, Kuppe H, Hetzer R, Crystal GJ, Mertzlufft F.
Department of Anesthesiology, German Heart Center, Charite, Berlin.
OBJECTIVE: To explore the possible use of recombinant hirudin (r-hirudin) as an
alternative to heparin for anticoagulation during cardiovascular surgery.
DESIGN: Retrospective analysis. SETTING: Two university hospitals. PARTICIPANTS:
Fifty-seven patients with heparin-induced thrombocytopenia type II (HIT II) in
whom r-hirudin was used during cardiovascular surgery with cardiopulmonary
bypass (CPB). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The r-hirudin
concentration was monitored on-line, at the point of the patient's care using
the ecarin clotting time and maintained in the range of 3 to 4 microg/mL. The
r-hirudin elimination at the conclusion of CPB was augmented through modified
zero-balanced ultrafiltration and forced diuresis. The duration of CPB was 63 to
246 minutes. The r-hirudin requirement per minute of CPB was 0.016 to 0.035
microg/kg/min, and the 24-hour blood drainage was 50 to 2,200 mL. Of the 57
patients, 54 fully recovered, including 9 patients who did not require any
allogenic products. Four patients, all with impaired renal function, showed
prolonged r-hirudin elimination and excessive bleeding and required surgical
reexploration. Three patients died as a result of complications unrelated to the
perioperative management. CONCLUSION: This study provides evidence that
r-hirudin can be used safely and effectively for routine anticoagulation during
CPB in patients diagnosed with HIT II. Almost 95% of the patients in whom it was
used were discharged uneventfully. Patients with perioperative renal failure,
however, showed increased bleeding.
PMID: 10890473 [PubMed - indexed for MEDLINE]
73: Am J Crit Care 2000 Jul;9(4):276-8
Heparin-induced thrombocytopenia and thrombosis syndrome after cardiopulmonary
bypass.
Holmes-Ghosh E.
Department of Cardiothoracic Surgery, Hahnemann University Hospital,
Philadelphia, PA, USA.
Publication Types:
Review
Review, Tutorial
PMID: 10888150 [PubMed - indexed for MEDLINE]
74: J Heart Lung Transplant 2000 May;19(5):510-2
Comment on:
J Heart Lung Transplant. 1998 Jul;17(7):729-31.
Heparin in patients with heparin-induced thrombocytopenia type II requiring LVAD
implantation and cardiac transplantation.
Christiansen S, Hammel D, Schmidt C, Scheld HH.
Publication Types:
Comment
Letter
PMID: 10877545 [PubMed - indexed for MEDLINE]
75: Eur J Cardiothorac Surg 2000 Jun;17(6):760-2
Undergoing cardiopulmonary bypass using enoxaparin only during a cardiac
transplantation procedure.
Prifti E, Bonacchi M, Leacche M, Miraldi F.
Istituto di Chirurgia Toracica, Cardiovascolare e Technologie Biomediche,
Universita degli Studi di Siena, Siena, Italy. edvinprifti@hotmail.com
The use of enoxaparin as a replacement drug to standard heparin, for
anticoagulation during extracorporeal circulation, in patients with
heparin-induced thrombocytopenia, is still very limited. Enoxaparin
significantly reduces thrombin formation and activity during cardiopulmonary
bypass. The prolonged circulating rate, slow elimination rate and non-total
reversion of enoxaparin by protamine can induce important postoperative
bleeding. We are describing the first case of cardiac transplantation where
enoxaparin was used as a replacement drug to standard heparin.
PMID: 10856875 [PubMed - indexed for MEDLINE]
76: J Extra Corpor Technol 1999 Sep;31(3):142-4
Heparin-bonded circuit with low systemic anticoagulation in a patient with
heparin-induced thrombocytopenia: a case report.
O'Gara PJ, Aldea GS, Shemin RJ, Shapira OM.
Department of Cardiothoracic Surgery, Boston Medical Center, MA 02118, USA.
paul.ogara@bmc.org
Heparin-induced thrombocytopenia (HIT) in patients undergoing open heart surgery
has been reported with increasing frequency. Several strategies have been
suggested to approach this difficult problem. However, the syndrome is still
associated with significant morbidity and mortality. We describe an 82-year-old
male with HIT who underwent coronary artery bypass grafting utilizing a
heparin-bonded cardiopulmonary bypass circuit with very low systemic
anticoagulation. Only one unit of packed red blood cells was transfused. The
patient recovered uneventfully. This strategy is safe and effective, and,
therefore, should be considered in patients with HIT.
PMID: 10847957 [PubMed - indexed for MEDLINE]
77: J Thorac Cardiovasc Surg 2000 Jun;119(6):1278-83
A quick assay for monitoring recombinant hirudin during cardiopulmonary bypass
in patients with heparin-induced thrombocytopenia type II : adaptation of the
ecarin clotting time to the act II device.
Koster A, Loebe M, Hansen R, Bauer M, Mertzlufft F, Kuppe H, Hetzer R.
Department of Anesthesiology, Deutsches Herzzentrum Berlin, Germany.
koster@dhzb.de
BACKGROUND: Recombinant hirudin is increasingly advocated as a promising
alternative anticoagulation for patients with heparin-induced thrombocytopenia
type II during cardiopulmonary bypass. This requires monitoring of the ecarin
clotting time. No commercial ecarin clotting time assay is available for
clinical use. We adapted the ecarin clotting time to the easy-to-handle ACT II
device. METHODS: Three different concentrations of the ecarin reagent (20, 10, 5
U/mL) were investigated as preliminary studies. Standard calibration curves were
constructed for concentrations of recombinant hirudin ranging from 0 to 5
microgram/mL. In vivo samples were collected from patients with heparin-induced
thrombocytopenia type II who underwent cardiopulmonary bypass, and the values
were compared with the values obtained by the chromogenic method. The final
concentration for the assay of 5 IU/mL ecarin was further assessed in vitro for
reproducibility and the influence of variations in hematocrit, platelet count,
and procoagulants. RESULTS: All three concentrations of ecarin revealed
linearity to 5 microgram/mL concentrations of recombinant hirudin. The ecarin
concentration of 5 U/mL revealed the best correlation (0.87) to the laboratory
method, was reproducible over the whole recombinant hirudin range, and was not
influenced by the variations in the in vitro setup. CONCLUSIONS: The ACT
II/ecarin clotting time with an ecarin concentration of 5 U/mL is a simple and
reliable assay for monitoring recombinant hirudin during cardiopulmonary bypass.
Use of this assay allows a wider use of recombinant hirudin in patients with
heparin-induced thrombocytopenia type II during bypass and thereby may
contribute to the safer management of these patients.
PMID: 10838548 [PubMed - indexed for MEDLINE]
78: Can J Anaesth 2000 Mar;47(3):255-60
Recombinant hirudin anticoagulation for aortic valve replacement in
heparin-induced thrombocytopenia.
Longrois D, de Maistre E, Bischoff N, Dopff C, Meistelman C, Angioi M, Lecompte
T.
Department of Anesthesia and Intensive Care, CHU Nancy-Brabois,
Vandoeuvre-les-Nancy, France. d.longrois@chu-nancy.fr
PURPOSE: To report the case of a patient with HIT that received a prolonged
infusion of r-hirudin (lepirudin; Refludan; Hoechst, France) before, during and
after cardiopulmonary bypass (CPB) for aortic surgery. Although administration
of r-hirudin for CPB anticoagulation has previously been reported, many
questions persist concerning the best therapeutic regimen for CPB
anticoagulation as well as the time of onset and the doses for postoperative
anticoagulation. CLINICAL FEATURES: A 65-yr-old man was admitted for surgery of
aortic stenosis after an episode of acute pulmonary edema complicated by deep
venous thrombosis in the context of documented HIT. The patient received
r-hirudin for 13 dy before surgery at doses (0.4 mg x kg(-1) bolus followed by
0.15 mg x kg(-1) x hr(-1) continuous infusion) that maintained activated partial
thromboplastin time (aPTT) ratios between 2 and 2.5. Anticoagulation for CPB was
performed with r-hirudin given as 0.1 mg x kg(-1) i.v. bolus and 0.2 mg kg(-1)
in the CPB priming volume. Anticoagulation during CPB was monitored with the
whole blood activated coagulation time and ecarin clotting time (ECT) performed
in the operating room with values corresponding to r-hirudin concentrations >5
microg x ml(-1) during CPB. Anticoagulation during CPB was uneventful. Two
bleeding episodes, related to the r-hirudin regimen and necessitating allogeneic
blood transfusion, occurred after surgery. CONCLUSION: This case report confirms
previous experience of the use of r-hirudin for anticoagulation during CPB and
provides additional information in the context of prolonged r-hirudin infusion
before and after CPB.
PMID: 10730738 [PubMed - indexed for MEDLINE]
79: Ann Thorac Surg 2000 Jan;69(1):37-41
Hirudin as anticoagulant for cardiopulmonary bypass: importance of preoperative
renal function.
Koster A, Pasic M, Bauer M, Kuppe H, Hetzer R.
Deutsches Herzzentrum Berlin, Germany.
