The effectiveness of continuous infusion porcine factor VIII (PFVIII) has been evaluated in the treatment of 7 consecutive patients with factor VIII(FVIII) inhibitors. Two patients had hemophilia A and five were nonhemophiliacs with acquired FVIII inhibitors. The median pretreatment 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). All patients presented with major bleeding. Patients were given a bolus dose of PFVIII followed by continuous infusion. Six patients also received immunosuppressive therapy. Therapeutic FVIII levels (>0.5 U/ml) were achieved in 6 of 7 patients at a median time of 12.5 hr, and then maintained with continuous infusion PFVIII. Six patients were treated for more than 7 days, and in four of these there was a decline in FVIII recovery between days 7 to 11, presumably related to a rising antibody 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. Thrombocytopenia developed in 4 patients at days 18 to 24, with the platelet count falling to 11 to 87 × 10 9 /L, and the PFVIII was discontinued in 3 patients. All patients recovered from the acute bleeding events. With prolonged immunosuppressive therapy, the FVIII inhibitor disappeared in all patients with autoantibodies and there have been no relapses after a median follow-up period of 581 days. This study demonstrates that continuous infusion PFVIII is an effective therapy for patients with FVIII inhibitors, but that prolonged treatment is associated with the development of inhibitors to porcine FVIII and severe thrombocytopenia, which readily corrects with discontinuation of PFVIII. Am.

The stability of porcine factor VIII (Hyate:C(®) ) 30 units mL(-1) , 15 units mL(-1) and 5 units mL(-1) prepared aseptically in 0.9% sodium chloride injection was studied. Solutions were stored in plastic syringes at room temperature and ambient light, and at body temperature protected from light. Samples obtained immediately after mixing and at 4, 24, 48 and 72 h were assayed for FVIII activity using a one-stage FVIII assay. Samples were considered stable if FVIII activity did not decline more than 10% compared with baseline values. Hyate:C(®) 5 units mL(-1) stored at room temperature retained FVIII activity within 90% of baseline values for at least 24 h. When stored at body temperature, FVIII activity of Hyate:C(®) 5 units mL(-1) declined to less than 90% of baseline values within 4 h. Stability of Hyate:C(®) 15 units mL(-1) and 30 units mL(-1) stored at room temperature was retained for at least 72 h. When Hyate:C(®) 15 units mL(-1) and 30 units mL(-1) were stored at body temperature, stability was retained for 24 h. Results of this study will permit further evaluation of Hyate:C(®) stability when administered by ambulatory infusion pumps.

The effectiveness of continuous infusion porcine factor VIII (PFVIII) has been evaluated in the treatment of 7 consecutive patients with factor VIII(FVIII) inhibitors. Two patients had hemophilia A and five were nonhemophiliacs with acquired FVIII inhibitors. The median pretreatment 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). All patients presented with major bleeding. Patients were given a bolus dose of PFVIII followed by continuous infusion. Six patients also received immunosuppressive therapy. Therapeutic FVIII levels (>0.5 U/ml) were achieved in 6 of 7 patients at a median time of 12.5 hr, and then maintained with continuous infusion PFVIII. Six patients were treated for more than 7 days, and in four of these there was a decline in FVIII recovery between days 7 to 11, presumably related to a rising antibody 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. Thrombocytopenia developed in 4 patients at days 18 to 24, with the platelet count falling to 11 to 87 × 10 9 /L, and the PFVIII was discontinued in 3 patients. All patients recovered from the acute bleeding events. With prolonged immunosuppressive therapy, the FVIII inhibitor disappeared in all patients with autoantibodies and there have been no relapses after a median follow-up period of 581 days. This study demonstrates that continuous infusion PFVIII is an effective therapy for patients with FVIII inhibitors, but that prolonged treatment is associated with the development of inhibitors to porcine FVIII and severe thrombocytopenia, which readily corrects with discontinuation of PFVIII. Am.

A is an X-linked disorder caused by absent or dysfunctional factor VII1:C.Because of therapy-induced complications: hepatitis, inhibitor formation, and infection with Human Immunodeficiency Virus, CS determination is often requested. CS by analysis of factor VII1:C levels and pedigree-derived probabilities has limited utility and significant risk for error. We evaluated the utility of 3 intraqenic restriction fragment length polymorphisms (RFLPs) (Intron 18, 22 and 2 5 ) and the closely-linked extragenic RFLP (ST14) to provide CS through genotype assignment. Using standard Southern blots we found that 3 8 / 9 3 ( 4 1 % ) , 2 5 / 4 3 ( 5 8 % ) , 1 4 / 4 4