Increased Fibrinogen Binding to Platelets from Patients with Familial Hypercholesterolemia

Familial hypercholesterolemia (FH) is a disease marked by a high incidence of thrombotic episodes and hypersensitivity of the patients ' platelets to naturally occur-ring aggregating agents. Prostaglandin/thromboxane (PG/Tx) formation, adenosine 5-diphosphate (ADP) secretion, and fibrinogen binding to platelets are all believed to be involved in the mechanisms of platelet aggregation. Therefore, we studied the interrelated roles of these processes in the platelets of nine FH patients and 10 controls. In response to ADP, collagen, or thrombin, FH platelets bound about twice as much 12Sl-fibrinogen as controls. This ratio did not change after suppression of PG/Tx formation by aspirin. With or without aspirin, FH platelets always aggregated in response to significantly lower concentrations of these agents than did platelets from normal controls. After stimulation with thrombin or collagen, the hyperaggregable platelets from FH patients were shown to bind significantly more fibrinogen than control platelets even when PG/Tx formation was suppressed (aspirin) and secreted ADP was scavenged (apyrase). To determine whether the increased fibrinogen bind-ing observed in FH platelets is due to a qualitative or quantitative abnormality of th