Activation of low molecular weight fragment of antihaemophilic factor (factor VIII) by thrombin

Abstract

THE precise molecular function of plasma antihaemophilic factor (AHF, factor VIII), a glycoprotein with an apparent molecular weight of 2 × 10⁶, is unknown. Recent experiments suggest that this function may be carried out by a low molecular weight (LMW) fragment which can be dissociated from plasma AHF by increased salt concentration^1–3. The LMW fragment retains procoagulant activity, but is not reactive in immunoprecipitation assays for AHF-related antigen⁴. A high molecular weight (HMW) fragment, also identified using high salt conditions, has no procoagulant activity but retains AHF-related antigen in immunoprecipitation assays and von Willibrand factor activity in washed platelet assays^4,5. We have now found that the LMW fragment, as well as AHF^6–9, is susceptible to activation by thrombin. This observation suggests that the LMW fragment is not a product of thrombin activation of AHF and verifies the proposed role of the LMW fragment in AHF procoagulant activity.