Precipitating antibodies in von Willebrand's disease

Abstract

WE report the presence of precipitating antibodies in three patients with von Willebrand's disease (VWD), an inherited deficiency of factor VIII (anti-haemophilic factor, AHF). To our knowledge this is the first description of patients with complete biological and immunological deficiency of a plasma-clotting protein responding to replacement therapy by the production of antibodies with properties indistinguishable from those elicited in animals. AHF is a high molecular weight (> 10⁶) glycoprotein complex¹ associated with two biological activities; one necessary for normal clotting (VIII: C) and the other for normal platelet function (Willebrand factor, VIIIR: WF). Specific antigenic determinants (VIIIR: AG) can be reliably quantified using heterologous antisera^2,3. Any concept of the structure or the molecular genetics of AHF needs to incorporate the clinical and immunological findings in the two congenital disorders associated with AHF deficiency: haemophilia A and VWD. The former is a sex-linked deficiency of VIII: C alone whereas the latter represents a deficiency of all three parameters of the AHF complex and is inherited as an autosomal trait. Non-precipitating antibodies to AHF, acquired after replacement therapy, are common in haemophilia A (ref. 4) but only one case has been reported in VWD^5,6.