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Update on the causes of platelet disorders and functional consequences
Author(s) -
Freson K.,
Wijgaerts A.,
van Geet C.
Publication year - 2014
Publication title -
international journal of laboratory hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.705
H-Index - 55
eISSN - 1751-553X
pISSN - 1751-5521
DOI - 10.1111/ijlh.12213
Subject(s) - megakaryocyte , platelet , platelet disorder , hemostasis , blood platelet disorders , biology , platelet activation , gene , medicine , bioinformatics , microbiology and biotechnology , pathology , immunology , genetics , haematopoiesis , platelet aggregation , stem cell
Summary Platelets are derived from megakaryocytes in the bone marrow that create the cellular machinery the platelet needs to participate in the different processes of primary hemostasis including adhesion, activation and clot formation at the site of injury. Defects related to megakaryocyte differentiation, platelet formation, and/or platelet function can result in bleeding. Patients with thrombopathies can present with mucous membrane bleeding but may also present with bleeding following trauma or surgery. In this review, we have classified inherited platelet bleeding disorders ( IPD ) according to their underlying defective pathway: transcription regulation, TPO signaling, cytoskeletal organization, apoptosis, granule trafficking, and receptor signaling. Platelet function testing has provided insights into the underlying molecular defects that can result in bleeding. A major step forward was made during the last 3 years using new‐generation genetic approaches that resulted in the discovery of novel genes such as NBEAL 2, RBM 8A, ACTN 1, and GFI 1B for the well‐known IPD that cause gray platelet syndrome, thrombocytopenia‐absent radius syndrome, and autosomal dominant thrombocytopenias, respectively. In the near future, it is expected that a similar approach will identify many novel genes that cause IPD of unknown etiology, which are common. The future challenge will be to use a functional, systems biology approach to study the genes mutated in IPD and determine their roles in megakaryocyte and platelet biology and pathology.