BACKGROUND: Recombinant hirudin is an alternative anticoagulant for
cardiopulmonary bypass in patients with heparin-induced thrombocytopenia type
II. Although there is no neutralizing agent for recombinant hirudin, its fast
renal elimination enables quick cessation of bleeding after cardiopulmonary
bypass. The aim of the study was to compare anticoagulant effects of recombinant
hirudin in regards to renal function in patients with heparin-induced
thrombocytopenia type II. METHODS: Twenty-one patients (mean age, 65 years, and
range, 35 to 82 years) underwent different complex cardiovascular procedures
using recombinant hirudin as the anticoagulant for cardiopulmonary bypass.
Postoperative blood loss, transfusion requirements, and hemostatic variables
were compared between patients with a creatinine level lower than 1.5 mg/dL
(group 1, normal renal function; n = 17 patients) and those with a creatinine
level greater than 1.5 mg/dL (group 2, impaired renal function; n = 4 patients).
RESULTS: The patients in group 1 showed no increased tendency toward
postoperative bleeding. In contrast, all 4 patients in group 2 required
reexploration for increased postoperative bleeding. They had higher activated
partial thromboplastin times and transfusion requirements postoperatively.
CONCLUSIONS: If recombinant hirudin is used as the anticoagulant for
cardiopulmonary bypass in patients with heparin-induced thrombocytopenia type II
and impaired renal function, the risk of postoperative bleeding is increased.
PMID: 10654482 [PubMed - indexed for MEDLINE]
80: Anesth Analg 2000 Feb;90(2):292-8
Cardiovascular surgery without cardiopulmonary bypass in patients with
heparin-induced thrombocytopenia type II using anticoagulation with recombinant
hirudin.
Koster A, Kuppe H, Crystal GJ, Mertzlufft F.
Department of Anesthesiology, German Heart Center, Berlin, Germany.
PMID: 10648309 [PubMed - indexed for MEDLINE]
81: Anesthesiology 2000 Jan;92(1):263-6
Comment in:
Anesthesiology. 2000 Dec;93(6):1551-2.
Use of recombinant hirudin in patients with heparin-induced thrombocytopenia
with thrombosis requiring cardiopulmonary bypass.
Latham P, Revelis AF, Joshi GP, DiMaio JM, Jessen ME.
Department of Anesthesiology and Pain Management, University of Texas
Southwestern Medical Center at Dallas, 75235-9068, USA.
PMID: 10638925 [PubMed - indexed for MEDLINE]
82: Anaesthesist 1999 Nov;48(11):771-85
Comment in:
Anaesthesist. 1999 Nov;48(11):769-70.
[Heparin-induced thrombocytopenia (HIT). Importance for anesthesia and intensive
care]
[Article in German]
Kleinschmidt S, Seyfert UT.
Klinik fur Anaesthesiologie und Intensivmedizin, Universitatskliniken des
Saarlandes, Homburg/Saar. aiskle@med-rz.uni-sb.de
For many decades, heparins have been used successfully for prophylaxis and
treatment of thromboembolic complications world-wide. Although heparin-induced
thrombocytopenia (HIT Type II) is a well-known adverse effect of heparin
therapy, thromboembolic complications during heparin therapy are rarely
diagnosed exactly to be related to HIT. At present an immunologic etiology of
HIT by generation of multimodal immune complexes against a neo antigen of
heparin and platelet factor 4 is equivocally accepted. The incidence of HIT
seems to be related to the type of heparin (unfractioned/low molecular weight)
or other underlying risks such as peripheral occlusive vessel disease. Mortality
and complications resulting from HIT is reported to be about 20-30% each. For
diagnosis of HIT Type II, clinical observation and simultaneous laboratory
testing are essential. Discontinuation of heparin is a simple and essential
manoeuvre, and anticoagulation has to be continued by alternative drugs. The
heparinoid danaparoid-sodium and the thrombin inhibitor recombinant hirudin have
been used successfully world-wide for treatment in many patients with HIT Type
II including cardiopulmonary bypass surgery or renal replacement procedures.
Furthermore, other therapeutical alternatives (e.g. immunoglobulins,
prostaglandines) exist. Randomised controlled studies have to evaluate which
drug has to be preferred in the future including risk/benefit ratio. The need of
supplementary surgical procedures (e.g. embolectomy) depends on the individual
clinical status. The patients have to be informed in detail about their
underlying disease and further deleterious consequences of re-exposition with
heparin. HIT should be recorded in an emergency certificate and the national
Committee on Drugs should be informed about this severe side effect of heparin
therapy.
Publication Types:
Review
Review, Tutorial
PMID: 10631436 [PubMed - indexed for MEDLINE]
83: J Extra Corpor Technol 1998 Dec;30(4):193-6
Perfusing the Jehovah's Witness patient with heparin-induced thrombocytopenia.
Brown DM.
Heart Institute of Spokane, Washington 99203, USA.
Heparin-induced thrombocytopenia (HIT) is an uncommon, yet dangerous side-effect
of heparin therapy. The problems associated with the HIT patient while
undergoing cardiopulmonary bypass increase dramatically when the patient is also
of Jehovah's Witness faith. This case report depicts the techniques utilized and
the decisions made over the course of a simple surgical procedure for an
extremely high-risk patient.
PMID: 10537581 [PubMed - indexed for MEDLINE]
84: Ann Thorac Surg 1999 Sep;68(3):1076-8
Pediatric heparin-induced thrombocytopenia: management with Danaparoid
(orgaran).
Saxon BR, Black MD, Edgell D, Noel D, Leaker MT.
Division of Haematology/Oncology, The Hospital for Sick Children, Toronto,
Ontario, Canada.
Heparin-induced thrombocytopenia is a rare and serious complication of
anticoagulation therapy. There remains a paucity of information pertaining to
alternative anticoagulation strategies for use during cardiopulmonary bypass
concomitant with heparin-induced thrombocytopenia, especially in children. We
report the successful treatment of heparin-induced thrombocytopenia and
subsequent hemorrhagic complications postoperatively in a 2-year-old child with
Danaparoid (orgaran). Emergent conduit revision with cardiopulmonary bypass was
required for a thrombosed systemic-venous to pulmonary-arterial connection
(completion modified Fontan procedure). Required doses of Danaparoid were
consistently twofold that previously reported for adults.
PMID: 10510017 [PubMed - indexed for MEDLINE]
85: Curr Opin Hematol 1999 Sep;6(5):342-8
Laboratory markers of platelet activation and their clinical significance.
Michelson AD, Furman MI.
Center for Platelet Function Studies, Department of Pediatrics, University of
Massachusetts Medical School, Worcester 01655, USA. michelson@platelets.org
Whole blood flow cytometry is a powerful new laboratory technique for assessment
of platelet activation and function. Flow cytometry can be used to measure
platelet hyperreactivity, circulating activated platelets, leukocyte-platelet
aggregates, and procoagulant platelet-derived microparticles in a number of
clinical settings, including acute coronary syndromes, angioplasty,
cardiopulmonary bypass, acute cerebrovascular ischemia, peripheral vascular
disease, diabetes mellitus, preeclampsia, and Alzheimer's disease. Clinical
applications of whole blood flow cytometric assays of platelet function in these
diseases may include identification of patients who would benefit from
additional antiplatelet therapy and prediction of ischemic events. Circulating
monocyte-platelet aggregates appear to be a more sensitive marker of in vivo
platelet activation than circulating P-selectin-positive platelets. Flow
cytometry can also be used in the following clinical settings: monitoring of
glycoprotein IIb-IIIa antagonist therapy, diagnosis of inherited deficiencies of
platelet surface glycoproteins, diagnosis of storage pool disease, diagnosis of
heparin-induced thrombocytopenia, and measurement of the rate of thrombopoiesis.
Publication Types:
Review
Review, Tutorial
PMID: 10468151 [PubMed - indexed for MEDLINE]
86: Semin Thromb Hemost 1999;25 Suppl 1:9-15
Heparin-induced thrombocytopenia in France, 1980-1998.
Nguyen P, de Maistre E, Cornillet-Lefebvre P, Regnault V, Lecompte T.
Laboratoire d'Hematologie, CHU Robert-Debre, Reims, France.
Due to the extensive use of unfractionated heparins in France, there is
considerable experience with heparin-induced thrombocytopenia (HIT). It is
recommended that platelet counts be performed twice a week for three weeks when
patients are treated with any form of heparin. A drop in platelet counts can,
however, occur not only in HIT patients but also for other unrelated reasons.
For diagnosing HIT, all laboratories in France use platelet aggregometry inspite
of poor sensitivity. Both false positive and false negative results are
obtained. The serotonin release test is not used in France. The ELISA test for
HIT does not always correlate with the platelet aggregation test and many
patients with a positive ELISA test do not necessarily have other evidence for
HIT. This is especially true in patients following cardiopulmonary bypass
surgery. None of the available laboratory tests reliably identify patients with
HIT. Patients with HIT should not be managed with low-molecular-weight heparins,
but danaparoid, argatroban and ancrod are viable options. Also, recombinant
hirudin has been employed. All have advantages and disadvantages. At present,
the diagnosis and management of patients with HIT remains difficult and properly
designed clinical studies are needed to obtain answers to several open
questions.
