Factor VIII is a compound of high molecular weight which interacts with activated factor IX, calcium, and phospholipid to generate thromboplastin (activated factor X) for blood coagulation. It has the electrophoretic mobility of an α-2 globulin, and probably consists of both glycoprotein and phospholipid. It is released into the circulation by both the liver and the spleen. Factor VIII is quite labile, with a halflife of only 12 hr. The inheritance of the factor is mediated by both X-linked and autosomal chromosomes. Defects in the former give rise to classical hemophilia, and in the latter to von Willebrand's disease and several variants of hemophilia. Serious traumatic or surgical bleeding in patients with these disorders is currently controlled by the administration of factor VIII concentrates. These concentrates are generally available and their use has resulted in substantial improvement in both the duration and quality of life. An unresolved problem has been the appearance of antibodies to factor VIII, both in treated hemophiliacs and in patients with a variety of other clinical disorders. The plasma concentration of factor VIII is influenced by several hormones including thyroxine, progesterone, corticosteroids, and epinephrine, and varies considerably from individual to individual. Increased levels are found in several diseases with prominent thromboembolic complications. The role of factor VIII in promoting hypercoagulability is uncertain, its metabolic pathways are unknown, and its physical concentration, apart from its coagulant activity, unmeasured. The introduction of several new techniques for characterizing the factor promises to improve our knowledge.
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