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

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.

• Authors: Rashi Singhal, Gowtham K Annarapu, Ankita Pandey, Sheetal Chawla, Amrita Ojha, Avinash Gupta, Miguel A Cruz, Tulika Seth, Prasenjit Guchhait
• Journal: Haematologica (Haematologica) Vol. 100 Issue 12 Pg. 1526-33 (Dec 2015) ISSN: 1592-8721 [Electronic] Italy
• PMID: 26341739 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© Ferrata Storti Foundation.

Chemical References

• Hemoglobins
• Platelet Glycoprotein GPIb-IX Complex
• adhesion receptor

Topics

• Apoptosis
• Blood Platelets (metabolism, pathology)
• Female
• Hemoglobins (metabolism)
• Hemoglobinuria, Paroxysmal (pathology)
• Hemolysis
• Humans
• Male
• Platelet Activation
• Platelet Glycoprotein GPIb-IX Complex (metabolism)