Artículos de revistas
Impaired proplatelet formation in immune thrombocytopenia: a novel mechanism contributing to decreased platelet count
Fecha
2014-06Registro en:
Lev, Paola Roxana; Grodzielski, Matías; Goette, Nora Paula; Glembotsky, Ana Claudia; Espasandin, Yesica Romina; et al.; Impaired proplatelet formation in immune thrombocytopenia: a novel mechanism contributing to decreased platelet count; Wiley; British Journal of Haematology; 165; 6; 6-2014; 854-864
0007-1048
1365-2141
CONICET Digital
CONICET
Autor
Lev, Paola Roxana
Grodzielski, Matías
Goette, Nora Paula
Glembotsky, Ana Claudia
Espasandin, Yesica Romina
Pierdominici, Marta S.
Contrufo, Geraldine
Montero, Verónica S.
Ferrari, Luciana
Molinas, Felisa Concepción
Heller, Paula Graciela
Marta, Rosana Fernanda
Resumen
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-GPIIb-IIIa 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-IIa 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.