Development and present status of concentrate therapy for hemophilia and von Willebrand's disease.

A brief review of the current status of treatment of two severe bleeder diseases, hemophilia A and von Willebrand's disease, with factor VIII concentrate is given. The functional activities deficient in the two diseases, antihemophilic factor (AHF) or coagulant factor VIII (F. VIII:C) in hemophilia, and the von Willebrand factor(s) (vWF; F.VIII R: Ag) in von Willebrand's disease, are present in a very large protein moiety of plasma, the macromolecular factor VIII complex. The rationale for replacement therapy of hemophilia depends on assessment of the severity of a given hemorrhagic episode followed by single, multiple, or continuous infusions of factor VIII concentrates sufficient to raise the plasma AHF to the hemostatic level (15 - less than 50%, depending on the severity of hemorrhage). Prophylactic regimens prevent hemorrhage but are expensive. Despite many problems in their use, the success of factor VIII concentrates in controlling severe hemorrhage and in preventing crippling by arthropathies is evident in many ways including the demand for concentrates, which now exceed the economic value of two other main products of plasma fractionation, albumin and gamma globulin. The rationale for therapy of von Willebrand's disease is dependent on the formation of the hemostatic platelet plug, which includes adhesion of platelets to a vascular site of bleeding, followed by platelet aggregation to give the hemostatic thrombus. The very large molecular weight arrays of the factor VIII complex contained in cryoprecipitate appear needed for development of the hemostatic plug. A new test for determining the plasma platelet-aggregating vWF, the Botrocetin test, appears superior to the ristocetin test. An activator factor in Bothrops snake venom is used. Some prospects for improving the factor VIII therapeutic preparations through recombinant DNA technology and through altering procedures for fractionation are outlined.