The Evidence behind Inhibitor Treatment with Porcine Factor VIII

Abstract

Factor VIII auto- and alloantibodies neutralise porcine factor VIII to a lesser extent than factor VIII of human origin. The reduced reactivity of the porcine molecule, predominantly due to sequence variation in the A2 and C2 domains, has been the rationale for using porcine factor VIII to secure haemostasis for patients with factor VIII inhibitors. Porcine factor VIII has been shown to provide effective haemostatic control particularly for patients with intermediate inhibitor titres with limited porcine cross-reactivity. Small studies have indicated porcine factor VIII can be associated with desensitisation of some factor VIII inhibitor patients. Porcine factor VIII has been shown to produce mild platelet agglutination, an effect that may enhance its efficacy. Adverse reactions are dose-related and do not preclude safe and effective long-term home use for the subgroup of inhibitor patients with modest or absent anamnestic response. Efforts to secure source plasma free of viral markers, particularly porcine parvovirus, have limited the supply of this therapeutic product.

B-Cell and T-Cell Epitopes in Anti-factor VIII Immune Responses

“…Plasma-derived porcine FVIII has been used to treat allo-immune inhibitor patients who fail tolerance induction [110], and a recombinant porcine FVIII has been produced and is being characterized [111,112]. The Lollar lab has shown that in many immune responses to factor VIII there is only limited cross-reactivity between anti-human FVIII inhibitory antibodies and porcine FVIII [113], and this lack of antigenic cross-reactivity has been exploited to map B-cell epitopes within particular domains or regions of FVIII using porcine-human hybrid molecules [95,114].…”

Current difficulties and recent advances in bypass therapy for the management of hemophilia with inhibitors: a new and practical formulation of recombinant factor VIIa

“…Historically, porcine factor VIII (pFVIII) has been used as an alternative to human-derived concentrates in patients with an inhibitor to factor VIII 8. pFVIII has been observed to be 80% to 90% effective in patients with factor VIII inhibitors due to the low cross-reactivity to pFVIII 9–11.…”

Coagulation Factor Preparations

“…19,20 Levels and potency of anti-factor VIII antibody inhibitors can be determined by a Bethesda assay. Thus, in a hemophilia A patient who has formed anti-human factor VIII antibodies, or in a patient with an autoantibody against factor VIII, porcine factor VIII may circumvent such an inhibitor.…”