Platelet Functional Abnormalities: A Report of Two Familial Defects in Interaction Between Collagen and Platelets and ADP Release

Two families have been studied, members of which have a lifelong hemorrhagic diathesis. In both families, a platelet functional abnormality has been found, with the coagulation mechanism intact. Findings common to both families were a prolonged bleeding time, reduced platelet adhesiveness, absence of the second wave of aggregation with ADP and reduced ADP release from platelets. The clot retraction, platelet factor 3 availability and aggregation of platelets with ADP in a final concentration of 1.0 and 20.0 µM were normal. The differences between the families were the platelet morphology, the in vitro adherence of platelets to collagen fibrils, the collagen-induced aggregation, and the thrombin-induced aggregation. In one of them, the Windle family, the platelets were abnormally large in size and showed a delayed adherence to collagen fibrils. The aggregation with collagen was either absent or feeble, and with thrombin, showed an abnormal pattern. In the other, the Hughes family, the platelets were morphologically normal and adhered to collagen fibrils normally. The aggregation with collagen initiated normally but usually did not proceed to completion and the aggregation with thrombin was normal. It appears that in the Windle family the main abnormality concerns the reaction between platelet and collagen and the condition is associated with impaired ADP-release mechanism and abnormal thrombin-platelet reaction, and in the Hughes family the ADP-release mechanism of platelets is defective. On the basis of current information, including that from these families, a classification of the various platelet functional abnormalities and methods for characterizing them is proposed.