(Circulation. 1999;100:587-593.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Lepirudin (Recombinant Hirudin) for Parenteral Anticoagulation in Patients With Heparin-Induced Thrombocytopenia
From the Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt University, Greifswald (A.G., P.E.); Department of Medicine-I, Rheinisch-Westfälische Technische Hochschule, Aachen (U.J.); Department of Medicine-III, University Hospitals, Homburg/Saar (G.B.); Institute for Transfusion Medicine, Otto-von-Guericke University, Magdeburg (M.B.); Biometrics Department, Centeon Pharma GmbH, Marburg (H.K.); Department of Medicine, Justus-Liebig University, Gießen (B.K.-M.); Chiron-Behring-GmbH, Marburg (H.V.); Department for Transfusion Medicine and Hemostasis Research, Kerkhoff Klinik, Bad Nauheim (B.P.); and Development, Hoechst Marion Roussel Deutschland GmbH, Frankfurt (M.L.), Germany.
Correspondence to Prof Dr Andreas Greinacher, Institute for Immunology and Transfusion Medicine, Klinikum/Sauerbruchstraße, Ernst-Moritz-Arndt University, Sauerbruchstraße/Diagnostikzentrum, D-17487 Greifswald, Germany. E-mail greinach{at}mail.uni-greifswald.de
Background—We prospectively investigated lepirudin for further parenteral anticoagulation in patients with heparin-induced thrombocytopenia (HIT).
Methods and Results—Patients with confirmed HIT (n=112) received
lepirudin according to need for 2 to 10 days (longer if necessary): A1,
treatment: 0.4 mg/kg IV bolus, followed by 0.15 mg ·
kg-1 · h-1 intravenous
infusion, n=65; A2, treatment in conjunction with
thrombolysis: 0.2 mg/kg, followed by 0.10 mg ·
kg-1 · h-1, n=4; and B, prophylaxis:
0.10 mg · kg-1 · h-1, n=43.
Outcomes from 95 eligible lepirudin-treated patients were compared with
those of historical control patients (n=120). Complete laboratory
response (activated partial thromboplastin time ratio >1.5
with 
2 dose increases and platelet count normalization by day 10)
was achieved in 65 lepirudin-treated patients (69.1%; 95% CI, 59.3%
to 78.3%). At 2 weeks after cessation of lepirudin, 11 patients died
(9.8%), 10 underwent limb amputation (8.9%), and 20 suffered a new
thromboembolic complication (17.9%). The average combined event rate
per patient-day decreased from 5.1% in the pretreatment period to
1.5% in the treatment period. Thirty-five days after HIT confirmation,
fewer lepirudin-treated patients than historical control patients had
experienced 
1 outcome (cumulative incidence 30.9% versus 52.1%;
relative risk [RR] 0.71; P=0.12, log-rank test).
Bleeding events were more frequent in the lepirudin group than the
historical control group (cumulative incidence at 35 days, 44.6%
versus 27.2%; RR 2.57; P=0.0001, log-rank test). No
difference was observed in bleeding events requiring transfusion
(cumulative incidence at 35 days, 12.9% versus 9.1%; RR 1.66;
P=0.23, log-rank test); no intracranial bleeding was
observed in the lepirudin group.
Conclusions—Lepirudin effectively prevents death, limb amputations, and new thromboembolic complications and has an acceptable safety profile in HIT patients. Treatment should be initiated as soon as possible if HIT is suspected.
Key Words: heparin • thrombocytopenia • lepirudin • platelets • hirudin
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