Red Blood Cells with Reduced Deformability are Selectively Cleared from Circulation in a Mouse Model

• Sub-populations of donor red blood cells with low deformability are selectively cleared within 24 hours of transfusion in a murine model.

• Donor red blood cells that persist in circulation match the deformability distribution of endogenous red blood cells.

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. While 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 sub-populations 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 RBC 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 measure the deformability distribution of donor RBCs pre-transfusion and post-transfusion, 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.