Coagulation abnormalities of sickle cell disease: Relationship with clinical outcomes and the effect of disease modifying therapies

Noubouossié, Denis; Key, Nigel S.; Ataga, Kenneth I.

doi:10.1016/j.blre.2015.12.003

Cited by 108 publications

(106 citation statements)

References 195 publications

(233 reference statements)

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“…Some remarkable examples of phosphatidylserine exposure in RBC membranes are sickle cell disease and thalassemia [46, 47]. The abnormal phosphatidylserine exposure in sickle cell disease is thought to result from the repeated cell sickling and unsickling that are linked to polymerization and depolymerization of mutated hemoglobin [48].…”

Section: Phosphatidylserine Exposure In Rbc Membranementioning

confidence: 99%

Role of red blood cells in haemostasis and thrombosis

Litvinov

Weisel

2016

ISBT Science Series

155

154

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In contrast to an obsolete notion that erythrocytes, or red blood cells (RBCs), play a passive and minor role in hemostasis and thrombosis, over the past decades there has been increasing evidence that RBCs have biologically and clinically important functions in blood clotting and its disorders. This review summarizes the main mechanisms that underlie the involvement of RBCs in hemostasis and thrombosis in vivo, such as rheological effects on blood viscosity and platelet margination, aggregation and deformability of RBCs; direct adhesion and indirect biochemical interactions with endothelial cells and platelets, etc. The ability of stored and pathologically altered RBCs to generate thrombin through exposure of phosphatidylserine has been emphasized. The procoagulant and prothrombotic potential of RBC-derived microparticles transfused with stored RBCs or formed in various pathological conditions associated with hemolysis has been described along with prothrombotic effects of free hemoglobin and heme. Binding of fibrinogen or fibrin to RBCs may influence their effects on fibrin network structure, clot mechanical properties, and fibrinolytic resistance. Recent data on platelet-driven clot contraction show that RBCs compressed by platelets pulling on fibrin form a tightly packed array of polyhedral erythrocytes, or polyhedrocytes, which comprises a nearly impermeable barrier important for hemostasis and wound healing. RBCs may perform dual roles, both helping to stem bleeding but at the same time contributing to thrombosis in a variety of ways.

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Section: Phosphatidylserine Exposure In Rbc Membranementioning

confidence: 99%

Role of red blood cells in haemostasis and thrombosis

Litvinov

Weisel

2016

ISBT Science Series

155

154

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“…Pro [18][19][20][21][22][23][24][25] RBCs release membrane-derived procoagulant microvesicles bearing phosphatidylserine during in vivo aging and in vitro storage Pro [28][29][30][31]33,34] Meizothrombin, a protein C activator with low fibrinogen-cleaving activity, is formed on RBCs and released into the blood Anti [20] Factor IX is activated directly by an elastase-like enzyme on the RBC Pro [31,32,34,36,37,[40][41][42][43][44][45][47][48][49] Quantitative and qualitative changes in RBCs related to bleeding and thrombosis…”

Section: Introductionmentioning

confidence: 99%

Red blood cells: the forgotten player in hemostasis and thrombosis

Weisel

Litvinov

2019

Journal of Thrombosis and Haemostasis

308

272

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Summary New evidence has stirred up a long‐standing but undeservedly forgotten interest in the role of erythrocytes, or red blood cells (RBCs), in blood clotting and its disorders. This review summarizes the most recent research that describes the involvement of RBCs in hemostasis and thrombosis. There are both quantitative and qualitative changes in RBCs that affect bleeding and thrombosis, as well as interactions of RBCs with cellular and molecular components of the hemostatic system. The changes in RBCs that affect hemostasis and thrombosis include RBC counts or hematocrit (modulating blood rheology through viscosity) and qualitative changes, such as deformability, aggregation, expression of adhesive proteins and phosphatidylserine, release of extracellular microvesicles, and hemolysis. The pathogenic mechanisms implicated in thrombotic and hemorrhagic risk include variable adherence of RBCs to the vessel wall, which depends on the functional state of RBCs and/or endothelium, modulation of platelet reactivity and platelet margination, alterations of fibrin structure and reduced susceptibility to fibrinolysis, modulation of nitric oxide availability, and the levels of von Willebrand factor and factor VIII in blood related to the ABO blood group system. RBCs are involved in platelet‐driven contraction of clots and thrombi that results in formation of a tightly packed array of polyhedral erythrocytes, or polyhedrocytes, which comprises a nearly impermeable barrier that is important for hemostasis and wound healing. The revisited notion of the importance of RBCs is largely based on clinical and experimental associations between RBCs and thrombosis or bleeding, implying that RBCs are a prospective therapeutic target in hemostatic and thrombotic disorders.

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“…[6][7][8][9] Sickle cell-specific risk factors include platelet activation, chronic activation of coagulation secondary to externalization of the highly procoagulant phosphatidylserine on the sickled red blood cells, increased expression of tissue factor on circulating monocytes, and acquired deficiency of natural anticoagulants (proteins S and C). [10][11][12][13][14][15] Previously, we reported a single-institution retrospective study of 414 pediatric patients (#21 years) with SCD followed at Nationwide Children's Hospital between 2009 and 2015. 16 Cumulative incidence of VTE was found to be 2.9% (12/414).…”

Section: Introductionmentioning

confidence: 99%