Cross-reacting recombinant porcine FVIII inhibitors in patients with acquired haemophilia A.

Abstract

Acquired haemophilia A (AHA) is a rare bleeding disorder caused by the development of autoantibodies to endogenous human factor VIII (hFVIII). If treatment of bleeding is required, one option is recombinant porcine FVIII (rpFVIII). Cross-reactivity between factor VIII inhibitors and rpFVIII has previously been described. The aim of this study was to retrospectively assess the incidence of cross-reacting anti-porcine inhibitors in patients diagnosed with AHA in two UK centres. The plasma of fifty-one patients diagnosed with AHA via reduced FVIII:C and positive FVIII inhibitor titre as detected with a Nijmegen-Bethesda assay (NBA) was also tested by a porcine Bethesda assay (PBA). The NBA was modified by replacement of human FVIII with rpFVIII in the PBA, with determination of residual FVIII by one-stage clotting assay. The median FVIII inhibitor titre by NBA was 22.8 BU/mL (range: 0.8-1000 BU/mL). 37% of samples exhibited linear, type 1 kinetics in the NBA. Negative PBA was observed in 26 patients, and 25 were positive (median PBA: 3.5 BU/mL; range: 0.8-120 BU/mL). Type 1 kinetics were observed in 40% of PBA-positive patients. At NBA tires of greater than 100 BU/mL, the positive predictive value for the presence of porcine cross-reactivity was 100%. At NBA below 5 BU/mL, the negative predictive value for the presence of porcine cross-reactivity was 71%. Cross-reactivity between FVIII inhibitors and rpFVIII was observed in 49% of patients. The presence of inhibitors to rpFVIII may influence the treatment choice for patients with acquired haemophilia A.