PMID: 10357146 [PubMed - indexed for MEDLINE]
87: Circulation 1999 May 18;99(19):2530-6
Antibodies to platelet factor 4-heparin after cardiopulmonary bypass in patients
anticoagulated with unfractionated heparin or a low-molecular-weight heparin :
clinical implications for heparin-induced thrombocytopenia.
Pouplard C, May MA, Iochmann S, Amiral J, Vissac AM, Marchand M, Gruel Y.
Departments of Hematology, Anesthesiology and Cardiac Surgery, Gennevilliers,
France.
BACKGROUND: Cardiopulmonary bypass (CPB) induces platelet activation with
release of platelet factor 4 (PF4), and patients are exposed to high doses of
heparin (H). We investigated whether this contributes to the development of
antibodies to H-PF4 and heparin-induced thrombocytopenia (HIT). METHODS AND
RESULTS: CPB was performed with unfractionated heparin (UFH) in 328 patients.
After surgery, patients received UFH (calcium heparin, 200 IU. kg-1. d-1) (group
1, n=157) or low-molecular-weight heparin (LMWH, Dalteparin, 5000 IU once daily)
(group 2, n=171). Eight days after surgery, antibodies to H-PF4 were present in
83 patients (25.3%), 46 in group 1 and 37 in group 2 (P=0.12). Most patients
(61%) had IgG1 to H-PF4, but only 8 samples with antibodies induced platelet
activation with positive results on serotonin release assay. HIT occurred in 6
patients in group 1, but no thrombocytopenia was observed in subjects receiving
LMWH, although 2 had high levels of antibodies with positive serotonin release
assay results. When antibodies to H-PF4 were present, mean platelet counts were
lower only in patients with FcgammaRIIA R/R131 platelets. CONCLUSIONS: These
results provide evidence that the development of antibodies to H-PF4 after CPB
performed with UFH is not influenced by the postoperative heparin treatment. The
antibodies associated with high risk of HIT are mainly IgG1, which is present at
high titers in the plasma of patients continuously treated with UFH.
PMID: 10330384 [PubMed - indexed for MEDLINE]
88: Thorac Cardiovasc Surg 1999 Feb;47(1):9-13
Surgical therapy of fulminant pulmonary embolism: early and late results.
Doerge H, Schoendube FA, Voss M, Seipelt R, Messmer BJ.
Department of Thoracic and Cardiovascular Surgery, RWTH University Hospital,
Aachen, Germany.
BACKGROUND: Pulmonary embolectomy remains the only option for patients with
fulminant pulmonary embolism and failure or contraindication of thrombolysis
even today. Increasing prevalence of heparin-induced thrombocytopenia type II
(HIT) adds a new significant problem, which was investigated in a retrospective
study. METHODS: Between 1/1979 and 1/1998 41 patients (21 male; age: 51.1 +/-
14.8 years) with fulminant pulmonary embolism underwent pulmonary embolectomy
under cardiopulmonary bypass: group I (1979-89): 31 patients; group II
(1990-98): 10 patients. Group II included only patients who did not meet the
criteria for acute thrombolysis, in 4 patients a HIT was preoperatively assured.
All patients were in strongly compromised hemodynamic condition (33/41 high-dose
catecholamines, 24/41 mechanical ventilation, 14/41 preoperative cardiopulmonary
resuscitation). RESULTS: Perioperative mortality was 29% (group I: 9/31; group
II: 3/10; n.s.) Preoperative resuscitation was the only predictive factor (with
resuscitation: 9/14; without resuscitation: 3/27; p < 0.001). Severe but not
fatal complications occurred in 11 patients: they fully recovered following
treatment. Follow-up was completed to 93% (281 patient-years; mean: 10.6 years)
and discovered 5 late deaths (late mortality: 1.7%/patient-year; 1 patient:
bleeding due to anticoagulation; 4 patients: not related to operation). 26/28
(93%) patients were in NYHA functional class I or II. No recurrent pulmonary
embolism or late clinical symptoms related to embolectomy were observed. There
was no difference between group I and group II (including the 4 patients with
HIT) regarding perioperative mortality, complication, and late results.
ConCLUSIONS: Pulmonary embolectomy on cardiopulmonary bypass remains an adequate
therapy in patients with failure of or contraindication to thrombolysis, and HIT
is not a contraindication.
PMID: 10218613 [PubMed - indexed for MEDLINE]
89: Wien Klin Wochenschr 1999 Feb 26;111(4):129-40
Anticoagulation with prostaglandins during extracorporeal circulation.
Kozek-Langenecker SA.
Department of Anaesthesiology and General Intensive Care, University of Vienna,
Austria.
This paper reviews pathophysiological processes occurring after contact of blood
with artificial surfaces and the predominant role of platelets in the genesis of
extracorporeal thrombosis. Bleeding complications are common during conventional
heparin anticoagulation, and both clinical and experimental evidence suggests
that the efficacy of heparin as an anticoagulant is compromised by its relative
ineffectiveness towards platelets. Consequently, drugs that inhibit interaction
between platelets and artificial membranes have been introduced as an
alternative anticoagulant strategy. This paper reviews studies on the use of
short-acting antiplatelet prostaglandins such as prostacyclin and prostaglandin
E1 alone or in combination with heparin during various forms of extracorporeal
circulation such as cardiopulmonary bypass, haemodialysis, continuous
haemofiltration, membrane oxygenation, ventricular assist devices, and
haemoperfusion. Temporary paralysis of platelet function with antiplatelet
prostaglandins has been effective in controlling platelet-surface interaction
and reducing bleeding complications and morbidity during and after
extracorporeal circulation. By inhibiting the formation of fibrin, leukocyte and
platelet-based microaggregates and cytoprotective actions, prostaglandins have
been shown to prevent renal, neurologic, and pulmonary dysfunction after
extracorporeal circulation. Prostaglandins were most effective in increasing the
biocompatibility of extracorporeal systems when they were administered as a
supplement to but not as a substitute for heparin. The use of prostaglandins
alone should be reserved for patients who are resistant to heparin or
heparin-induced thrombocytopenia.
Publication Types:
Review
Review, Tutorial
PMID: 10192145 [PubMed - indexed for MEDLINE]
90: Curr Opin Cardiol 1992 Apr;7(2):267-75
Cardiopulmonary bypass surgery.
Utley JR.
Spartanburg Regional Medical Center, Spartanburg, South Carolina.
New information on cardiopulmonary bypass continues to be produced by
investigators from many disciplines. Investigations are related to problems and
complications resulting from use of the heart-lung machine. The relationship of
perfusion and pressure during bypass in brain, kidney, and other organs is the
subject of several reports. The studies confirm that low flow and pressure are
safe with hemodilution and hypothermia. Investigations related to the pH stat
and alpha stat blood gas schemes are sometimes inconclusive, but significant
observations favor the use of the alpha stat blood gas scheme. The
complications of choreoathetosis in pediatric patients appears to be related to
low levels of hypothermia. Studies continue to show the many adverse effects of
cardiopulmonary bypass on platelets, leukocytes, and the complement system. The
minimum acceptable activated clotting time during cardiopulmonary bypass may be
less than 400 seconds. Other authors address the complications of protamine
infusion and heparin-induced thrombocytopenia.
Publication Types:
Review
Review, Tutorial
PMID: 10171189 [PubMed - indexed for MEDLINE]
91: Circulation 1999 Jan 5-12;99(1):73-80
Recombinant hirudin (lepirudin) provides safe and effective anticoagulation in
patients with heparin-induced thrombocytopenia: a prospective study.
Greinacher A, Volpel H, Janssens U, Hach-Wunderle V, Kemkes-Matthes B, Eichler
P, Mueller-Velten HG, Potzsch B.
Institute for Immunology and Transfusion Medicine,
Ernst-Moritz-Arndt-University, Greifswald, Germany.
greinach@rz.uni-greifswald.de
BACKGROUND: The immunological type of heparin-induced thrombocytopenia (HIT) is
the most frequent drug-induced thrombocytopenia. This study evaluated the
efficacy of recombinant hirudin (r-hirudin or lepirudin), a potent thrombin
inhibitor, for anticoagulation in patients with confirmed HIT. METHODS AND
RESULTS: Eighty-two patients in this prospective, multicenter study received 1
of 4 intravenous r-hirudin regimens: A1, HIT patients with thrombosis (n=51),
0.4-mg/kg bolus and then 0.15 mg. kg-1. h-1; A2, HIT patients with thrombosis
receiving thrombolysis (n=5), 0. 2-mg/kg bolus and then 0.1 mg. kg-1. h-1; B,
HIT patients without thrombosis (n=18), 0.1 mg. kg-1. h-1; and C, during
cardiopulmonary bypass surgery (n=8), 0.25-mg/kg bolus and then 5-mg boluses as
needed. Response criteria were increase in platelet count by >/=30% to >10(9)/L
and activated partial thromboplastin time (aPTT) values 1.5 to 3.0 times
baseline values achieved with a maximum of 2 dose increases. No placebo control
was used for ethical reasons. Outcomes of a subset of r-hirudin-treated patients
who met predefined inclusion criteria (n=71) were compared with those of a
historical control group (n=120) for combined and individual incidences of
death, amputations, new thromboembolic complications, and incidences of
bleeding. Platelet counts increased rapidly in 88.7% of r-hirudin-treated
patients with acute HIT. In regimens A1 and A2, the 25% and 75% quartiles of the
aPTT were within the target range at all but 1 time point. The incidence of the
combined end point (death, amputation, new thromboembolic complications) was
significantly reduced in r-hirudin patients compared with historical control
patients (P=0.014). During first selected treatment, the adjusted hazard ratio
for r-hirudin patients versus historical control was 0.279 (95% CI, 0.112 to
0.699; P=0.003). Bleeding rates were similar in both groups. CONCLUSIONS:
r-Hirudin treatment is associated with a rapid and sustained recovery of
platelet counts, sufficient aPTT prolongations, and true clinical benefits for
patients with HIT.
