Red blood cell (RBC) transfusions are a critical component of patient care, with around 1.2 million units utilized annually in Canada alone. Patients with acute blood loss require temporary RBC transfusions until their erythropoiesis restores RBC levels. Those with chronic disorders, such as hemoglobinopathies and bone marrow cancers, rely on transfused RBCs for entire RBC circulatory lifespan. For these chronic recipients, selecting long-circulating RBC units could minimize transfusion-associated morbidity like iron overload and lung damage, yet established methods to identify these units are lacking.
This dissertation studied the potential to use RBC deformability as a surrogate marker for the transfused RBC circulatory clearance time. Deformability is vital for RBC function and has been considered a physical biomarker of circulation time in transfusion recipients. Our team has developed a unique microfluidic ratchet device to analyze RBC deformability. This device operates by directing individual RBCs to deform through a series of micrometer-scale constrictions much smaller than RBC diameter. A consistent force gradient is applied to each cell as it deforms through constrictions, enabling measurement of RBC deformability with high sensitivity and repeatability.
Using the microfluidic ratchet device, we show that RBC deformability varies across healthy donors, but is consistent for each donor over multiple donations. Furthermore, RBC deformability is preserved during the standard 42-day cold storage in blood bags but degrades significantly beyond this timeframe. Additionally, deformability can be estimated by sampling from the blood bag tubing segment instead of puncturing the bag. Finally, we use a mouse transfusion model to investigate whether low-deformability RBCs are preferentially cleared from circulation. We show the rigid fraction of transfused RBCs are rapidly cleared, while transfused RBCs remaining in circulation had a deformability profile closely matching that of endogenous RBCs from the recipient mouse.
Our findings provide strong evidence that RBC deformability, measured using the microfluidic ratchet device, may be used to predict RBC circulation time in transfusion recipients. If validated using future clinical studies, this approach could be used to identify donors who can provide long-circulating RBC units and reserve these units for chronic transfusion recipients to reduce transfusion frequency and associated morbidity.Medicine, Faculty ofPathology and Laboratory Medicine, Department ofGraduat
