Lepirudin (recombinant hirudin) for parenteral anticoagulation in patientswith heparin-induced thrombocytopenia

Background-We prospectively investigated lepirudin for further parenteral a nticoagulation 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 tho se of historical control patients (n=120), Complete laboratory response (ac tivated partial thromboplastin time ratio >1.5 with less than or equal to 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 am putation (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 afte r HIT confirmation, fewer lepintdin-treated patients than historical contro l patients had experienced 11 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 (cum ulative incidence at 35 days, 44.6% versus 27.2%; RR 2.57; P=0.0001, log-ra nk test). No difference was observed in bleeding events requiring transfusi on (cumulative incidence at 35 days, 12.9% versus 9.1%; RR 1.66; P=0.23, lo g-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 p atients, Treatment should be initiated as soon as possible if HIT is suspec ted.