Congenital defects in platelet function are associated with
bleeding manifestations of variable intensity and arise by diverse mechanisms. Defects in platelet-vessel wall interaction (disorders of adhesion) may arise because of qualitative or quantitative abnormalities in plasma
von Willebrand factor (
von Willebrand disease) or in
platelet glycoprotein Ib, the binding site on platelets for
von Willebrand factor (
Bernard-Soulier syndrome). Disorders characterized by abnormal platelet-platelet interaction (disorders of aggregation) arise because of absence of plasma
fibrinogen (
congenital afibrinogenemia) or because of qualitative or quantitative abnormalities in
platelet glycoprotein IIb-IIIa complex (Glanzmann's
thrombasthenia). Patients with abnormalities in platelet secretion and signal transduction are a heterogeneous group characterized by impaired aggregation responses and secretion of granule contents. A small proportion of these patients have deficiency of granule stores (
storage pool deficiency [SPD]) or impaired production of
thromboxane A2; in most, the mechanisms underlying the platelet dysfunction are unknown. Evidence is accumulating that at least some patients have abnormalities in early signal transduction events. Abnormalities in
phospholipase C activation,
G-protein activation, and other events (eg,
protein phosphorylation) have been documented. Platelets play a major role in blood coagulation, and in
Scott syndrome, there is an abnormality in platelet contribution to the mechanisms leading to
thrombin generation. In most patients with inherited platelet dysfunction, the underlying mechanisms remain to be delineated. Future studies of these patients should yield valuable new information on normal platelet mechanisms.