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  • Title: 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.
    Author: Weiss HJ, Sussman II, Hoyer LW.
    Journal: J Clin Invest; 1977 Aug; 60(2):390-404. PubMed ID: 17621.
    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 approximately 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 degrees 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) approximately 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 approximately 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.
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