A patient with acquired variant von Willebrand's disease was given an infusion of 2000 units of high purity porcine factor VIII (Hyate). Quantitative factor VIII parameters were assessed following infusion and human factor VIII multimers were analysed by radioimmunoelectrophoresis and autoradiography. We have previously described the patient to have acquired von Willebrand's disease due to a circulating inhibitor to the factor VIII complex (B. J. Haematol-, 54,233,1983). Prior to infusion plasma from the patient contained factor VIIIC, RRCo, and vWFAg at less than 10 u/dl- Plasma factor VIII multimers showed an abnormal pattern with no high molecular weight bands present despite a normal triplet structure in the low molecular weight forms. After the infusion of porcine factor VIII concentrate a large increase in the levels of plasma VIIIC was detected with a disappearance half-life of 3.5 hours. A specific non-crossreacting immunoradiometric assay (IRMA) showed that plasma levels of porcine vWFAg did not rise significantly after the infusion. Despite this, human vWFAg levels were notably elevated at 1 hour (40 u/dl by Laurell) and 2 hours (30 u/dl by IRMA) post infusion. Similarly, ristocetin induced platelet aggregation and plasma RRCo levels showed significant elevations , 2 hours after the infusion. Factor VIII multimers assessed on plasma samples taken over a similar time period revealed the transient appearance of a normal compliment of human factor VIII multimeric forms 2 hours after the infusion of porcine factor VIII concentrate. This study indicates that the abnormal pattern of factor VIII multimeric bands present in inhibitor-related variant acquired von Willebrand's disease can be transiently normalised by infused porcine factor VIII concentrate. Whether this represents antibody displacement or de novo synthesis is yet to be determined.
Studies of the human factor VIII/von Willebrand factor protein. III. Qualitative defects in von Willebrand's disease.