title: Megakaryocytes and platelets in alpha-granule disorders.
abstract: This chapter summarizes research data contributing to current understanding of disorders affecting alpha-granules of megakaryocytes and platelets. Diagnostic features of the gray platelet syndrome are well defined. Combined evidence suggests a defect, specific to the megakaryocyte cell lineage, causing a cytoskeletal abnormality and defective targeting of endogenously synthesized proteins to the alpha-granule. The abnormalities linked by signal transduction pathways. von Willebrand disease and afibrinogenaemia are disorders which highlight the functional importance of platelet storage pools of von Willebrand factor and fibrinogen, essential ligands in the process of adhesion and aggregation. The abnormality in the factor V Quebec disorder leads to a degradation of most proteins contained within the alpha-granule. The familial platelet 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 thrombopoiesis. Study of these syndromes has elucidated aspects of the physiology of normal megakaryocyte maturation and platelet formation, including storage organelle biosynthesis.
authors.affiliation: Haemophilia Centre, St Thomas' Hospital, London, UK.
authors.forename: M P
authors.initials: MP
authors.lastname: Smith
authors.forename: E M
authors.initials: EM
authors.lastname: Cramer
authors.forename: G F
authors.initials: GF
authors.lastname: Savidge
mesh_terms: D000347:Afibrinogenemia / Q000473:pathology; D000818:Animals; D001791:Blood Platelet Disorders / Q000473:pathology*; D001792:Blood Platelets / Q000473:pathology*; D006801:Humans; D008533:Megakaryocytes / Q000473:pathology*; D010981:Platelet Storage Pool Deficiency / Q000473:pathology; D013577:Syndrome; D013915:Thrombasthenia / Q000473:pathology; D014842:von Willebrand Diseases / Q000473:pathology