Argatroban anticoagulant therapy in patients with heparin-induced thrombocytopenia

Background-Heparin-induced thrombocytopenia (HIT) is an immune-mediated syn drome caused by heparin. Complications range from thrombocytopenia to throm bocytopenia 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 KIT or HIT with thromb osis syndrome (HITTS). Methods and Results-Patients with HIT (isolated thrombocytopenia, n=160) or HITTS (n=144) received 2 mug . kg(-1) . min(-1) TV argatroban, adjusted to maintain the activated partial thromboplastin time 1.5 to 3.0 times baseli ne value. Treatment was maintained for 6 days, on average. Clinical outcome s over 37 days were compared with those of 193 historical control subjects with KIT (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 thromb osis, was reduced significantly in argatroban-treated patients versus contr ol 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 subject s, also significantly reduced new thrombosis and death caused by thrombosis (P<0.05). Argatroban-treated patients achieved therapeutic activated parti al thromboplastin times generally within 4 to 5 hours of starting therapy a nd, 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 su bjects, improves clinical outcomes in patients who have heparin-induced thr ombocytopenia, without increasing bleeding risk.