Argatroban Anticoagulant Therapy in Patients With Heparin-Induced Thrombocytopenia

Background —Heparin-induced thrombocytopenia (HIT) is an immune-mediated syndrome caused by heparin. Complications range from thrombocytopenia to thrombocytopenia with thrombosis. We report a prospective, historical- controlled study evaluating the efficacy and safety of argatroban, a direct thrombin inhibitor, as anticoagulant therapy in patients with HIT or HIT with thrombosis syndrome (HITTS). Methods and Results —Patients with HIT (isolated thrombocytopenia, n=160) or HITTS (n=144) received 2 μg · kg −1 · min −1 IV argatroban, adjusted to maintain the activated partial thromboplastin time 1.5 to 3.0 times baseline value. Treatment was maintained for 6 days, on average. Clinical outcomes over 37 days were compared with those of 193 historical control subjects with HIT (n=147) or HITTS (n=46). The incidence of the primary efficacy end point, a composite of all-cause death, all-cause amputation, or new thrombosis, was reduced significantly in argatroban-treated patients versus control subjects with HIT (25.6% versus 38.8%, P =0.014). In HITTS, the composite incidence in argatroban-treated patients was 43.8% versus 56.5% in control subjects ( P =0.13). Significant between-group differences by time-to-event analysis of the composite end point favored argatroban treatment in HIT ( P =0.010) and HITTS ( P =0.014). Argatroban therapy, relative to control subjects, also significantly reduced new thrombosis and death caused by thrombosis ( P <0.05). Argatroban-treated patients achieved therapeutic activated partial thromboplastin times generally within 4 to 5 hours of starting therapy and, compared with control subjects, had a significantly more rapid rise in platelet counts ( P =0.0001). Bleeding events were similar between groups. Conclusions —Argatroban anticoagulation, compared with historical control subjects, improves clinical outcomes in patients who have heparin-induced thrombocytopenia, without increasing bleeding risk