Publication Types:
Clinical Trial
Controlled Clinical Trial
Multicenter Study
PMID: 9884382 [PubMed - indexed for MEDLINE]
92: Anesthesiology 1998 Sep;89(3):777-80
Emergent cardiopulmonary bypass in five patients with heparin-induced
thrombocytopenia type II employing recombinant hirudin.
Koster A, Kuppe H, Hetzer R, Sodian R, Crystal GJ, Mertzlufft F.
Department of Anesthesiology, German Heart Center, Berlin.
PMID: 9743416 [PubMed - indexed for MEDLINE]
93: Ann Thorac Surg 1998 Aug;66(2):567-9
Cardiopulmonary bypass with danaparoid sodium and ancrod in heparin-induced
thrombocytopenia.
Kanagasabay RR, Unsworth-White MJ, Robinson G, Bevan D, Farnsworth G, Haxby EJ,
Smith EE.
Department of Cardiothoracic Surgery, St George's Hospital, London, England.
rkanaga@sghms.ac.uk
Heparin is the standard anticoagulant for patients undergoing cardiopulmonary
bypass. There are some patients for whom heparin is unsuitable and ancrod (a
defibrinogenating enzyme) has been used as an alternative. We present a patient
with heparin-induced thrombocytopenia in whom treatment ancrod was ineffective.
The addition of danaparoid sodium (a heparinoid) allowed safe cardiopulmonary
bypass. We discuss the reasons for this and suggest that the combination of
ancrod and danaparoid sodium is a logical one in such cases.
PMID: 9725413 [PubMed - indexed for MEDLINE]
94: J Heart Lung Transplant 1998 Jul;17(7):729-31
Comment in:
J Heart Lung Transplant. 2000 May;19(5):510-2.
Heart transplantation in patients with heparin-induced thrombocytopenia on the
Novacor left ventricular assist system.
Brozena SC, Twomey C, Siegel J, Peterson P, Horrow JC, Samuels L, Morris R.
Department of Medicine, MCP, Hahnemann School of Medicine of the Allegheny
University of the Health Sciences, Philadelphia, PA, USA.
We report on two patients with development of heparin-induced thrombocytopenia
with thrombosis while on the Novacor left ventricular assist system. Heart
transplantation was successfully performed in both patients with heparin used
for cardiopulmonary bypass after careful monitoring of heparin-associated
antibodies. The approach to the patients' management and potential alternatives
for anticoagulation are discussed.
PMID: 9703240 [PubMed - indexed for MEDLINE]
95: Br J Haematol 1998 Jun;101(4):653-5
High incidence of anti-heparin/platelet factor 4 antibodies after
cardiopulmonary bypass surgery.
Trossaert M, Gaillard A, Commin PL, Amiral J, Vissac AM, Fressinaud E.
Laboratoire d'Hematologie, C.H.U., Nantes, France.
Fifty-one patients undergoing cardiopulmonary bypass (CPB) were studied on day 0
and day 8 for heparin-induced thrombocytopenia (HIT). The platelet aggregation
test (PAT) and tests for anti-heparin-platelet factor 4 (anti-H.PF4), anti-IL8
and anti-neutrophil activating peptide 2 (anti-NAP2) antibodies (Ab) were
performed by ELISA. On day 8, 27% of patients were positive for anti-H.PF4Ab.
None of these results were found to influence thrombotic complications or
platelet counts after CPB. Our results suggest that IgG to H.PF4 may be
considered a risk factor, but that additional factors must be required for HIT
to develop. We conclude that assays based on platelet activation would be more
appropriate for the diagnosis of HIT after CPB.
PMID: 9674736 [PubMed - indexed for MEDLINE]
96: J Thorac Cardiovasc Surg 1998 May;115(5):1179-88
Heparinless cardiopulmonary bypass with active-site blocked factor IXa: a
preliminary study on the dog.
Spanier TB, Oz MC, Minanov OP, Simantov R, Kisiel W, Stern DM, Rose EA, Schmidt
AM.
Department of Surgery, Columbia University College of Physicians and Surgeons,
New York, NY 10032, USA.
OBJECTIVE: Cardiopulmonary bypass is a potent stimulus for activation of
procoagulant pathways. Heparin, the traditional antithrombotic agent, however,
is often associated with increased perioperative blood loss because of its
multiple sites of action in the coagulation cascade and its antiplatelet and
profibrinolytic effects. Furthermore, heparin-mediated immunologic reactions
(that is, heparin-induced thrombocytopenia) may contraindicate its use.
Cardiopulmonary bypass with a selective factor IXa inhibitor was tested to see
whether it could effectively limit bypass circuit/intravascular space thrombosis
while decreasing extravascular bleeding, thereby providing an alternative
anticoagulant strategy when heparin may not be safely administered. METHODS:
Active site-blocked factor IXa, a competitive inhibitor of the assembly of
factor IXa into the factor X activation complex, was prepared by modification of
the enzyme's active site by the use of dansyl glutamic
acid-glycine-arginine-chlormethylketone. Twenty mongrel dogs (five were given
standard heparin/protamine; 15 were given activated site-blocked factor IXa
doses ranging from 300 to 600 microg/kg) underwent 1 hour of hypothermic
cardiopulmonary bypass, and blood loss was monitored for 3 hours after the
procedure. RESULTS: Use of activated site-blocked factor IXa as an anticoagulant
in cardiopulmonary bypass limited fibrin deposition within the extracorporeal
circuit as assessed by scanning electron microscopy, comparable with the
antithrombotic effect seen with heparin. In contrast to heparin, effective
antithrombotic doses of activated site-blocked factor IXa significantly
diminished blood loss in the thoracic cavity and in an abdominal incisional
bleeding model. CONCLUSION: These initial studies on the dog suggest that
administration of activated site-blocked factor IXa may be an effective
alternative anticoagulant strategy in cardiopulmonary bypass when heparin is
contraindicated, affording inhibition of intravascular/extracorporeal circuit
thrombosis with enhanced hemostasis in the surgical wound.
PMID: 9605089 [PubMed - indexed for MEDLINE]
97: J Vasc Surg 1998 Mar;27(3):568-75
Intraoperative monitoring of danaparoid sodium anticoagulation during
cardiovascular operations.
Gitlin SD, Deeb GM, Yann C, Schmaier AH.
Department of Internal Medicine, University of Michigan, Ann Arbor 48109-0640,
USA.
PURPOSE: Patients with cardiovascular disorders frequently need anticoagulation
for diagnostic studies, surgical procedures, and therapy. Heparin-induced
thrombocytopenia is a relatively common complication of heparin therapy that can
result in thrombosis and subsequent limb loss or death, necessitating use of
alternative anticoagulants. METHODS: Two patients who needed cardiac surgery had
thrombocytopenia induced by exposure to heparin and heparin-coated tubing.
Several assays were examined for their ability to monitor intraoperative
anticoagulation of a factor Xa inhibitor, danaparoid sodium. RESULTS: In vitro,
celite and kaolin activated dotting times and activated partial thromboplastin
time were prolonged linearly in the presence of increasing concentrations of
danaparoid sodium. Aprotinin did not alter the linearity of the response but did
alter its slope. In vivo, activated clotting times and activated partial
thromboplastin time were insensitive to clinically significant changes in
danaparoid sodium plasma levels during cardiopulmonary bypass. Correction in
activated partial thromboplastin time lagged 2 hours behind clinically important
changes in anti-factor Xa levels. Only anti-factor Xa levels were adequate to
monitor intraoperative danaparoid sodium levels. CONCLUSION: Anticoagulation for
cardiopulmonary bypass can be successfully performed with danaparoid sodium and
intraoperative anti-factor Xa monitoring.
PMID: 9546248 [PubMed - indexed for MEDLINE]
98: Thorac Cardiovasc Surg 1997 Dec;45(6):318-20
Heparin-induced thrombocytopenia type II: perioperative management using
danaparoid in a coronary artery bypass patient with renal failure.
Westphal K, Martens S, Strouhal U, Matheis G, Lindhoff-Last E, Wimmer-Greinecker
G, Lischke V.
Department of Anaesthesiology and Resuscitation, J. W. Goethe University,
Frankfurt, Germany.
