Lepirudin (recombinant hirudin) for parenteral anticoagulation in patients with heparin-induced thrombocytopenia. Heparin-Associated Thrombocytopenia Study (HAT) investigators.
BACKGROUND
We prospectively investigated lepirudin for further parenteral anticoagulation in patients with heparin-induced thrombocytopenia (HIT).


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.
Greinacher
A
A
Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany. greinach@mail.uni-greifswald.de
Janssens
U
U
Berg
G
G
Böck
M
M
Kwasny
H
H
Kemkes-Matthes
B
B
Eichler
P
P
Völpel
H
H
Pötzsch
B
B
Luz
M
M
D000368:Aged; D000671:Amputation, Surgical / Q000706:statistics & numerical data; D000925:Anticoagulants / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000188:drug therapy*; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D006493:Heparin / Q000009:adverse effects*; D024764:Hirudin Therapy; D006629:Hirudins / Q000031:analogs & derivatives*; D006801:Humans; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D012449:Safety; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced / Q000188:drug therapy*; D013927:Thrombosis / Q000150:complications / Q000188:drug therapy / Q000401:mortality; D016896:Treatment Outcome
D000925:Anticoagulants; D006629:Hirudins; D011994:Recombinant Proteins; D006493:Heparin; C083544:lepirudin