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(Circulation. 1999;99:73-80.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Recombinant Hirudin (Lepirudin) Provides Safe and Effective Anticoagulation in Patients With Heparin-Induced Thrombocytopenia
A Prospective Study
From the Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt-University, Greifswald, Germany (A.G., P.E.); Behringwerke AG, Clinical Research Intensive Care, Marburg, Germany (H.V.); Department of Medicine I, RWTH, Aachen, Germany (U.J.); Department of Internal Medicine, William-Harvey Clinic, Bad Nauheim, Germany (V.H.-W.); Department of Internal Medicine, Justus-Liebig-University, Gießen, Germany (B.K.-M.); Centeon Pharma GmbH & Co, Biometry, Marburg, Germany (H.G.M.-V.); and Department for Haemostaseology and Transfusion Medicine, Kerckhoff-Clinic, Bad Nauheim, Germany (B.P.)
Correspondence to Prof Dr A. Greinacher, MD, Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt-University, Sauerbruchstr./Diagnostikzentrum, 17487 Greifswald, Germany. E-mail greinach{at}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 >109/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.
Key Words: heparin • platelets • thrombosis • trials • anticoagulants • immunology
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X. Song, G. Huhle, L. Wang, U. Hoffmann, and J. Harenberg Generation of Anti-Hirudin Antibodies in Heparin-Induced Thrombocytopenic Patients Treated With R-Hirudin Circulation, October 5, 1999; 100(14): 1528 - 1532. [Abstract] [Full Text] [PDF]
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S. Ahmad, W. P. Jeske, J. M. Walenga, D. A. Hoppensteadt, J. J. Wood, J.-M. Herbert, H. L. Messmore, and J. Fareed Synthetic Pentasaccharides Do Not Cause Platelet Activation by Antiheparin-Platelet Factor 4 Antibodies Clinical and Applied Thrombosis/Hemostasis, October 1, 1999; 5(4): 259 - 266. [Abstract] [PDF]
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H. L. Messmore JR Heparin-Induced Thrombocytopenia: Historical Review Clinical and Applied Thrombosis/Hemostasis, October 1, 1999; 5(1_suppl): S2 - S6. [Abstract] [PDF]
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W. P. Jeske, A. M. Jay, S. Haas, and J. M. Walenga Heparin-Induced Thrombocytopenic Potential of GAG and Non-GAG-Based Antithrombotic Agents Clinical and Applied Thrombosis/Hemostasis, October 1, 1999; 5(1_suppl): S56 - S62. [Abstract] [PDF]
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A. Greinacher, U. Janssens, G. Berg, M. Bock, H. Kwasny, B. Kemkes-Matthes, P. Eichler, H. Volpel, B. Potzsch, and M. Luz Lepirudin (Recombinant Hirudin) for Parenteral Anticoagulation in Patients With Heparin-Induced Thrombocytopenia Circulation, August 10, 1999; 100(6): 587 - 593. [Abstract] [Full Text] [PDF]
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 J. O. Ballard Anticoagulant-Induced Thrombosis JAMA, July 28, 1999; 282(4): 310 - 312. [Full Text] [PDF]
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