Porcine factor VIII provides clinical benefit to patients with high levels of inhibitors to human and porcine factor VIII.
The development of an inhibitor against Factor VIII is an important complication of haemophilia and occurs in approximately 31% of patients [1]. Despite various approaches to their management, the presence of these inhibitors remains a major cause of morbidity and mortality. Inhibitors may be low level [<5 Bethesda Units (BU)] or high level [>10 BU]. Low-level inhibitors usually remain low and do not respond to administered factor VIII with a rise of the inhibitor titre; high-level inhibitors, in contrast, are characterized by a rapid rise in titre following treatment with factor VIII. Modalities of treatment of acute bleeding episodes in patients with inhibitors include 'overcoming' the inhibitor with very large doses of factor VIII, 'bypassing' the inhibitor blockade with products such as activated prothrombin complex concentrates or recombinant factor VIIa, 'removing' the inhibitor by plasmapheresis or immunoabsorption and 'repressing' it with immunosuppressive drugs and immune tolerance induction. An alternative approach is to use a porcine factor VIII concentrate which does not cross-react with the human factor VIII inhibitor. Following treatment with porcine factor VIII, functional factor VIII can be detected and the therapeutic levels correlate with cessation of bleeding. The use of porcine factor VIII may, however, result in the development of antiporcine factor VIII antibodies, limiting its use. Experience in patients with high-titre inhibitors indicates that porcine factor VIII therapy could be used in the presence of factor VIII inhibitors [2-11], including inhibitors to porcine factor VIII [5,7], and that haemostasis may be obtained in the absence of detectable levels of circulating factor VIII [7,11].
Gribble
J
J
Albuquerque, New Mexico, USA.
Garvey
M B
MB
D000818:Animals; D000910:Antibodies, Heterophile / Q000097:blood; D002675:Child, Preschool; D005169:Factor VIII / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D006467:Hemophilia A / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D006470:Hemorrhage / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D007223:Infant; D007518:Isoantibodies / Q000097:blood*; D008297:Male; D013552:Swine / Q000276:immunology; D013921:Thrombocytopenia / Q000139:chemically induced
D000910:Antibodies, Heterophile; D007518:Isoantibodies; D005169:Factor VIII