An 84-year-old patient with heparin-induced thrombocytopenia (HIT), global
cardiac decompensation, and acute renal failure underwent a cardiosurgical
intervention using an extracorporeal circuit. For systemic anticoagulation
danaparoid (Orgaran) was applied as a heparin substitute preoperatively and
maintained for systemic anticoagulation during ECC despite it being eliminated
by the kidney. The postoperative recovery was prolonged due to bleeding
complications. During cardiopulmonary bypass (216 min) the target level of
anti-factor Xa was 1.5 UI/ml. This required continuous infusion and an
occasional bolus of danaparoid. Coagulation in the extracorporeal circuit was
observed twice at plasma levels below 1.4 IU/ml. There were no thromboembolic or
neurologic events. We did not retransfuse blood from the extracorporeal circuit
or the cardiotomy reservoir after bypass, but because elimination of danaparoid
was impaired in this patient and there is no neutraliser available antifactor Xa
postoperatively exceeded 0.6 IU/ml for 30 hours. Diffuse bleeding with tamponade
resulted. Weaning the patient from the respirator was achieved 12 hours after
the last re-exploration. From the 4th postoperative day 750 IU of danaparoid
were administered twice daily subcutaneously for thrombosis prevention. On the
6th postoperative day discharge from the ICU was possible. We conclude that the
application of danaparoid for cardiopulmonary bypass in patients suffering from
acute renal failure may be complicated by hemorrhage.
PMID: 9477469 [PubMed - indexed for MEDLINE]
99: J Cardiothorac Vasc Anesth 1997 Dec;11(7):875-7
Coagulation complicating cardiopulmonary bypass in a patient with
heparin-induced thrombocytopenia receiving the heparinoid, danaparoid sodium.
Grocott HP, Root J, Berkowitz SD, deBruijn N, Landolfo K.
Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710,
USA.
PMID: 9412888 [PubMed - indexed for MEDLINE]
100: ASAIO J 1997 Sep-Oct;43(5):M430-3
Heparin induced thrombocytopenia. Experiences in 12 heart surgery patients.
Sodian R, Loebe M, Gorman KF, Riess H, Hetzer R.
Department of Cardiovascular and Thoracic Surgery, Deutsches Herzzentrum Berlin,
Germany.
A heparin induced thrombocytopenia Type II (HIT) is a dangerous complication of
heparin therapy. Bleeding, but above all serious thromboembolic complications,
which may result in crippling disabilities or even death, can develop. Twelve
heart surgery patients who were diagnosed with a HIT Type II are reported. Seven
of the patients were diagnosed post operatively, the other five pre-operatively.
Two of these patients underwent heart surgery with r-Hirudin (Behringwerke AG,
Marburg, Germany) on cardiopulmonary bypass and two on Orgaran (AKZO Organon,
the Netherlands). Of the seven post operative HIT patients, four had had a
bypass operation and each had received a mitral or aortic valve replacement.
Another patient had received an artificial biventricular support system (Berlin
Heart) and was diagnosed with HIT Type II post operatively. Because of his
special condition, this patient underwent anticoagulation with Orgaran and heart
transplantation with Orgaran on a heart lung machine. Upon suspicion of HIT Type
II, heparin therapy was immediately halted and an alternative treatment of
Orgaran or r-Hirudin was begun. One patient encountered bleeding of a gastric
ulcer on Orgaran therapy. Heart surgery patients, especially patients with an
artificial support system, are potentially lethally threatened by serious
thromboembolic complications accompanying HIT Type II. Therefore, these patients
must be diagnosed as early as possible. Orgaran along with r-Hirudin are
effective heparin substitutes in patients with HIT Type II. These medications
can be widely administered to heart surgery patients pre-, intra-, and post
operatively without complication.
PMID: 9360077 [PubMed - indexed for MEDLINE]
101: Br J Haematol 1997 Sep;98(3):657-9
Danaparoid for cardiopulmonary bypass in patients with previous heparin-induced
thrombocytopenia.
Gillis S, Merin G, Zahger D, Deeb M, Drenger B, Hyam E, Eldor A.
Department of Haematology, Hadassah University Medical Centre, Ein Karem,
Jerusalem, Israel.
Anticoagulation for cardiopulmonary bypass in patients with heparin-induced
thrombocytopenia requires the use of other anticoagulants. We report a case in
whom this was achieved using the heparinoid danaparoid (Orgaran). Based on our
experience and a review of the literature, we provide guidelines for managing
these rare patients. A danaparoid dose substantially lower than that recommended
by the manufacturer may minimize bleeding complications.
PMID: 9332322 [PubMed - indexed for MEDLINE]
102: J Cardiothorac Vasc Anesth 1997 Apr;11(2):262-3
Comment on:
J Cardiothorac Vasc Anesth. 1996 Jun;10(4):521-30.
Orgaran (Org 10172) for cardiopulmonary bypass in heparin-induced
thrombocytopenia: role of adjunctive plasmapheresis.
Schmahl KS, Ganjoo AK, Harloff MG.
Publication Types:
Comment
Letter
PMID: 9106004 [PubMed - indexed for MEDLINE]
103: Semin Thromb Hemost 1997;23(2):225-33
Anticoagulants and extracorporeal circuits.
Beijering RJ, ten Cate H, Nurmohamed MT, ten Cate JW.
Center for Hemostasis, Thrombosis, Atherosclerosis, and Inflammation Research,
AMC, University of Amsterdam, The Netherlands.
Anticoagulants are pivotal to achieve circulation in extracorporeal circuits. In
this review we discuss several anticoagulants in clinical use or in the
preclinical phase. In hemodialysis the low-molecular-weight heparins (LMWHs)
appear to be as effective and safe as standard heparin (SH). The main advantages
of LMWHs in hemodialysis are the efficacy of a single loading dose, and the lack
of laboratory control requirements. Newer anticoagulants such as dermatan
sulfate and hirudin have been used in dose-finding studies in hemodialysis,
although long-term experience is lacking. LMW heparinoid may be used to replace
SH or LMWH in the case of heparin-induced thrombocytopenia. In cardiopulmonary
bypass surgery (CPB) heparin-coated extracorporeal circuits are now being
commonly applied. Their main advantage is the requirement of lower systemic
dosages of heparin. In CPB the place of LMWH or other anticoagulants needs to be
investigated.
Publication Types:
Review
Review, Tutorial
PMID: 9200350 [PubMed - indexed for MEDLINE]
104: J Cardiothorac Vasc Anesth 1996 Dec;10(7):918-21
Hematologic changes in a patient with heparin-induced thrombocytopenia who
underwent cardiopulmonary bypass after ancrod defibrinogenation.
Spiess BD, Gernsheimer T, Vocelka C, Chandler WL, Benak A, Joy JV, Wright I,
Hofer BO.
Department of Anesthesia, University of Washington, Seattle 98195, USA.
PMID: 8969402 [PubMed - indexed for MEDLINE]
105: J Thorac Cardiovasc Surg 1996 Nov;112(5):1390-2
Comment in:
J Thorac Cardiovasc Surg. 1997 Sep;114(3):517-8.
Cardiopulmonary bypass for heparin-induced thrombocytopenia: management with a
heparin-bonded circuit and enoxaparin.
Ganjoo AK, Harloff MG, Johnson WD.
St. Mary's Hospital, Milwaukee, Wis, USA.
PMID: 8911341 [PubMed - indexed for MEDLINE]
106: J Cardiothorac Vasc Anesth 1996 Oct;10(6):809-15
Case 5--1996. Thrombosis after the use of a heparin-coated cardiopulmonary
bypass circuit in a patient with heparin-induced thrombocytopenia.
Van Dyck MJ, Lavenne-Pardonge E, Azerad MA, Matta AG, Moriau M, Comunale ME.
Department of Anesthesiology, University Hospital St-Luc, Catholic University of
Louvain Medical School (UCL), Brussels, Belgium.
Publication Types:
Clinical Conference
PMID: 8910165 [PubMed - indexed for MEDLINE]
107: J Cardiothorac Vasc Anesth 1996 Jun;10(4):521-30
Comment in:
J Cardiothorac Vasc Anesth. 1997 Apr;11(2):262-3.
J Cardiothorac Vasc Anesth. 1997 Jun;11(4):538-9.
Heparin-induced thrombocytopenia.
Shorten GD, Comunale ME.
Department of Anesthesia and Critical Care, Beth Israel Hospital, Boston, MA
02215, USA.
Publication Types:
Review
Review, Tutorial
PMID: 8776651 [PubMed - indexed for MEDLINE]
108: Ann Thorac Surg 1996 Mar;61(3):920-4
Cardiopulmonary bypass in patients with heparin-induced thrombocytopenia using
Org 10172.
Wilhelm MJ, Schmid C, Kececioglu D, Mollhoff T, Ostermann H, Scheld HH.
Department of Thoracic and Cardiovascular Surgery, University of Munster,
Germany.
BACKGROUND: In patients with heparin-induced thrombocytopenia undergoing cardiac
operations, anticoagulation with heparin should be avoided. The
low-molecular-weight glycosaminoglycan Orgaran has been used as an alternative,
but the overall experience is limited. METHODS: Two patients with
heparin-induced thrombocytopenia underwent cardiopulmonary bypass using Orgaran
for anticoagulation. A 30-year-old woman suffered from emboli to her brain
through a secondary atrial septal defect, a 14-year-old boy from ischemia of his
left leg due to recurrent embolism originating from the mitral valve. In both
cases, cardiopulmonary bypass was performed in a routine manner, except for
using low-dose Orgaran instead of heparin. Anticoagulation was monitored during
cardiopulmonary bypass by measuring Orgaran plasma levels and activated clotting
time. RESULTS: No thromboembolic or bleeding complications occurred during and
after atrial septal defect repair and mitral valve replacement, respectively. In
the former case, thrombotic material from the inferior vena cava was removed
during hypothermic circulatory arrest within the same procedure. Activated
clotting time did not correlate with plasma levels of Orgaran. CONCLUSIONS:
Orgaran might be a useful alternative for anticoagulation during extracorporeal
circulation. Adequate dosages and measurement of plasma levels are recommended
for its use in cardiopulmonary bypass.
