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

Haematologica
Rashi SinghalPrasenjit Guchhait

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.

Citations

Apr 22, 2016·Platelets·Marion Lebois, Emma C Josefsson
Dec 10, 2016·PloS One·Gowtham K AnnarapuPrasenjit Guchhait
Feb 1, 2017·Scientific Reports·Amrita OjhaPrasenjit Guchhait
Apr 21, 2018·European Journal of Immunology·Rashi SinghalPrasenjit Guchhait
Mar 29, 2019·Annals of Biomedical Engineering·Kelli SimmsElaheh Rahbar
Jun 17, 2020·International Journal of Laboratory Hematology·Attaphon ChamchoiNathawut Sibmooh
Aug 2, 2017·Cancer Metastasis Reviews·Argentina OrnelasSteven Millward
Jun 19, 2020·International Journal of Molecular Sciences·Qinhong Wang, Rahima Zennadi
Apr 30, 2019·Journal of Immunology Research·Rashi SinghalPrasenjit Guchhait
Jun 16, 2018·Experimental and Therapeutic Medicine·Mingxia SunZhenyu Zhang
Jul 18, 2017·Biochemical and Biophysical Research Communications·Somanathapura K NaveenKumarKesturu S Girish
Apr 1, 2021·Free Radical Biology & Medicine·Ali MahdiJohn Pernow
Nov 4, 2020·Thrombosis Research·Kamila Czubak-ProwizorHalina Malgorzata Zbikowska
May 15, 2021·Blood Reviews·Laura Delvasto-NuñezSacha Zeerleder

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