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

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

doi:10.1172/JCI108788

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

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

Published August 1, 1977 - More info

View PDF

Abstract

In normal plasma, the ratio of the procoagulant activity of factor VIII (VIII_AHF) to that of the von Willebrand factor activity (ristocetin cofactor, VIII_VWF) or factor VIII antigen (VIII_AGN) is ∼1, but ratios > 1 (e.g., VIII_AHF > VIII_VWF or VIII_AGN) 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 VIII_AHF 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 VIII_AHF activity remained after incubation. VIII_AHF was labile (e.g., 35-55% residual activity) in the “late” posttransfusion plasmas (VIII_AHF ≫ VIII_VWF) of a patient with von Willebrand's disease, but not in the “early” posttransfusion plasmas (VIII_AHF ∼ VIII_VWF). VIII_AHF was also labile in the (base-line) plasmas of three patients with von Willebrand's disease in whom the ratios of VIII_AHF to VIII_VWF 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 VIII_AHF. In both of these patients, and in the late posttransfusion plasmas, labile VIII_AHF activity could be stabilized by the addition of purified von Willebrand factor (lacking VIII_AHF activity) or by hemophilic plasma, but not by plasmas of patients with severe von Willebrand's disease. Thus, VIII_VWF may serve to stabilize VIII_AHF and this might explain the posttransfusion findings in von Willebrand's disease.