Effects of Argatroban Therapy, Demographic Variables, and Platelet Count on Thrombotic Risks in Heparin-Induced Thrombocytopenia

Abstract

We investigated the effects of the direct thrombin inhibitor argatroban, patient demographics, and the platelet count on thrombotic risks in heparin-induced thrombocytopenia (HIT), a serious thrombotic condition, to determine if argatroban provides effective antithrombotic therapy in patients with HIT without increasing bleeding. We retrospectively analyzed thrombotic outcomes in 882 HIT patients (697 patients receiving mean argatroban doses of 1.7 to 2.0 mug/kg/min for 5 to 7 days, plus 185 historical control subjects) from previously reported prospective studies. Time-to-event analyses of our primary end point-a thrombotic composite of death due to thrombosis, amputation secondary to HIT-associated thrombosis, or new thrombosis within 37 days-and the individual components were conducted, with hazard ratios estimated for treatment with and without adjustments for patient age, gender, race, weight, and baseline platelet count. Argatroban, vs control, significantly reduced the thrombotic composite risk (HIT: hazard ratio, 0.33; 95% confidence interval [CI], 0.20 to 0.54, p < 0.001; HIT with thrombosis: hazard ratio, 0.39; 95% CI, 0.25 to 0.62, p < 0.001), regardless of covariate adjustments. More argatroban-treated patients than control subjects remained thrombotic event free during follow-up, regardless of whether baseline thrombosis was absent (91% vs 73%) or present (72% vs 50%). Argatroban significantly reduced new thrombosis (p < 0.001) and death due to thrombosis (p </= 0.001). Major bleeding was similar between groups (6 to 7%, p = 0.74). Thrombotic risks were 2 times greater in nonwhite than in white patients, 1.7 times greater in female than male patients with HIT and thrombosis, and increased with decreasing weight or platelet count. Argatroban, vs control, provides effective antithrombotic therapy in patients with HIT, without increasing bleeding. Patients at higher risk for HIT-associated thrombosis include women, nonwhites, and individuals with current HIT-associated thrombosis, lower body weight, or more severe thrombocytopenia.