Sequential Therapy with Activated Prothrombin Complex Concentrates and Recombinant Factor VIIa in the Treatment of Unresponsive Bleeding in Patients with Hemophilia and Inhibitors

Abstract 4664

The development of inhibitors to factor VIII or IX is the most common, severe, challenging and expensive complication of the treatment of patients with hemophilia. Hemophilia patients with inhibitors can develop bleeding episodes, which are refractory to monotherapy with either recombinant factor VIIa (rFVIIa) or activated prothrombin complex concentrates (APCC). Management of such bleeds is often difficult.

This report describes the results of a retrospective chart review of four hospitalized patients with severe hemophilia and inhibitors who have been treated with sequential doses of APCC and rFVIIa for refractory bleeding.

Sequential therapy was defined as the administration of both rFVIIa and APCC within 12 h. In 4 cases of patients with inhibitor, bleeding was not controlled by initial bypassing treatment. One patient had historical peak inhibitor titer increased to 1126 BU, and during peripheral inserted central catheter insertion for immune tolerance induction therapy, bleeding was not controlled. After APCC and rFVIIa were administered sequentially, bleeding was controlled. The second and third patients had bleeding problem after total knee replacement for hemophilic arthropathy, and two agents were administered sequentially. The last patient had small bowel resection because of intestinal obstruction, and post-operation bleeding was not controlled well. DIC was developed. Two agents were administered sequentially for bleeding problem and bleeding was controlled. Sequential therapy administration alternated one APCC dose to 1–2 rFVIIa doses: dosing intervals ranged between 3 and 6 h; APCC (75–100 U kg) was given every 12 h; rFVIIa (90 μg/ kg) was given every 3–6 h. Bleeding control was achieved in 12–24 h in all patients. Sequential therapy was discontinued after 2–5 days. No clinical adverse events were observed.

Sequential therapy with APCC and rFVIIa was efficacious without adverse events. A prospective clinical trial is needed to provide further evidence.