The red blood cell death receptor and thrombosis
Nigel Mackman
Nigel Mackman
Published August 13, 2018
Citation Information: J Clin Invest. 2018;128(9):3747-3749. https://doi.org/10.1172/JCI122881.
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The red blood cell death receptor and thrombosis

Abstract

RBCs are the most abundant circulating cells in humans and typically comprise 35% to 45% of the blood volume (hematocrit). Anemia is associated with an increase in bleeding, and epidemiological studies have shown an association between an elevated hematocrit and thrombosis. RBCs may contribute to hemostasis and thrombosis via mechanisms that include platelet margination leading to an increase in the near-wall platelet concentration, blood viscosity, thrombin generation, and platelet activation. In this issue of the JCI, Klatt et al. report that binding of the Fas ligand FasL on the surface of platelets to its cognate receptor FasR on the surface of RBCs increases thrombin generation in vitro and thrombosis in mouse models. This represents a new mechanism by which RBCs contribute to thrombosis.

Authors

Nigel Mackman

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Figure 1

Composition of hemostatic plugs and arterial and venous thrombi.

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Composition of hemostatic plugs and arterial and venous thrombi. (A) Hem...
(A) Hemostatic plugs consist of a core of highly activated platelets surrounded by fibrin and a shell of less activated platelets. RBCs force the smaller platelets to the vessel wall where they can monitor vascular integrity. (B) Arterial thrombi are platelet rich with few RBCs. In the ferric chloride model of carotid artery thrombosis the first event is binding of RBCs to the endothelium and subsequent recruitment of platelets followed by formation of large platelet aggregates. Platelet-RBC interactions mediated by FasL-FasR may contribute to thrombosis in the mouse ferric chloride model. (C) Venous thrombi contain red regions composed of RBCs and fibrin and white regions composed of platelets. Platelet-RBC interactions via FasL-FasR may enhance thrombosis in the mouse inferior vena cava model.