Congenital Vascular Defect Associated with Platelet Abnormality and Antihemophilic Factor Deficiency

Abstract

1. A kindred of 311 individuals, many members of which are affected by a hemorrhagic diathesis, has been described. 2. The variability in the manifestations of this diathesis is extreme. In its fullest expression the disease is characterized by a prolonged bleeding time with evidence of a morphologic defect in the platelets, and a deficiency in antihemophilic globulin. Some possibly affected individuals exhibit only a prolonged bleeding time, while, on the other hand, the clinically most severely affected individual, with AHF levels on several occasions of 5 to 10 per cent, has not been observed by us to have a prolonged bleeding time, although his platelets are morphologically abnormal. 3. Genetic analysis suggests that the hemorrhagic tendency is determined by a single dominant gene of variable penetrance and expressivity. 4. No satisfactory explanation can be developed on the basis of these studies for the association between platelet abnormality and AHF deficiency. More specifically, it is impossible to conclude whether the platelet defect is precursor to the AHF deficiency, or whether—as on a priori grounds seems less likely—this is an example of true genetic pleiotropy. 5. The terminologic chaos which afflicts the literature on hemorrhagic diatheses characterized by a prolonged bleeding time is discussed in the light of the findings in this one large kindred, and suggestions are advanced for minimizing confusion based on terminology alone.