Stabilization of Factor VIII in Plasma by the von Willebrand Factor: STUDIES ON POSTTRANSFUSION AND DISSOCIATED FACTOR VIII AND IN PATIENTS WITH VON WILLEBRAND'S DISEASE

• Text
• PDF

Abstract

In normal plasma, the ratio of the procoagulant activity of factor VIII (VIIIAHF) to that of the von Willebrand factor activity (ristocetin cofactor, VIIIVWF) or factor VIII antigen (VIIIAGN) is ∼1, but ratios > 1 (e.g., VIIIAHF > VIIIVWF or VIIIAGN) may be observed in some patients with von Willebrand's disease and in the “late” posttransfusion plasmas of patients with this disorder. The lability of VIIIAHF was studied by incubating plasma, diluted 1:10 in imidazole buffer pH 7.1, for 6 h at 37°C. With normal plasmas, 77±12% (SD) of the original VIIIAHF activity remained after incubation. VIIIAHF was labile (e.g., 35-55% residual activity) in the “late” posttransfusion plasmas (VIIIAHF ≫ VIIIVWF) of a patient with von Willebrand's disease, but not in the “early” posttransfusion plasmas (VIIIAHF ∼ VIIIVWF). VIIIAHF was also labile in the (base-line) plasmas of three patients with von Willebrand's disease in whom the ratios of VIIIAHF to VIIIVWF were 4.4 to 8.1, but not in the plasmas of four other patients in whom the ratio was ∼ 1. The electrophoretic mobility of factor VIII antigen was increased in two of the three patients with labile VIIIAHF. In both of these patients, and in the late posttransfusion plasmas, labile VIIIAHF activity could be stabilized by the addition of purified von Willebrand factor (lacking VIIIAHF activity) or by hemophilic plasma, but not by plasmas of patients with severe von Willebrand's disease. Thus, VIIIVWF may serve to stabilize VIIIAHF and this might explain the posttransfusion findings in von Willebrand's disease.

Authors

Harvey J. Weiss, Ira I. Sussman, Leon W. Hoyer