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SUMMARY
This chapter describes the classification, pathophysiology, clinical evaluation, and management of quantitative and qualitative inherited platelet disorders. Whereas some platelet disorders only result in bleeding, others are part of a broader clinical syndrome. Even with signs of bleeding, there is a large variability among patients. Bleeding is principally evident by excessive hemorrhage at mucocutaneous sites, ecchymoses, petechiae, epistaxis, gingival hemorrhage, and menorrhagia. The hereditary platelet disorders can be classified according to the underlying genetic mutation and the role the corresponding protein has in megakaryocyte and platelet production (Figs. 119–1 and 119–2). Furthermore, recommendations on how and when to use genomic analyses and deep sequencing in the diagnosis of possibly novel pathways that result in inherited platelet disorders are provided.1,2
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Acronyms and Abbreviations
ADP, adenosine diphosphate; BLOC, biogenesis of lysosome-related organelles complex; BSS, Bernard-Soulier syndrome; βTG, β-thromboglobulin; cAMP, cyclic adenosine monophosphate; CAMT, Congenital amegakaryocytic thrombocytopenia;CRP, collagen-related peptide;FBC, Full blood count;GFI1b, growth factor independent 1B; GP, glycoprotein; GPS, gray platelet syndrome; GT, Glanzmann thrombasthenia; HLA, human leukocyte antigen; HPS, Hermansky-Pudlak syndrome; HTS, High-throughput sequencing; Ig, immunoglobulin; IP3, inositol 1,4,5-triphosphate;IPD, Inherited Platelet Disorders; ITG, Integrin; LAD, leukocyte adhesion deficiency; LRO, lysosome-related organelles; MK, Megakaryocyte; PAR, protease-activated receptor; PI, phosphoinositide;PF4, platelet factor 4; PKC, protein kinase C; PLA2alpha, phospholipase A2alphaPLC, phospholipase C; PT, Paris-Trousseau ;PT-VWD, Platelet-Type Von Willebrand Disease; rFVIIa, recombinant factor VIIa; SDS-PAGE, sodium dodecylsulfate polyacrylamide gel electrophoresis; TAR, Thrombocytopenia absent radius; THPO, receptor of thrombopoietin;TPO-RAS, thrombopoietin-receptor agonists;TGF, transforming growth factor; TXA2, thromboxane A2; VUS, Variant of Unknown Significance; VWD, von Willebrand disease; VWF, von Willebrand factor; WAS, Wiskott-Aldrich syndrome.
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