Porcine Factor VIII in Factor VIII Antibody-Positive Hemophiliacs

Abstract

rected against the factor VIII protein, and completely or partially neutralizing the plasma coagulant activity of the clotting factor, is associated with a variety of diseases, and these antibodies are often the cause of the life-threatening bleeds. Such inhibitors, designated as acquired hemophilia, are uncommon (found in 0.2-1.0 previously normal individuals per million population annually), but 37% of those who develop them suffer from serious bleeds, and at least 22% die. This morbidity and mortality can be reduced by early laboratory detection, familiarity with the clinical manifestations, and the availability and use of an appropriate treatment. Unfortunately, none of the available therapeutic approaches is universally effective, and most are associated with potentially serious side effects. Recently, there has been interest in polyelectrolyte-fractionated porcine factor VIII concentrate (Porton Speywood Ltd, Wrexham, UK) for the treatment of acquired factor VIII autoantibodies. This product carries no risk of contamination with human pathogenic blood-borne viruses such as human immunodeficiency virus (HIV) and hepatitis B and C, but more importantly, it cross-reacts only to a slight extent with even high concentrations of anti-human factor VIII antibodies. This makes it easy to monitor its efficacy in terms of the resulting levels of plasma factor VIII in treated patients. The International Acquired Hemophilia Study Group has evaluated treatment with porcine factor VIII concentrate in 65 patients from North America and Europe with acquired hemophilia. These were all well characterized clinically and in terms of laboratory tests. Their median age was 62 years (range 18-82), with a preponderance of older individuals, and an even sex distribution. Over 50% had no predisposing disease that was obviously responsible for their acquired hemophilia; the remainder had covert or overt collagen vascular or autoimmune diseases (17%), solid malignant tumors (12%), pregnancy or post partum states (11%), medication toxicities (6%), or lymphoproliferative malignancies (1.5%). Younger patients predominantly had complications of pregnancy or collagen vascular disease