RECOMBINANT ACTIVATED FACTOR-VII (RFVIIA) THERAPY FOR INTRACRANIAL HEMORRHAGE IN HEMOPHILIA-A PATIENTS WITH INHIBITORS

We report the use of recombinant VIIa (rFVIIa) in the treatment of five ICHs in two factor VIII-deficient patients with inhibitors. In four of five ICHs, rFVIIa was the only factor replacement used at doses of 60-135 mu g/kg every 2-4 hr for 12-14 days. Hemostasis at the primary site of bleeding was achieved in all cases, and all patients survived with no permanent neurologic deficits. However, the patient who received the highest dose of rFVIIa during the first 4 days of therapy developed clinical symptoms consistent with a cerebral vascular accident of the brainstem characterized by acute onset of truncal ataxia and upward-gaze nystagmus on day 8 of rFVIIa therapy. While receiving rFVIIa therapy for treatment of these five ICHs, four treatment courses were complicated by bleeding at sites other than the primary site, including two episodes of localized oozing at central line insertion sites, two episodes of hemarthrosis, and two episodes of epistaxis. Antifibrinolytic therapy with tranexamic acid was effective in two of these episodes. Laboratory evaluation revealed shortening of the PT, variable shortening without normalization of the APTT, peak factor VII activity levels 7-30-fold higher than normal baseline values, and normal antithrombin III (ATIII) and alpha(2)-antiplasmin levels. In four of five ICHs, there was a 20-40% decrease in fibrinogen levels from baseline. The decrease in fibrinogen was accompanied by an increase in fibrin degradation products in 3/5 episodes and a 15-35% decrease in plasminogen activity levels in 2/5 episodes. Tissue factor pathway inhibitor (TFPI) levels remained stable and in the normal range. Although rFVIIa is an effective new therapy for the treatment of ICH in hemophilia patients with inhibitors, its optimal use with respect to safety and efficacy requires further clinical study. (C) 1994 Wiley-Liss, Inc.