PMID: 8619718 [PubMed - indexed for MEDLINE]
109: Thromb Haemost 1995 May;73(5):890
Which patients undergoing cardiopulmonary bypass should be assessed for
development of heparin-induced thrombocytopenia?
Cummins D, Halil O, Amin S.
Publication Types:
Letter
PMID: 7482421 [PubMed - indexed for MEDLINE]
110: Ann Thorac Surg 1995 Feb;59(2):508-9
Comment in:
Ann Thorac Surg. 1995 Oct;60(4):1159-60.
Heparin-induced thrombocytopenia and heart operation: management with
tedelparin.
Altes A, Martino R, Gari M, Camara ML, Garin R, Casas JI, Fontcuberta J.
Unitat d'Hemostasia i Trombosi, Servei de Cirurgia Cardiaca, Barcelona, Spain.
Anticoagulation for cardiopulmonary bypass in the infrequent clinical setting of
thrombocytopenia associated with the use of unfractionated heparin is a very
serious problem. We describe a case in which a low-molecular-weight heparin
(tedelparin) was selected for this purpose based on a platelet aggregation test,
permitting adequate anticoagulation during cardiopulmonary bypass for valve
replacement. This case report might help establish an adequate anticoagulation
protocol when faced with a patient suffering from this condition.
PMID: 7847976 [PubMed - indexed for MEDLINE]
111: Ann Thorac Surg 1994 Dec;58(6):1764-6
Heparin-induced thrombocytopenia and thrombosis: presentation after
cardiopulmonary bypass.
Munver R, Schulman IC, Wolf DJ, Rosengart TK.
New York Hospital-Cornell University Medical College, New York 10021.
Heparin-induced thrombocytopenia and thrombosis syndrome was diagnosed in a
63-year-old woman 11 days after coronary artery bypass grafting. Her only
presenting complaints were incisional leg pain and vague chest discomfort. The
syndrome was suspected when her platelet count was found to be 37,000/microL. A
subsequent ventilation-perfusion lung scan showed findings highly probable for
pulmonary embolism. An inferior venacavogram obtained before a pulmonary
angiogram revealed a large retrohepatic thrombus at the right atrial junction.
The patient was successfully treated with the defibrinogenating agent ancrod
(Arvin). A diagnosis of heparin-induced thrombocytopenia and thrombosis syndrome
should be considered and heparin therapy should be avoided in patients with low
platelet counts who have been previously treated with heparin.
PMID: 7979757 [PubMed - indexed for MEDLINE]
112: J Cardiothorac Vasc Anesth 1994 Oct;8(5):556-8
Management of cardiopulmonary bypass in a patient with heparin-induced
thrombocytopenia using prostaglandin E1 and aspirin.
Shorten G, Comunale ME, Johnson RG.
Department of Anesthesia and Critical Care, Harvard Medical School Boston, MA
02215.
PMID: 7803746 [PubMed - indexed for MEDLINE]
113: Ann Thorac Surg 1994 Aug;58(2):344-50
Pilot study of the efficacy of a thrombin inhibitor for use during
cardiopulmonary bypass.
DeAnda A Jr, Coutre SE, Moon MR, Vial CM, Griffin LC, Law VS, Komeda M, Leung
LL, Miller DC.
Department of Cardiovascular and Thoracic Surgery, Standford University School
of Medicine, CA 94305-5247.
Heparin is normally used for anticoagulation during cardiopulmonary bypass
(CPB), but its use is contraindicated in patients with a history of
heparin-induced thrombocytopenia, heparin-provoked thrombosis, or both. Heparin
therapy can also be ineffective due to heparin resistance. A short-acting,
oligonucleotide-based thrombin inhibitor (thrombin aptamer) may potentially
serve as a substitute for heparin in these and other clinical situations. We
tested a novel thrombin aptamer in a canine CPB pilot study to determine its
anticoagulant efficacy, the resultant changes in coagulation variables, and the
aptamer's clearance mechanisms and pharmacokinetics. Seven dogs were studied
initially: Four received varied doses of the aptamer (to establish the
pharmacokinetic profile) and 3 received heparin. Subsequently, 4 other dogs
underwent CPB, receiving a constant infusion of the aptamer before CPB (to
characterize the baseline coagulation status), with partial CPB and
hemodilution, during 60 minutes of total CPB, and, finally, after a 2-hour
recovery period. At a 0.5 mg.kg-1.min-1 dose, the activated clotting time rose
with aptamer infusion from 106 +/- 12 seconds to 187 +/- 8 seconds (+/- 1
standard deviation) (p = 0.014), increased further with hemodilution (to 259 +/-
41 seconds; p = 0.017), and was even more prolonged during total CPB (> 1,500
seconds; p < 0.001). This later increase in the activated clotting time
paralleled a rise in the plasma concentration of the thrombin aptamer during
total CPB, as determined by high-performance liquid chromatography.(ABSTRACT
TRUNCATED AT 250 WORDS)
PMID: 8067830 [PubMed - indexed for MEDLINE]
114: Ann Thorac Surg 1994 Jun;57(6):1656-8
Heparinless cardiopulmonary bypass with ancrod.
O-Yurvati AH, Laub GW, Southgate TJ, McGrath LB.
Department of Surgery, Deborah Heart and Lung Center, Browns Mills, New Jersey
08015-1799.
A case is reported of a 22-year-old man with heparin-induced thrombocytopenia
and thrombosis syndrome and a right atrial foreign body (Greenfield filter).
Heparinless cardiopulmonary bypass for removal of the foreign body was conducted
by pretreatment with ancrod, a rapid-acting antifibrinolytic of pit viper venom
origin. Treatment protocol and a literature review are included in this article.
Publication Types:
Review
Review of Reported Cases
PMID: 8010823 [PubMed - indexed for MEDLINE]
115: Med Clin (Barc) 1994 Apr 30;102(16):637-8
[Low-molecular-weight heparin in a patient with heparin-induced thrombocytopenia
and a cardiopulmonary bypass]
[Article in Spanish]
Parama JA, Llorens R, Saenz de Buruaga J, Rocha E.
Publication Types:
Letter
PMID: 8208043 [PubMed - indexed for MEDLINE]
116: Pharmacol Rev 1994 Mar;46(1):89-109
Low molecular weight heparin: a critical analysis of clinical trials.
Green D, Hirsh J, Heit J, Prins M, Davidson B, Lensing AW.
Department of Medicine, Northwestern University Medical School, Chicago,
Illinois.
LMWHs are an important new class of antithrombotic agents. They differ from UFH
in having relatively more anti-Xa activity, greater bioavailability at low
doses, longer half-life, and more predictable anticoagulant response when
administered in fixed doses. These properties allow LMWHs to be administered QD
or at most BID and without laboratory monitoring. The incidence of
heparin-induced thrombocytopenia also appears to be lower with an LMWH than with
heparin. Given their favorable pharmacological profile, it was of interest to
critically appraise clinical trials of thromboprophylaxis and treatment with
these new agents. In orthopedic trials, it was noted that LMWH provided safe and
effective thromboprophylaxis for patients undergoing major orthopedic surgery of
the lower limb. In those having hip arthroplasty, LMWH was as effective as
low-intensity warfarin therapy, but its use was associated with more wound
hematomas. In those having total knee arthroplasty, LMWH was more effective than
warfarin and did not increase bleeding. However, the prevalence of DVTs
complicating this procedure as well as acute hip fracture remains unacceptably
high, and additional studies of LMWH in combination with other prophylactic
methods, such as external pneumatic compression, are needed. Only one adequately
designed trial found less bleeding resulted from LMWH prophylaxis administered
at an equivalent antithrombotic dose to UFH. In general medical patients, LMWH
appeared to be as effective as UFH and had the advantages of less frequent
injections and fewer injection site hematomas. In general surgical patients,
there was a lower risk of thromboembolism but a trend toward an increase in
bleeding events. Subjects with strokes and spinal cord injuries benefited from
fewer thrombotic events, and the latter had fewer bleeding complications. Other
potential indications for LMWH, such as cardiopulmonary bypass, hemodialysis,
and preservation of graft patency, are presently under study. Perhaps the most
impressive benefits of LMWH will be realized when it is used for the treatment
of venous thromboembolism. The meta-analysis presented in this review showed a
trend toward greater efficacy with LMWH and fewer major bleeding events in
comparison with adjusted-dose intravenous UFH. Also, during the months following
the thrombotic event, there was significantly less mortality in patients
receiving LMWH. A further advantage was the subcutaneous route of administration
and lack of requirement for laboratory monitoring. Additional treatment trials
are presently in progress and may establish LMWH as the treatment of choice for
patients with thromboembolic disorders.
