Recombinant Porcine Factor VIII in Patients with Acquired Hemophilia A: Single-Center Experience and Dosing Strategy

Introduction Treatment of bleeds in patients with acquired hemophilia A (AHA) with bypassing agents is often difficult and unpredictable. Monitoring of the effect in routine clinical practice is not possible. A recombinant porcine factor VIII B-domain-deleted product (rpFVIII; OBIZUR) is approved for the treatment of bleeding episodes in adults with AHA. The recommended high initial dose of 200 IU/kg body weight is a matter of debate. We report our approach to the treatment of patients with AHA with rpFVIII.

Methods A retrospective chart review of all patients with AHA treated with rpFVIII at our institutions from April 2016 to September 2019.

Results Major bleeds in 12 patients (median age: 78 years, range: 38–92) were treated with rpFVIII. In one bleed (gastrointestinal following unsatisfactory bypassing agent therapy), rpFVIII was second-line treatment, and in 12 bleeds (mainly muscle and soft-tissue bleeds) it was first-line treatment. Good hemostatic efficacy was seen in 12 bleeds. rpFVIII loading doses of 50 U/kg bodyweight increased FVIII activity to sufficient levels between 55 and 112% within 1 hour. Subsequent median doses were two times 25 to 50 U rpFVIII/kg body weight/day for 1 and 7 days to maintain a factor VIII trough level above 30%. Duration of treatment was adjusted as per the type of bleeding. No rpFVIII-related adverse events were reported. Two patients died in the hospital (one due to sepsis and another due to pneumonia after aspiration). All patients received 1 g of tranexamic acid three to four times daily concomitantly and prednisolone for immunosuppression. One out of 12 patients received an rpFVIII loading dose of 100 U/kg body weight due to a life threatening throat and tongue bleed. In this case, we observed no increase in FVIII activity (1% at baseline to 2% after 1 hour) and treatment was switched to bypassing agents. Measurement of the rpFVIII inhibitor titer later on revealed an antiporcine titer of 13.8 BU (human titre: 4.8 BU). All other patients had no relevant cross-reactivity and antiporcine titers between 0.4 and 0.8 BU, if done.

Conclusion rpFVIII showed good hemostatic efficacy in 12/13 bleeds in 10/12 patients with much lower doses than in the registration study. We recommend an initial dose of 50 U rpFVIII/kg body weight and the monitoring of factor VIII levels to adapt to the dose. In case of no or low increase of factor VIII levels, relevant rpFVIII inhibitor titres are likely and further treatment with bypassing agents should be considered.

Publication History

Article published online:
13 November 2020