Microparticles from stored red blood cells promote a hypercoagulable state in a murine model of transfusion

摘要

BackgroundRed blood cell-derived microparticles are biologically active, submicron vesicles shed by erythrocytes during storage. Recent clinical studies have linked the duration of red blood cell storage with thromboembolic events in critically ill transfusion recipients. In the present study, we hypothesized that microparticles from aged packed red blood cell units promote a hypercoagulable state in a murine model of transfusion. MethodsMicroparticles were isolated from aged, murine packed red blood cell units via serial centrifugation. Healthy male C57BL/6 mice were transfused with microparticles or an equivalent volume of vehicle, and whole blood was harvested for analysis via rotational thromboelastometry. Serum was harvested from a separate set of mice after microparticles or saline injection, and analyzed for fibrinogen levels. Red blood cell-derived microparticles were analyzed for their ability to convert prothrombin to thrombin. Finally, mice were transfused with either red blood cell microparticles or saline vehicle, and a tail bleeding time assay was performed after an equilibration period of 2, 6, 12, or 24 hours. ResultsMice injected with red blood cell-derived microparticles demonstrated an accelerated clot formation time (109.3?±?26.9 vs 141.6?±?28.2?sec) and increased α angle (68.8?±?5.0 degrees vs 62.8?±?4.7 degrees) compared with control (eachP?