Inherited Platelet Disorders: Diagnosis and Management

Abstract

Inherited disorders of platelets are characterized by highly variable mucocutaneous bleeding manifestations and excessive hemorrhage following surgical procedures or trauma. They include patients who have decreased platelet counts, abnormal platelet function or a combination of both, in general reflecting underlying abnormalities that culminate in defective platelet production and function. Over the last two decades there has been an impressive increase in the number of genetic abnormalities identified as leading to inherited thrombocytopenias. In some of these patients platelets have impaired function as well. Most patients with inherited platelet function have mild to moderate bleeding manifestations. In the vast majority of patients suspected to have an inherited platelet function defect the molecular and genetic mechanisms are unknown. The platelet dysfunction in these patients arises by diverse mechanisms, including abnormalities in membrane glycoproteins, granules and their contents, platelet signaling and secretion mechanisms, thromboxane production pathways and in platelet procoagulant activities. The platelet dysfunction may arise due to mutation in a transcription factor (e.g. RUNX1) leading to abnormalities in multiple mechanisms involved in platelet production as well as in function. In this chapter, clinical and laboratory aspects of Inherited disorders of platelets are discussed.