The in vitro cross-reactivity and blood coagulation potential of recombinant porcine factor VIII in Japanese patients with acquired hemophilia A.

Abstract

Recombinant porcine factor VIII (rpFVIII) is a hemostatic agent for acquired hemophilia A (AHA). Cross-reaction of auto-antibodies against rpFVIII has been reported, although no data are available in Japanese patients. This study investigated the cross-reactivity and coagulation potential of rpFVIII in plasma samples from Japanese patients with AHA. Cross-reactivity was calculated as the ratio of anti-porcine FVIII inhibitor titer (pFVIII-INH) to human FVIII inhibitor titer. Comprehensive coagulation potential was assessed by clot waveform analysis (CWA) and thrombin generation assay (TGA) in samples spiked with rpFVIII (equivalent to 200 U/kg). Nine of 16 plasma samples (56.3%) had positive pFVIII-INH, with a median cross-reactivity of 1.2%. FVIII activity (FVIII:C) was restored to > 100% in all samples upon spiking with rpFVIII, but was weakly correlated with pFVIII-INH. CWA parameters and most TGA parameters were restored to normal upon spiking with rpFVIII; correlation of these parameters with FVIII:C was similar to that observed in controls. Overall, cross-reactivity to rpFVIII in Japanese patients was similar to that reported in Caucasian patients. Our results suggest that an initial clinical dose of 200 U/kg rpFVIII could restore coagulation potential to normal, and that FVIII:C monitoring after rpFVIII administration may be more informative than pFVIII-INH before administration.