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Impaired proplatelet formation in immune thrombocytopenia: a novel mechanism contributing to decreased platelet count
Author(s) -
Lev Paola R.,
Grodzielski Matías,
Goette Nora P.,
Glembotsky Ana C.,
Espasandin Yesica R.,
Pierdominici Marta S.,
Contrufo Geraldine,
Montero Verónica S.,
Ferrari Luciana,
Molinas Felisa C.,
Heller Paula G.,
Marta Rosana F.
Publication year - 2014
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12832
Subject(s) - thrombopoiesis , platelet , megakaryocyte , chemistry , antibody , immune thrombocytopenia , immune system , medicine , endocrinology , immunology , microbiology and biotechnology , biology , haematopoiesis , stem cell
Summary The pathophysiological mechanisms contributing to the decreased platelet count in immune thrombocytopenia ( ITP ) are not entirely understood. Here, we investigated the key step of proplatelet formation ( PPF ) by studying the effect of ITP plasma in thrombopoiesis. Normal cord blood‐derived mature megakaryocytes were cultured in the presence of recalcified plasma from ITP patients, and PPF was evaluated by microscopic analysis. Patient samples induced a dose‐dependent inhibition in PPF , as well as decreased complexity of proplatelet architecture. Although slightly increased, plasma‐induced megakaryocyte apoptosis was not related to PPF impairment. Purified IgG reproduced the inhibitory effect, while platelet‐adsorbed plasma induced its reversion, suggesting the involvement of auto‐antibodies in the inhibition of thrombopoiesis. Impaired PPF , induced by ITP plasmas bearing anti‐ GPII b‐ III a antibodies, was related to their ability to interfere with the normal function of this integrin, as assessed by megakaryocyte PAC ‐1 binding and β3 integrin phosphorylation while the presence of anti‐glycoprotein Ia‐ II a auto‐antibodies was associated with loss of normal inhibition of PPF induced by type I collagen. In conclusion, abnormal thrombopoiesis comprising decreased PPF and morphological changes in proplatelet structure are induced by patient samples, unveiling new mechanisms contributing to decreased platelet count in ITP .