title: Increased fibrinogen binding to platelets from patients with familial hypercholesterolemia.
abstract: Familial hypercholesterolemia (FH) is a disease marked by a high incidence of thrombotic episodes and hypersensitivity of the patients' platelets to naturally occurring 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 125I-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 binding observed in FH platelets is due to a qualitative or quantitative abnormality of the platelet receptor, we used a monoclonal antibody (B79.7) that is specific for the receptor. The amount of B79.7 that bound to platelets from control and FH subjects was similar. In addition (as in normal individuals), the antibody inhibited aggregation and fibrinogen binding of FH platelets.
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002648:Child; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood*; D008297:Male; D010974:Platelet Aggregation; D013931:Thromboxanes / Q000096:biosynthesis
chemical_list: D000906:Antibodies; D013931:Thromboxanes; D005340:Fibrinogen; D001241:Aspirin