Lepirudin

Observational studies

Lepirudin has been used in patients with heparin-induced thrombocytopenia in a prospective study in 205 patients with 120 historical controls (HAT-3) and in a combined analysis of all HAT study data [ ]. Patients with laboratory-confirmed thrombocytopenia were treated with lepirudin in three different aPTT-adjusted dose regimens and during cardiopulmonary bypass. Mean lepirudin maintenance doses were 0.07–0.11 mg/kg/hour. End points were new thromboembolic complications, limb amputations, and death and major bleeding. The combined end point occurred in 43 (21%) of those treated with lepirudin; 30 died, 10 underwent limb amputation, and 11 had new thromboembolic complications. There was major bleeding in 40 patients, seven during cardiopulmonary bypass. Combining all the prospective HAT trials (n = 403), after the start of lepirudin treatment, the combined end point occurred in 82 patients (20%), with 47 deaths, 22 limb amputations, 30 new thromboembolic complications, and 71 episodes of major bleeding. Compared with the historical controls, the combined end-point after the start of treatment was significantly reduced (30% versus 52%), primarily because of a reduction in new episodes of thrombosis (12% versus 32%). Major bleeding was more frequent in the lepirudin-treated patients (29% versus 9.1%). Thus, the rate of new thromboembolic complications in patients with heparin-induced thrombocytopenia is low after lepirudin treatment. The rate of major bleeding of 18% might be reduced by reducing the starting dose to 0.1 mg/kg/hour.