In Vivo Characteristics of rDNA Factor VIII: The Impact for the Future in Hemophilia Care

Abstract

In the late 1940’s and before, plasma was the only reliable source of blood clotting factors for replacement therapy. The physiological basis of plasma replacement therapy was initially worked out in canine models of classic hemophilia stressing the half life of Factor VIII, its distribution after infusion, and the maximal doses of Factor VIII that could be achieved in circulating blood. From this experience it became obvious that the maximal levels of Factor VIII that could be achieved with plasma were about 20% of normal or 0.2 u/ml [1]. Higher levels could not be attained because of the danger of inducing congestive heart failure. Although 20% levels of Factor VIII were sufficient to control hemarthroses, soft tissue bleeding and even major bleeding in some cases, this level was not always sufficient to control hemorrhage. Surgery, hematuria, and severe trauma to hemophilic patients frequently resulted in bleeding that required Factor VIII levels close to 100% of normal. Thus, the need for purified and concentrated Factor VIII products for classic hemophilic patients was never questioned. In fact, when plasma was the only therapeutic option, all clinical coagulationists agreed that for any clotting factor deficiencies, specific clotting factor concentrates were essential for treatment if normal hemostasis were to be achieved.

Supported in part by grants from the National Institutes of Health: HL26309, HL01922, HL07149, CA43447.