Singhal, R. and Annarapu, G. K. and Pandey, A. and Chawla, S. and Ojha, A. and Gupta, A. and Cruz, M. A. and Seth, T. and Guchhait, P. (2015) Hemoglobin interaction with GP1b induces platelet activation and apoptosis: a novel mechanism associated with intravascular hemolysis. Haematologica, 100 (12). pp. 1526-1533. ISSN 0390-6078

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Abstract

Intravascular hemolysis increases the risk of hypercoagulation and thrombosis in hemolytic disorders. Our study shows a novel mechanism by which extracellular hemoglobin directly affects platelet activation. The binding of Hb to glycoprotein1bα activates platelets. Lower concentrations of Hb (0.37-3 μM) significantly increase the phosphorylation of signaling adapter proteins, such as Lyn, PI3K, AKT, and ERK, and promote platelet aggregation in vitro. Higher concentrations of Hb (3-6 μM) activate the pro-apoptotic proteins Bak, Bax, cytochrome c, caspase-9 and caspase-3, and increase platelet clot formation. Increased plasma Hb activates platelets and promotes their apoptosis, and plays a crucial role in the pathogenesis of aggregation and development of the procoagulant state in hemolytic disorders. Furthermore, we show that in patients with paroxysmal nocturnal hemoglobinuria, a chronic hemolytic disease characterized by recurrent events of intravascular thrombosis and thromboembolism, it is the elevated plasma Hb or platelet surface bound Hb that positively correlates with platelet activation.

Item Type:	Article
Subjects:	Biomedical Science Biochemical and Biophysical Sciences
Depositing User:	RCB Library
Date Deposited:	07 Nov 2017 13:00
Last Modified:	07 Nov 2017 13:00
URI:	http://rcb.sciencecentral.in/id/eprint/116

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