Argatroban Therapy in Women with Heparin-Induced Thrombocytopenia

Abstract

Women have increased risk of developing heparin-induced thrombocytopenia (HIT), a serious, immune-mediated prothrombotic condition, and have a worse prognosis when affected. We compared gender differences for treatment and outcomes in HIT patients administered argatroban therapy. From a multicenter retrospective registry of argatroban-treated patients, we identified females (n = 42) and males (n = 50) with clinically diagnosed HIT who were administered argatroban <or=10 microg/kg/min. Upon diagnosis of HIT, heparin was discontinued. Continuous intravenous argatroban was instituted, adjusted to achieve activated partial thromboplastin times (aPTTs) 1.5-3 times baseline. Between-gender comparisons were made of argatroban dosing, aPTT responses, and clinical outcomes (death, amputation, new thrombosis, major bleeding). At baseline, females and males were generally well matched, excepting platelet count (medians, 101 x 10(9)/L vs. 170 x 10(9)/L, p = 0.01), with 9 (21%) females and 19 (38%) males having HIT-related thrombosis. Typically, argatroban was initiated and maintained at 1.0-1.1 mug/kg/min for approximately 6 days, irrespective of gender. No differences were detected between females and males in aPTTs during therapy (respective medians, 57.3 vs. 59.5 seconds) or time to therapeutic aPTTs (7.3 vs. 10.3 hours), or platelet count recovery (2.5 vs. 7.4 days). Of patients with available data, 20 of 35 (57%) females and 19 of 35 (54%) males were converted to warfarin. The composite end point of death, amputation, or new thrombosis within 37 days of argatroban initiation occurred in 10 (24%) females and 8 (16%) males (p = 0.43). Within 37 days, 7 (17%) females and 7 (14%) males died (2 while on argatroban), 1 (2%) female required amputation (off argatroban), and 3 (7%) females and 2 (4%) males developed new thrombosis (3 while on argatroban). Major bleeding occurred in 1 (2%) female and 1 (2%) male. Argatroban can be used effectively and safely to manage HIT in females, with dosing requirements, aPTT responses, and clinical outcomes comparable to those in men. Future, larger studies are warranted in establishing the unique characteristics of HIT in females.