Impaired proplatelet formation in immune thrombocytopenia: a novel mechanism contributing to decreased platelet count.

LEV PAOLA R; GRODZIELSKI MATÍAS; GOETTE NORA P; GLEMBOTSKY ANA C; ESPASANDIN YESICA R; PERDOMINICI M; CONTRUFO GERALDINE; MONTERO V; FERRARI LUCIANA; MOLINAS FELISA C; HELLER PAULA G; MARTA ROSANA F

BRITISH JOURNAL OF HAEMATOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2014 vol. 165 p. 854 - 864

0007-1048

Pathophysiological mechanisms contributing to 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. Patients 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 beta3 integrin phosphorylation. The presence of anti-GPIa-IIa auto-antibodies was associated with loss of normal inhibition of PPF induced by type I collagen, which could lead to premature platelet release in the osteoblastic niche. 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.