Publication Types:
Review
Review, Academic
PMID: 8190751 [PubMed - indexed for MEDLINE]
117: Chest 1993 Nov;104(5):1436-40
Complications from heparin-induced thrombocytopenia in patients undergoing
cardiopulmonary bypass.
Singer RL, Mannion JD, Bauer TL, Armenti FR, Edie RN.
Department of Surgery, Jefferson Medical College, Philadelphia.
The purpose of this study was to evaluate retrospectively the incidence and
severity of heparin-induced thrombocytopenia (HIT)-related complications in
patients undergoing cardiopulmonary bypass. We reviewed the records of 1,500
consecutive patients who underwent cardiopulmonary bypass between August 1987
and December 1991 at Thomas Jefferson University Hospital. During this period of
time, there were 1,155 coronary artery bypass graft operations (77 percent); 225
valve replacements and repairs, or both (15 percent); 60 combination coronary
artery bypass graft or valve operations, or both (4 percent); and 60
miscellaneous procedures (4 percent). Although not all patients with
postoperative complications were tested for the HIT antibody, 11 patients (0.75
percent) were diagnosed with HIT. There were 17 complications in these 5 men and
6 women including 6 cases of ischemic limbs which required amputation, 4
strokes, 2 instances of saphenous vein graft occlusion with resulting myocardial
infarction, 2 cases of pulmonary emboli, 1 case of phlegmasia cerulea dolens,
and 2 deaths. The complications occurred an average of 3.6 days postoperatively,
with a range of occurrence of 1 to 11 days postoperatively. The mean nadir
platelet count at the time of recognition was 123,000/mm3 (range 32,000 to
193,000/mm3) with 9 of 11 patients (81.8 percent) having counts greater than
100,000/mm3. There was, however, a mean percent decrease in the platelet count
of 50 percent (range, 31 to 75 percent) from the time of first exposure to
heparin to the time of recognition of HIT. In our patients, HIT was not related
to the type, duration of treatment with or amount of heparin, or to pretreatment
with aspirin.
PMID: 8222802 [PubMed - indexed for MEDLINE]
118: Aust N Z J Med 1991 Feb;21(1):52-4
The use of a low molecular weight heparinoid (Org 10172) for extracorporeal
procedures in patients with heparin dependent thrombocytopenia and thrombosis.
Rowlings PA, Mansberg R, Rozenberg MC, Evans S, Murray B.
Department of Haematology, Prince Henry Hospital, Sydney, NSW.
We report two cases of heparin induced thrombocytopenia (HIT), in patients who
required anticoagulation for extracorporeal procedures (haemodialysis and
cardiopulmonary bypass) one associated with recurrent thrombosis of the
artificial circuits. Resolution of thrombocytopenia and successful
anticoagulation were achieved using a low molecular weight heparinoid (LMWH) Org
10172. Anticoagulation was monitored using estimations of plasma anti-factor Xa
activity. These cases demonstrate that LMWH provides safe and effective
anticoagulation in patients in whom unfractionated heparin has caused HIT.
PMID: 1709804 [PubMed - indexed for MEDLINE]
119: Angiology 1990 Dec;41(12):1075-81
Heparin-induced thrombocytopenia: a case report.
Van Damme H, Damas P, David JL, Limet R.
Department of Thoracic and Cardiovascular Surgery, University Hospital
Sart-Tilman, Liege, Belgium.
The authors report a case of heparin-induced thrombocytopenia, in whom massive
pulmonary embolism occurred in spite of heparin anticoagulation. Successful
pulmonary thrombectomy was carried out under cardiopulmonary bypass, with
limitation of platelet clumping during bypass by aggregation inhibitors. This
report is a comprehensive contribution to a better understanding of this rare
immunoallergic complication of heparin administration, with a high incidence of
serious thromboembolic events. The optimal management for cases of unavoidable
reexposure to heparin is discussed.
PMID: 2278404 [PubMed - indexed for MEDLINE]
120: Surgery 1990 Oct;108(4):686-92; discussion 692-3
Heparin-induced thrombocytopenia in patients who undergo open heart surgery.
Walls JT, Curtis JJ, Silver D, Boley TM.
Department of Surgery, University of Missouri, Columbia 65212.
To determine whether heparin-dependent antiplatelet antibodies (HAAb) have an
effect on morbidity and/or mortality rates, we reviewed the cases of 3438
patients who underwent open heart surgery from 1981 to 1989. Forty-six patients
(1.3%) had HAAb. The patients were divided into two groups: those patients who
were known to have HAAb before surgery (group I) and those patients who were
diagnosed with HAAb after surgery (group II). Group I patients (n = 5) were
pretreated with platelet-inhibiting drugs before reexposure to heparin during
cardiopulmonary bypass and were maintained with strict abstinence from heparin
afterward. Their lowest observed platelet counts ranged from 42,000/mm3 to
89,000/mm3 (median, 63,00/mm3). Thromboembolic complications did not occur, and
all patients survived. Group II patients (n = 41) who were diagnosed to have
HAAb after surgery had not been pretreated with platelet-inhibiting drugs before
surgery. Lowest platelet counts ranged from 11,000/mm3 to 128,000/mm3 (median,
42,000/mm3). Bleeding complications occurred in 21 patients (51%), and
thromboembolic complications occurred in 13 patients (32%). Hospital mortality
in group II patients was 37%. Late recognition of HAAb was associated with an
increase in morbidity and mortality rates. Thromboembolic complications of HAAb,
which had been diagnosed before surgery, were eliminated, and bleeding was
reduced by pretreatment with platelet-inhibiting drugs and strict abstinence
from heparin after surgery.
PMID: 2218881 [PubMed - indexed for MEDLINE]
121: J Card Surg 1990 Sep;5(3):177-89
Pathophysiology of cardiopulmonary bypass: current issues.
Utley JR.
Division of Cardiac Surgery, Spartanburg Regional Medical Center, South
Carolina.
Much of the research related to cardiopulmonary bypass in recent years has been
directed toward defining the changes in plasma and blood cells during bypass. In
this review, recent information is reexamined for six areas of current interest.
These areas are complement activation, immune response, anaphylactic reactions,
coagulation, and cerebral dysfunction. Complement may be activated by either the
classical or alternate pathway during cardiopulmonary bypass and protamine
administration. Membrane oxygenators appear to diminish the degree of complement
activation. Complement is a major factor in the whole body inflammatory
response; which often accompanies cardiopulmonary bypass. A product of
complement activation, C5a- desArg, causes activation and aggregation of
granulocytes. Other products of complement activation lead to lysis of blood
cells including granulocytes and red cells. Bubble oxygenators appear to have a
distinct disadvantage compared to membrane oxygenators regarding infection.
Airborne microorganisms are more likely to be entrained into circulating blood
with bubble oxygenators than with membrane oxygenators. Bubble oxygenators cause
a greater decrease in leukocyte number and function than membrane oxygenators.
Anaphylactic reactions have been associated with use of antibiotics, blood
products, protamine, and volume expanders during cardiopulmonary bypass.
Protamine reactions may be on an immunological basis or due to direct toxicity
of the drug. Free radicals including superoxide, hydrogen peroxide, and the
hydroxyl radical may be generated during cardiopulmonary bypass and reperfusion.
Free radical scavengers including; vitamin E, coenzyme Q, vitamin C, mannitol,
and glutathione have been studied. The avoidance of blood transfusion because of
risk of transmitted infection including AIDS has become a major goal in cardiac
surgery. Factors that correlate with increased transfusion requirement include
low hematocrit, female gender, increased age, small body size, low ejection
fraction, reoperation, and emergency operation. Heparin resistance due to
antithrombin III deficiency is being recognized more commonly. Antithrombin III
deficiency may be corrected with fresh frozen plasma. Patients with heparin
induced thrombocytopenia may be difficult to manage. Several management
protocols are suggested. The most straightforward appears to be the use of
aspirin preoperatively and platelet transfusions postoperatively. The incidence
of cerebral dysfunction after cardiopulmonary bypass depends on the sensitivity
of the test or indicator used. Perioperative stroke is associated with intrinsic
cerebrovascular disease and atherosclerosis of the ascending aorta. Retinal
angiograms during cardiopulmonary bypass show that microemboli are very common.
Cerebroplegia has been shown to extend the period of safe circulatory arrest in
animals. Much of the new knowledge concerning cardiopulmonary bypass is the
result of close collaboration between cardiac surgeons and nonsurgical
scientists.
Publication Types:
Review
Review, Tutorial
PMID: 2133841 [PubMed - indexed for MEDLINE]
122: Hematol Oncol Clin North Am 1990 Feb;4(1):145-55
Platelet function in cardiopulmonary bypass and artificial organs.
Addonizio VP.
Temple University Health Sciences Center, Department of Surgery, Philadelphia,
Pennsylvania.
Extensive contact between blood and synthetic surfaces is associated with both
quantitative and qualitative changes in platelet function. Cardiopulmonary
bypass is associated with a decline in the circulating platelet count, release
of platelet alpha granules and possibly platelet dense and lysosomal granule
release, and a prolongation of the bleeding time. It is assumed that these
platelet alterations contribute to postoperative blood loss and reoperation for
bleeding. Improvements in technology have reduced but not eliminated the adverse
platelet changes. Temporary inhibition of platelet function during surface
contact has achieved additional improvement in the setting of heparin-induced
thrombocytopenia but is not yet suitable for "routine" open heart surgery.
