New emerging evidence is now prompting researchers to devote greater focus on the roles played by red blood cells (RBCs) in hemostasis. This short narrative review aims to outline the available research, past and current, that has revealed the role of RBCs in hemostasis, particularly blood clotting. Although early researchers suggested that RBCs were involved in blood clotting, they had insufficient evidence to support such claims. As a result, this area of research received little attention from other scientists. Early researchers primarily used quantitative measures of RBCs, namely hematocrit or RBC count, as higher numbers of RBCs modulate blood rheology by increasing viscosity. Recent research has instead shed light on the different measures of RBC function, such as expression of phosphatidylserine and adhesive proteins, aggregation, hemolysis, release of extracellular microvesicles, and erythrocyte volume. RBCs play a role in the contraction of clots by platelets, and the resulting densely packed array of polyhedral erythrocytes forms an almost impermeable barrier that is essential for hemostasis and wound healing. Renewed interest in RBCs is primarily due to the clinically and experimentally established relationships between erythrocytes and hemostasis, which have suggested that erythrocytes are potential targets for the treatment of hemostatic disturbances.
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