Congenital Disorders of Platelet Function

Platelets play a major role in normal hemostasis and congenital defects in platelet function are associated with bleeding manifestations that are largely mucocutaneous in origin and markedly variable in severity. They arise by different mechanisms and may be classified as disorders of: (1) platelet-agonist interaction, (2) platelet-vessel wall interaction (vWD and Bernard-Soulier syndrome), (3) platelet-platelet interaction (congenital afibrinogenemia and Glanzmann's thrombasthenia), (4) platelet secretion, and (5) platelet-coagulant protein interaction. Excluding vWD, most congenital platelet dysfunctions currently fall in the category of platelet secretion defects. Some of these patients have storage pool deficiency or defects in thromboxane synthesis, but the majority have normal granule stores. The underlying mechanisms in this large, heterogeneous group of dysfunctions remain to be elucidated. Bleeding episodes of vWD are managed by the administration of DDAVP or cryoprecipitate. The major treatment modality in the management of bleeding episodes and surgical procedures in patients with congenital platelet defects is platelet transfusions. Evidence is becoming available that many of these patients may respond to intravenous infusion of DDAVP with a shortening of the bleeding time. The specific groups of patients who will respond, and the efficacy of DDAVP in clinical situations remains to be established.