Heterozygosity and Homozygosity in von Willebrand’s Disease : A Study of 108 Cases

Factor VIII/Willebrand Factor (F. VIII/WF) resides on a multimeric glycoprotein under autosomal control. Von Willebrand’s disease (vWd) may be related to a quantitative (inability to produce F. VIII/WF) or to a qualitative defect (production of an abnormal F. VIII/WF). The study of 108 cases illustrates the various genetic defects. In 33 cases from 21 families, the severity of the disease was consistent with a homozygous state. All showed a total lack of Factor VIII related antigen (VIIIR:AG) by immunoradiómetry, contrasting with low (1–5%) but detectable Factor VIII procoagulant activity (VIII:C). 4 of these patients developed antibodies which precipitated VIIIR:AG and neutralized Willebrand Factor activity (VIIIR:WF). In 16 of these 21 families, the parents were first cousins and 84% of the 48 relatives studied showed an abnormally high ratio of VIIIrC to VIIIR:WF -together with a qualitatively normal protein- consistent with a heterozygous state. A further 8 unrelated patients showed a less severe defect (5–20% of VIII:C, VIIIR:AG and VIIIR:WF) with a qualitatively normal protein. The remaining 19 patients had higher levels of VIIIR:AG than of VIIIR:WF and a qualitatively abnormal protein as demonstrated by electrophoretic mobility, agarose elution pattern, precipitation by concanavalin A and dose-response curve by immunoradiometry.

 

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