Lepirudin in patients with heparin-induced thrombocytopenia - results of the third prospective study (HAT-3) and a combined analysis of HAT-1, HAT-2, and HAT-3

Objectives: To assess efficiency and safety opf lepirudin in patients wit heparin-induced thrombocytopenia (HIT) in a prospective study data. Patients/methods: Patients with laboratory-confirmed HIT were treated with lepirudin in three different aPTT-adjusted dose regimen and during cardiopulmonary bypass (CPB). Endpoints were new thromboembolic compilations (TEC), limb amputations, and death and major bleeding. A historical control group (n = 120) was used for comparison. Results: After start of lepirudin in 205 patients treated in HAT-3, the combined endpoints occured in 43 (21.0%). Thirty (14.6%) patients died, 10 (4.9%) underwent limb amputation, and 11 (5.4%) new TECs occured. Major bleeding occured in 40 patients (19.5%) (seven during CPB surgery). Combining all prospective HAT trials (n = 403), after start lepirudin treatment, the combined endpoints occured in 82 patients (20.3%), with 47 deaths (11.7%), 22 limb amputations (5.5%), 30 new TECs (7.4%), and 71 (17.6%) major bleedings. Compared with historical control group (log-rank test), the combined endpoints after start of treatment was reduced (26.7% vs. 52.1%, P = 0.0473), primarily because of reduction in new thromboses (11.9% vs. 32.1%, P = 0.0008). Mean lepirudin maintenance doses ranged from 0.07 to 0.11 mg kg(-1) h(-1). Major bleeding was more frequent in the lepirudin treatment. The rate of major bleeding of 17.6% might be reduced by reducing the starting dose to 0.1 mg kg(-1) h(-1).