Mechanical Blood Trauma in Circulatory-Assist Devices
4. Sublethal blood trauma
Chronic anemia in patients supported with circulatory assist devices has often been attributed to undetermined mechanisms, although today we reasonably suspect it results from accumulating sublethal damage to RBC resulting in a shortened RBC lifespan. Before the release of hemoglobin from leaking or fragmented RBCs, mechanical damage to RBCs begins through alterations in mechanical properties such as an increase in RBC aggregability and decrease in deformability. This concept of sublethal RBC trauma was first introduced by Pierre Galletti, who discovered anemia and reduced RBC life span in animals subjected to extracorporeal perfusion longer than 10 hours. Subsequent studies have confirmed that RBCs are significantly altered during prolonged exposure to shear stresses, much below any hemolytic threshold, and this ultimately leads to post-perfusion anemia caused by early removal of damaged RBCs from circulation. The experiments of Sandza et al., in which an isolated rabbit spleen was perfused by a mixture of radiolabeled sheared and unsheared autologous RBC, showed that the spleen could recognize and selectively remove RBCs exposed to shear stresses of 8–12 N/m2 for two hours. This suggested that some perceptible changes to the mechanical properties of the RBC had occurred. Sutera suggested that a leakage of ions and larger molecules such as ATP, ADP and 2–3 diphosphoglycerate (2–3 DPG) through micropores of 10–20 Å in stretched RBCs can occur much earlier than leakage of Hb molecules. In vitro studies by Alkhamis et al. demonstrated that RBCs released a significant fraction of their ADP (2% at a shear rate of 5680 s−1), which induced platelet aggregation. Shortened RBC lifespan due to accelerated splenic sequestration, along with a leakage of ions and ATP has been observed in blood exposed to an extracorporeal system for just a few hours.