An Inhibitor to Factor VIII Antigen Presenting as Acquired Von Willebrand Disease

A patient with clinical and laboratory evidence of acquired von willebrand disease is described. He presented with the recent onset of spontaneous hemorrhageand demonstrated a prolonged bleeding time, reduced factor VIII. C, and undetectable factor VIII:AG and factor VIIIR:WF. Following transfusion of cryoprecipitate, there was a smaller than expected immediate increase in factor VIII:C, factor VIIIR. WF and factor VIIIR. AG, with a rapid return to baseline levels, and no secondary rise in factor VIII:C. An inhibitor could be demonstrated in the patient’s plasma which markedly decreased the level of faotor viriRiAG in normal plasma while only weakly decreasing the activity of factor VIIIR. WF. Activity against factor VII1:C was demonstrable in vitro using a concentrated inhibitor preparation. The inhibitor was contained in the IgG fraction of plasma and lacked precipitating properties. This inhibitor, which demonstrates a specificity not previously seen in spontaneous anti-factor VIII antibodies, provides further evidence for the separate identity of the antigen and von Willebrand factor sites of the factor VIII molecule. It also indicates that inhibition of ristocetin-induced aggregation of platelets is not the most sensitive method for the detection of an inhibitor in all cases of acquired von Willebrand disease.