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Haematologica. 2015 Dec;100(12):1526-33. doi: 10.3324/haematol.2015.132183. Epub 2015 Sep 4.

Hemoglobin interaction with GP1bα induces platelet activation and apoptosis: a novel mechanism associated with intravascular hemolysis.

Author information

1
Disease Biology Laboratory, Regional Centre for Biotechnology, National Capital Region, Biotech Science Cluster, Faridabad, India Biotechnology Department, Manipal University, Manipal, Karnataka, India.
2
Disease Biology Laboratory, Regional Centre for Biotechnology, National Capital Region, Biotech Science Cluster, Faridabad, India.
3
Thrombosis Research Division, Baylor College of Medicine, Houston, TX, USA.
4
Hematology, All India Institute of Medical Sciences, New Delhi, India.
5
Disease Biology Laboratory, Regional Centre for Biotechnology, National Capital Region, Biotech Science Cluster, Faridabad, India prasenjit@rcb.res.in.

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.

PMID:
26341739
PMCID:
PMC4666328
DOI:
10.3324/haematol.2015.132183
[Indexed for MEDLINE]
Free PMC Article

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