Journal article

Effect of thrombopoietin receptor agonists on the apoptotic profile of platelets in patients with chronic immune thrombocytopenia

William Beau Mitchell, Mariana P Pinheiro, Nayla Boulad, David Kaplan, Michele N Edison, Bethan Psaila, Marissa Karpoff, Michael J White, Emma C Josefsson, Benjamin T Kile, James B Bussel

AMERICAN JOURNAL OF HEMATOLOGY | WILEY | Published : 2014

Abstract

Platelet survival depends upon mediators of apoptosis e.g., Bcl-xL, Bax, and Bak, which are regulated by thrombopoietin (TPO)-mediated AKT signaling. Thrombopoietin receptor (TPO-R) signaling might decrease platelet and/or megakaryocyte apoptosis and increase the platelet count. This study therefore explored anti-apoptotic effects of TPO-R-agonists in vivo on platelets of patients with immune thrombocytopenia. Patients received eltrombopag or romiplostim for two weeks. Total, immature, and large platelet counts were assessed as were Bcl-xL inhibitor assay; Bcl-xL Western blot; and flow cytometric (FACS) analysis of the AKT-signaling pathway. Eight/ten patients had platelet responses to eltro..

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University of Melbourne Researchers

Grants

Awarded by Academy of Medical Sciences (AMS)


Awarded by National Institute for Health Research


Funding Acknowledgements

JBB has received research funding from Amgen and Glaxo Smith Kline.