CONGENITAL DISORDERS OF PLATELET-FUNCTION - DISORDERS OF SIGNAL-TRANSDUCTION AND SECRETION

Congenital defects in platelet function are associated with bleeding m anifestations of variable intensity and al ise by diverse mechanisms. Defects in platelet-vessel wall interaction (disorders of adhesion) ma y arise because of qualitative or quantitative abnormalities in plasma von Willebrand factor (von Willebrand disease) or in platelet glycopr otein Ib, the binding site on platelets for von Willebrand factor (Ber nard-Soulier syndrome). Disorders characterized by abnormal platelet-p latelet interaction (disorders of aggregation) arise because of absenc e of plasma fibrinogen (congenital afibrinogenemia) or because of qual itative or quantitative abnormalities in platelet glycoprotein IIb-III a 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 granu le contents, A small proportion of these patients have deficiency of g ranule stores (storage pool deficiency [SPD]) or impaired production o f thromboxane A(2); in most, the mechanisms underlying the platelet dy sfunction are unknown. Evidence is accumulating that at least some pat ients have abnormalities in early signal transduction events, Abnormal ities in phospholipase C activation, G-protein activation, and other e vents (eg, protein phosphorylation) have been documented. Platelets pl ay a major role in blood coagulation, and in Scott syndrome, there is an abnormality in platelet contribution to the mechanisms leading to t hrombin generation. In most patients with inherited platelet dysfuncti on, the underlying mechanisms remain to be delineated. Future studies of these patients should yield valuable new information on normal plat elet mechanisms.