CONTINUOUS-INFUSION OF PORCINE FACTOR-VIII IN THE MANAGEMENT OF PATIENTS WITH FACTOR-VIII INHIBITORS

The effectiveness of continuous infusion porcine factor VIII (PFVIII) has been evaluated in the treatment of 7 consecutive patients with fac tor VIII(FVIII) inhibitors, Two patients had hemophilia A and five wer e nonhemophiliacs with acquired FVIII inhibitors. The median pretreatm ent anti-porcine FVIII titre was 0.2 (range: (0-15.0) Bethesda units ( BU), and the anti-human FVIII titer was 12.0 BU (range: 2.4-50.0), Ail patients presented with major bleeding, Patients were given a bolus d ose of PFVIII followed by continuous infusion, Six patients also recei ved immunosuppressive therapy. Therapeutic FVIII levels (>0.5 U/ml) we re achieved in 6 of 7 patients at a median time of 12.5 hr, and then m aintained with continuous infusion PFVIII. Six patients were treated f or more than 7 days, and in four of these there was a decline in FVIII recovery between days I to II, presumably related to a rising antibod y response to PFVIII. These four patients were plasmapheresed and the three patients with autoantibodies recovered therapeutic FVIII levels but this did not occur in the patient with hemophilia. Thrombocytopeni a developed in 4 patients at days 18 to 24, with the platelet count fa lling to 11 to 87 x 10(9)/L, and the PFVIII was discontinued in 3 pati ents, Ail patients recovered from the acute bleeding events, With prol onged immunosuppressive therapy, the FVIII inhibitor disappeared in ai l patients with autoantibodies and there have been no relapses after a median follow-up period of 581 days. This study demonstrates that con tinuous infusion PFVIII is an effective therapy for patients with FVII I inhibitors, but that prolonged treatment is associated with the deve lopment of inhibitors to porcine FVIII and severe thromhocytopenia, wh ich readily corrects with discontinuation of PFVIII. (C) 1997 Wiley-Li ss, Inc.