Effects of argatroban therapy, demographic variables, and platelet count on thrombotic risk in heparin-induced thrombocytopenia

Abstract

Conclusion: Argatroban provides excellent antithrombotic therapy in patients with heparin-induced thrombocytopenia (HIT). Summary: The authors evaluated thrombotic risk of HIT with respect to the effects of argatroban, a direct thrombin inhibitor, patient demographics, and platelet count. This was a retrospective study designed to analyze thrombotic outcomes in 882 patients with HIT, of whom 697 patients who received argatroban at doses of 1.7 to 2.0 μg/(kg · min) for 5 to 7 days. These patients were compared with 185 historical control subjects from a previously reported prospective study. The primary end point was a composite time-to-event analysis that included death owing to thrombosis, a new thrombosis ≤37 days, and amputation secondary to HIT-associated thrombosis. Individual components of the primary end point were also analyzed, and hazard ratios were estimated for treatment with and without adjustments for baseline platelet count, race, weight, gender, and age. Compared with control subjects, argatroban significantly reduced the thrombotic composite end point (HIT: hazard ratio, 0.33; 95% confidence interval, 0.20 to 0.54; P < .001). For HIT with thrombosis, the hazard ratio for treatment with argatroban was 0.39 (95% confidence interval, 0.25 to 0.62; P < .001). There was no influence of covariant adjustments. More patients taking argatroban remained free of thrombotic events during follow-up than did control subjects. This was independent of whether baseline thrombosis was present or absent. Argatroban also significantly reduced new thrombosis (P < .001) and death due to thrombosis (P < .001). The control group and the argatroban-treated group had similar major bleeding episodes (6% to 7%, P = .74). Nonwhite patients had a two times greater risk of thrombotic events. Thrombotic risks were also increased 1.7 times in women vs men with HIT and thrombosis. Thrombotic events were also increased with decreasing weight or decreasing platelet count. Comment: This study confirms the effectiveness of argatroban in treating HIT. Note that HIT patients with lower body weight and more severe thrombocytopenia, as well as those who were nonwhite, had greater HIT-associated thrombotic complications.