(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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