Recombinant hirudin (Lepirndin) provides safe and effective anticoagulation in patients with heparin-induced thrombocytopenia -: A prospective study

Background-The immunological type of heparin-induced thrombocytopenia (HIT) is the most frequent drug-induced thrombocytopenia, This study evaluated the efficacy of recombinant hirudin (r-hirudin or lepirudin), a potent thrombin inhibitor, for anticoagulation in patients with confirmed HIT. Methods ann Results-Eighty-two patients in this prospective, multicenter study received 1 of 4 intravenous r-hirudin regimens: Al, HIT patients with thrombosis (n=51), 0.4-mg/kg bolus and then 0.15 mg.kg(-1).h(-1); A2, HIT patients with thrombosis receiving thrombolysis (n=5), 0.2-mg/kg bolus and then 0.1 mg.kg(-1).h(-1); B, HIT patients without thrombosis (n=18), 0.1 mg.kg(-1).h(-1) and C, during cardiopulmonary bypass surgery (n=8), 0.25-mg/kg bolus and then 5-mg boluses as needed. Response criteria were increase in platelet count by greater than or equal to 30% to >10(9)/L and activated partial thromboplastin time (aPTT) values 1.5 to 3.0 times baseline values achieved with a maximum of 2 dose increases, No placebo control was used for ethical reasons, Outcomes of a subset of r-hirudin-treated patients who met predefined inclusion criteria (n=71) were compared with those of a historical control group (n=120) for combined and individual incidences of death, amputations, new thromboembolic complications, and incidences of bleeding. Platelet counts increased rapidly in 88.7% of r-hirudin-treated patients with acute HIT. In regimens Al and A2, the 25% and 75% quartiles of the aPTT were within the target range at all but 1 time point. The incidence of the combined end point (death, amputation, new thromboembolic complications) was significantly reduced in r-hirudin patients compared with historical control patients (P=0.014). During first selected treatment, the adjusted hazard ratio for r-hirudin patients versus historical control was 0.279 (95% CI, 0.112 to 0.699; P=0.003). Bleeding rates were similar in both groups. Conclusions-r-Hirudin treatment is associated with a rapid and sustained recovery of platelet counts, sufficient aPTT prolongations, and true clinical benefits for patients with HIT.