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SUMMARY
Thrombocytopenia is one of the most frequent causes for hematologic consultation in the practice of medicine, and may be life threatening. Although the normal platelet count in humans (150 to 400 × 109/L) far exceeds the minimal level required to avoid pathologic hemorrhage (<50 × 109/L), a number of medical conditions either increasing the destruction of platelets or reducing their production, enhance the risk of bleeding. This chapter discusses an approach to the diagnosis of thrombocytopenia, grouping various causes by mechanism of action, and describing our current understanding of the pathogenesis, treatment and prognosis. In the vast majority of patients, a cause for thrombocytopenia can be identified, and effective therapy instituted.
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Acronyms and Abbreviations
ACOG, American College of Obstetricians and Gynecologists; ADP, adenosine diphosphate; AFLP, acute fatty liver of pregnancy; AML, acute myelogenous leukemia; APLA, antiphospholipid antibody; APS, antiphospholipid syndrome; ARC, arthrogryposis–renal dysfunction–cholestasis; ASH, American Society of Hematology; ATG, antithymocyte globulin; ATRUS, amegakaryocytic thrombocytopenia with radioulnar synostosis; CAMT, congenital amegakaryocytic thrombocytopenia; CAPTURE, c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina; CTP, cyclic thrombocytopenia; CVID, common variable immunodeficiency; DIC, disseminated intravascular coagulation; EDTA, ethylenediaminetetraacetic acid; EPIC, Evaluation of 7E3 for the Prevention of Ischemic Complications; EPILOG, Evaluation of Percutaneous Transluminal Coronary Angioplasty to Improve Long-term Outcome of c7E3 GPIIb-IIIa Receptor Blockade; EPISTENT, Evaluation of Platelet IIb/IIIa Inhibitor for Stenting; Flt1, fms-like tyrosine kinase-1; FPD/AML, familial platelet disorder with propensity to acute myeloid malignancy; GP, glycoprotein; HCV, hepatitis C virus; HELLP, hemolysis, elevated liver enzymes, low platelets; HIT, heparin-induced thrombocytopenia; HUS, hemolytic uremic syndrome; HPA, human platelet alloantigen; ICSH, International Council for Standardization in Hematology; IDA, iron-deficiency anemia; IPD, inherited platelet disorder; ITP, immune thrombocytopenia; IVIG, intravenous immunoglobulin; IWG, International Working Group; LTA, light transmission aggregometry; MACE, modified antigen capture enzyme-linked ımmunosorbent assay; MAIPA, monoclonal antibody-specific immobilization of platelet antigens; MDS, myelodysplastic syndrome; MHC, major histocompatibility complex; NAIT, neonatal alloimmune thrombocytopenia; PAIgG, platelet-associated immunoglobulin G; sFlt1, soluble Flt1; SLE, systemic lupus erythematosus; TAR, thrombocytopenia with absent radii; TPO, thrombopoietin; Treg, T-regulatory; TTP, thrombotic thrombocytopenic purpura; VEGF, vascular endothelial growth factor; VWD, von Willebrand disease; VWF, von Willebrand factor.
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DEFINITION AND HISTORY
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Platelets are anucleate blood cells produced in the marrow by polyploid cells termed megakaryocytes and were described in the 19th century after the application of the improved compound microscope allowed these very small cellules, approximately 2 μM in diameter, to be identified. Many early investigators are associated with the discovery of blood platelets, including Donné, Hayem, Bizzozero, and Osler, but it was James Homer Wright who, in 1906, using his special stain (later called Wright stain), described the morphology of platelets with their central granular area and marginal hyaline zone and established that they were the product of the fragmentation of marrow megakaryocytes. Clot retraction was discovered long before platelets, but Hayem, through a series of studies, showed retraction to be dependent on platelets. During the mid-20th ...