Long-term cardiopulmonary bypass or extracorporeal circulation membrane
oxygenation is receiving increased use during acute respiratory insufficiency.
Systemic anticoagulation is required. Bleeding and platelet consumption continue
as clinical problems and are treated by repeated platelet transfusion. Because
no air interface is present in this setting and the synthetic surface is
homogeneous this would appear to be the ideal area for application of platelet
functional inhibition and synthetic surface passivation to reduce platelet
consumption. Although still under review by the Food and Drug Administration,
pulsatile devices, including the total artificial heart, increasingly are being
used to provide temporary support for the failing heart. Furthermore, it is
likely that totally implantable devices will become available in the very near
future. Considering that thromboembolism is a major problem for recipients of
mechanical valves, it is likely that thromboembolism will persist as a limiting
factor in the further implementation of pulsatile devices. It is assumed that
imaginative antithrombotic therapy will be required and that platelet activation
will be fundamental to the thrombotic process. Platelet behavior in this
setting, however, remains incompletely characterized. The analytical methodology
that has been used to assess platelet behavior during cardiopulmonary bypass
should be applied to the pulsatile devices as well and results correlated with
clinical problems. This should permit standardization of antithrombotic therapy
and rational use of platelet functional inhibition.
Publication Types:
Review
Review, Academic
PMID: 2179210 [PubMed - indexed for MEDLINE]
123: Am Heart J 1990 Feb;119(2 Pt 1):368-74
Heparin-induced thrombocytopenia and arterial thrombosis: alternative therapies.
Cola C, Ansell J.
Department of Medicine, University of Massachusetts Medical School, Worcester
01655.
There are three distinct syndromes of heparin-induced thrombocytopenia: an acute
reversible from seen immediately after intravenous bolus injection, a
delayed-onset antibody-mediated form seen several days after the initiation of
therapy, and an intermediate type characterized by mild thrombocytopenia
developing just a few days after starting therapy. Delayed-onset heparin-induced
thrombocytopenia, clinically the most important form, results from the formation
of heparin-dependent antibodies that are directed against the platelet membrane.
In the presence of heparin, these antibodies may induce in vitro or in vivo
platelet aggregation. Consequently, the course may be complicated by arterial
thromboses. Treatment of this syndrome includes the prompt cessation of heparin.
Since continued or future anticoagulation is usually necessary, alternative
means of anticoagulation have been explored. Oral anticoagulation is often
started but requires several days to take effect. Other options include
low-molecular-weight heparins, antiplatelet agents, prostacyclin analogues, and
low-molecular-weight dextran. In vitro laboratory tests may be helpful in
guiding alternative therapy in some, but not all cases. Unfortunately, none of
these agents have proved to be uniformly effective and additional agents and
clinical investigation are needed before a definitive option becomes available.
Publication Types:
Review
Review, Tutorial
PMID: 1689094 [PubMed - indexed for MEDLINE]
124: Ann Thorac Surg 1989 Nov;48(5):712-3
Ancrod anticoagulation for cardiopulmonary bypass in heparin-induced
thrombocytopenia and thrombosis.
Teasdale SJ, Zulys VJ, Mycyk T, Baird RJ, Glynn MF.
Department of Anaesthesia, Toronto General Hospital, University of Toronto,
Ontario, Canada.
Heparin-induced thrombocytopenia and thrombosis was diagnosed in a 50-year-old
man undergoing a repeat heart operation after heparinization led to microemboli
and an eventual left transmetatarsal amputation. A third heart operation was
aborted when anticoagulation with low molecular weight heparin produced
intraoperative thrombi. The patient was referred to Toronto where ancrod (Arvin)
was used to lower plasma fibrinogen level, allowing successful repair of a
ventricular septal defect using cardiopulmonary bypass support. The patient made
an uneventful recovery.
PMID: 2818066 [PubMed - indexed for MEDLINE]
125: Surgery 1987 Nov;102(5):796-807
Prevention of heparin-induced thrombocytopenia during open heart surgery with
iloprost (ZK36374).
Addonizio VP Jr, Fisher CA, Kappa JR, Ellison N.
Department of Surgery, University of Pennsylvania School of Medicine,
Philadelphia 19104.
Recurrent thrombocytopenia, thrombosis, or sudden death may develop in patients
with heparin-induced thrombocytopenia who are reexposed to heparin. Three
patients came to us in whom a diagnosis of heparin-induced thrombocytopenia had
been made on the basis of clinical and serologic evidence; these patients
required reexposure to heparin because of urgent cardiac surgery. Therefore, we
evaluated the ability of iloprost (ZK36374), a new analogue of prostacyclin, to
prevent heparin-dependent activation of platelets and thereby permit obligatory
heparinization for safe extracorporeal circulation. Before operation, we
demonstrated that iloprost prevented both heparin-dependent platelet aggregation
and tritiated (3H)-serotonin release in vitro. Therefore a continuous infusion
of iloprost was begun 1 hour before heparinization and was continued throughout
cardiopulmonary bypass and for an additional 15 minutes after protamine
administration. The mean platelet count of 130,000/microliters before operation
remained stable, and no spontaneous platelet aggregation was observed in samples
of platelet-rich plasma obtained before cardiopulmonary bypass but after heparin
administration. Similarly, after heparin administration but before bypass,
platelet responsiveness to adenosine diphosphate remained unchanged when
compared with preoperative values. Plasma levels of platelet factor 4 increased
from 26 +/- 1 ng/ml (mean +/- standard error) to 843 +/- 383 ng/ml after heparin
administration but actually decreased throughout cardiopulmonary bypass to 52
+/- 25 ng/ml. Beta-thromboglobulin levels increased from 103 +/- 16 to 244 +/-
94 ng/ml with heparinization. The mean bleeding time was 10.5 minutes
preoperatively and 13.3 minutes postoperatively. The mean amount of
postoperative chest tube drainage (duration: 12 hours) was 432 +/- 67 ml. Thus,
despite the confirmed presence of heparin-dependent platelet-activating factor
in the plasma of these three patients, iloprost prevented heparin-induced
platelet activation during cardiopulmonary bypass while preserving platelet
function, as would be desired for postoperative hemostasis.
PMID: 2445042 [PubMed - indexed for MEDLINE]
126: Crit Rev Clin Lab Sci 1986;23(2):77-94
Clinical efficacy of heparin fractions: issues and answers.
Messmore HL.
The recent development of heparin fractions and fragments for clinical use has
created the prospect of some new agents at our disposal for the treatment of
thrombotic disorders. The development of a drug that will block thrombosis but
will not impair hemostasis now appears to be a possibility. Due to lack of
understanding of all of the mechanisms of the pathology of thrombosis, we are
not certain what the properties of the ideal anticoagulant should be. Of the
heparins and heparin fractions, fragments, and heparinoids now available to us,
we have yet to fully understand the mechanism of their pharmacologic activity.
It has been amply demonstrated that decreasing the average molecular weight
decreases the antithrombin activity while retaining the anti-Xa activity of
heparin derivatives. Studies on animal models have proven the antithrombotic
potency of some of these low molecular weight heparins to be equal to that of
unfractionated heparin. There has been some evidence that these fractions are
less likely than unfractionated heparin to cause hemorrhage in animal models as
well as in at least one human clinical trial. A recently published human
clinical trial revealed an unexpected incidence of hemorrhage following major
surgery when a certain heparin fraction was given as prophylaxis against
thrombosis. We are desperately in need of heparin derivatives, heparinoids or
other anticoagulants that can be used in place of standard heparin in patients
who are allergic to heparin or who have heparin-induced thrombocytopenia.
Patients with these problems not infrequently require cardiopulmonary bypass
surgery in which the use of heparin has been mandatory. There is now evidence
from animal and human studies that such a procedure is possible with a heparin
fraction or a heparinoid. This is true for hemodialysis as well. Studies in
progress offer hope that a low molecular weight fragment with potent anti-Xa
activity will not cause thrombocytopenia in patients with heparin-induced
thrombocytopenia. Whether this agent, a pentasaccharide, will have sufficient
antithrombotic potency for clinical use remains an important question. An
important property of some of the newer heparin fractions is a prolonged
duration of action which may permit fewer doses, thus reducing the cost as well
as patient discomfort and inconvenience.
Publication Types:
Clinical Trial
Review
PMID: 2419035 [PubMed - indexed for MEDLINE]
127: J Thorac Cardiovasc Surg 1985 Jun;89(6):950-1
Management of patients with heparin-induced thrombocytopenia requiring
cardiopulmonary bypass.
Long RW.
Publication Types:
Letter
PMID: 3999797 [PubMed - indexed for MEDLINE]
128: Anesthesiology 1985 Mar;62(3):363-5
Extracorporeal circulation in a patient with heparin-induced thrombocytopenia.
Smith JP, Walls JT, Muscato MS, McCord ES, Worth ER, Curtis JJ, Silver D.
PMID: 3872085 [PubMed - indexed for MEDLINE]
Last Updated: Saturday, June 7, 2003
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