Role of red blood cells in clinically relevant bleeding tendencies and complications

The multiple roles of red blood cells (RBCs) are often neglected as contributors in hemostasis and thrombosis. Proactive opportunities to increase RBC numbers, either acutely or subacutely in the case of iron deficiency, are critical as RBCs are the cellular elements that initiate hemostasis together with platelets and stabilize fibrin and clot structure. RBCs also possess several functional properties to assist hemostasis: releasing platelet agonists, promoting shear force-induced von Willebrand factor unfolding, procoagulant capacity, and binding to fibrin. Additionally, blood clot contraction is important to compress RBCs to form a tightly packed array of polyhedrocytes, making an impermeable seal for hemostasis. All these functions are important for patients having intrinsically poor capacity to cease bleeds (ie, hemostatic disorders) but, conversely, can also play a role in thrombosis if these RBC-mediated reactions overshoot. One acquired example of bleeding with anemia is in patients treated with anticoagulants and/or antithrombotic medication because upon initiation of these drugs, baseline anemia doubles the risk of bleeding complications and mortality. Also, anemia is a risk factor for reoccurring gastrointestinal and urogenital bleeds, pregnancy, and delivery complications. This review summarizes the clinically relevant properties and profiles of RBCs at various steps of platelet adhesion, aggregation, thrombin generation, and fibrin formation, including both structural and functional elements. Regarding patient blood management guidelines, they support minimizing transfusions, but this approach does not deal with severe inherited and acquired bleeding disorders where a poor hemostatic propensity is exacerbated by limited RBC availability, for which future guidance will be needed.