Red blood cells with reduced deformability are selectively cleared from circulation in a mouse model

Donated red blood cells (RBCs) collected for blood transfusions progressively lose their deformability due to natural aging and cold storage in blood bags. This loss accelerates circulatory clearance via mechanical sensing by the spleen, leading to RBC retention and entrapment. Although reduced deformability is known to shorten RBC circulation time, the extent to which splenic clearance distinguishes and removes RBCs with altered deformability is poorly understood. Here, we show that subpopulations of donor RBCs with a deformability distribution distinct from endogenous recipient's RBCs are selectively and specifically cleared from circulation within 24 hours of infusion in a mouse model, whereas donor RBCs with a deformability distribution similar to endogenous recipient RBCs persist and undergo normal clearance. We performed this study by treating murine donor RBCs with the mild catalase inhibitor aminotriazole to generate donor RBCs with a widened range of deformability. These cells were then fluorescently labeled and infused into syngeneic recipients. Using a microfluidic device capable of deformability-based sorting of RBCs, we concurrently measured the deformability distribution of donor RBCs pretransfusion and posttransfusion, along with endogenous recipient RBCs. Our findings provide direct evidence that RBCs with deformability profiles distinct from endogenous recipient RBCs are selectively and specifically cleared from circulation.