MEGAKARYOCYTES AND PLATELETS IN ALPHA-GRANULE DISORDERS

This chapter summarizes research data contributing to current understa nding of disorders affecting alpha-granules of megakaryocytes and plat elets. Diagnostic features of the gray platelet syndrome are well defi ned. Combined evidence suggests a defect, specific to the megakaryocyt e cell lineage, causing a cytoskeletal abnormality and defective targe ting of endogenously synthesized proteins to the alpha-granule. The ab normalities linked by signal transduction pathways. von Willebrand dis ease and afibrinogenaemia are disorders which highlight the functional importance of platelet storage pools of von Willebrand factor and fib rinogen, essential ligands in the process of adhesion and aggregation. The abnormality in the factor V Quebec disorder leads to a degradatio n of most proteins contained within the a-granule. The familial platel et disorder Paris-Trousseau thrombocytopenia is the only alpha-granule disorder associated with a cytogenetic abnormality, and it presents a useful model for exploring the genetic influence on regulation of thr ombopoiesis. Study of these syndromes has elucidated aspects of the ph ysiology of normal megakaryocyte maturation and platelet formation, in cluding storage organelle biosynthesis.