Release of Factor VIII (Antihaemophilic Factor) from Perfused Organs and Tissues

Abstract

IT has been known for many years that patients with classic haemophilia bleed because they lack a plasma factor required for normal blood coagulation. This factor, factor VIII (antihaemophilic factor) of normal plasma, has been extensively investigated, but its exact site of origin is unknown. Recent developments in organ transplantation have stimulated us to look for the specific organ source of this procoagulant. If the site of synthesis of factor VIII could be identified, permanent replacement of the deficient factor in haemophilia might be possible. In the past, a variety of experimental approaches has been used to investigate the body's mechanisms for maintaining haemostatic levels of factor VIII: organ ablation¹, total body irradiation², administration of hepatotoxins^3,4, reticulo-endothelial blockade⁵, physical exercise⁶, hormone administration⁷, and thromboplastin injections⁴. Several recent investigations have suggested that the spleen may play a part in the regulation of concentrations of factor VIII in the plasma of normal individuals. Weaver et al. demonstrated that factor VIII is maintained at normal concentrations when intact normal dogs are crosscirculated with haemophilic dogs, but that the concentrations decrease if a splenectomy is first performed on the normal animals⁸. In humans, Libre et al.⁹ have observed that splenectomy abolishes the rise in factor VIII that is known to follow injection of adrenaline into normal subjects¹⁰. Pool was able to recover antihaemophilic activity in extracts of splenic tissue, but not from a variety of other tissues¹¹.