Storage of packed red blood cells impairs an inherent coagulation property of erythrocytes

Abstract

Storage of packed red blood cells is associated with changes in erythrocytes that over time increasingly impair cellular function and potentially contribute to adverse effects associated with blood transfusion. Exposure of phosphatidylserine at the outer membrane leaflet of erythrocytes and shedding of microvesicles (MVs) during packed red blood cell storage are alterations assumed to increase the risk of prothrombotic events in recipients. Here, we used rotational thromboelastometry to study the coagulation process in blood samples with erythrocytes from stored PRBCs reconstituted with freshly prepared platelet-rich plasma. We explored the influence of following effects on the coagulation process: 1) PRBC storage duration, 2) differences between erythrocytes from stored PRBCs compared to freshly drawn erythrocytes, and 3) the contribution of added MVs. Interestingly, despite of a higher fraction of PS-positive cells, erythrocytes from PRBCs stored for 6 weeks revealed longer clotting times than samples with erythrocytes stored for 2 or 4 weeks. Further, clotting times and clot formation times were considerably increased in samples reconstituted with erythrocytes from stored PRBCs as compared to fresh erythrocytes. Moreover, MVs added to reconstituted samples elicited only comparably small and ambiguous effects on coagulation. Thus, this study provides no evidence for an amplified clotting process from prolonged storage of PRBCs but on the contrary implicates a loss of function, which may be of clinical significance in massive transfusion. Our observations add to the increasing body of evidence viewing erythrocytes as active players in the clotting process.

Erythrocyte Membrane Biophysical Changes Mediated by Pooled Immunoglobulin G and Hematin: Electrokinetic and Lipid Peroxidation Studies

“…Data about ∆Hemolysis (Hb-release) under biomacromolecule treatment were characterized by 30 min time periods of incubation in different concentrations of salt media according to the protocols described after the incubation of erythrocytes and biomacromolecules for 1 h at 37 °C, as well as after the preincubation of pooled immunoglobulin G and hematin in PBS, pH 7.4, for 1 h at 37 °C after gentle mixing. According to our results and the data of [ 35 ], no blood hemolysis was expected and observed up to one week after its storage before our measurements.…”

Red blood cell transfusion-related dynamics of extracellular vesicles in intensive care patients: a prospective subanalysis

“…Furthermore, the main study focused on the recruitment of ICU patients and the detection of eicosanoids in plasma. Therefore, other parameters of interest in plasma such as hemolysis parameters (e.g., free hemoglobin), pro- and anti-inflammatory cytokines, and coagulation parameters were not investigated 35 – 37 .…”

Red blood cell transfusion-related eicosanoid profiles in intensive care patients—A prospective, observational feasibility study

“…Furthermore, future studies may focus on non-direct mechanisms/pathways and negative feedback regulation via lipoxygenase and cytochrome P450 pathways ( Dennis and Norris, 2015 ) or T-cell regulation ( Nore et al 2020 ). In addition to eicosanoids, extracellular vesicles could act as possible mediators of TRIM ( Öhlinger et al 2022 ). In order to improve recruitment, follow-up studies should factor in 24/7 availability of qualified study staff.…”