Survival of red blood cells after transfusion: processes and consequences

Abstract

The currently available data suggest that efforts toward improving the quality of red blood cell (RBC) blood bank products should concentrate on: (1) preventing the removal of a considerable fraction of the transfused RBCs that takes place within the first hours after transfusion; (2) minimizing the interaction of the transfused RBCs with the patient's immune system. These issues are important in reducing the number and extent of the damaging side effects of transfusions, such as generation of alloantibodies and autoantibodies and iron accumulation, especially in transfusion-dependent patients. Thus, it becomes important for blood bank research not only to assess the classical RBC parameters for quality control during storage, but even more so to identify the parameters that predict RBC survival, function and behavior in the patient after transfusion. These parameters are likely to result from elucidation of the mechanisms that underly physiological RBC aging in vivo, and that lead to the generation of senescent cell antigens and the accumulation of damaged molecules in vesicles. Also, study of RBC pathology-related mechanisms, such as encountered in various hemoglobinopathies and membranopathies, may help to elucidate the mechanisms underlying a storage-associated increase in susceptibility to physiological stress conditions. Recent data indicate that a combination of new approaches in vitro to mimick RBC behavior in vivo, the growing knowledge of the signaling networks that regulate RBC structure and function, and the rapidly expanding set of proteomic and metabolomic data, will be instrumental to identify the storage-associated processes that control RBC survival after transfusion.

Propensity of red blood cells to undergo P2X7 receptor–mediated phosphatidylserine exposure does not alter during in vivo or ex vivo aging

“…Given that this process does not increase during RBC aging (this study) and that direct evidence for PS exposure in the removal of senescent RBCs is lacking, 1 it appears unlikely that P2X7--mediated PS exposure plays a major role in the removal of healthy, senescent RBCs. Rather it remains possible that ATP--induced PS exposure may act as a marker of recent P2X7 activation and that some other P2X7--mediated event, such as the ATP--induced release of epoxyeicosatrienoic acids (as observed with rat RBCs), 41 is the main physiological role of P2X7 activation in human RBCs.…”

“…1 These changes include increased exposure of phosphatidylserine (PS) on the RBC plasma membrane, 2 which parallels changes in RBCs aging in vivo. 3 Collectively, these and other studies support the concept that RBCs continue to age during ex vivo storage.…”

Biophysical and Biochemical Markers of Red Blood Cell Fragility

“…The aging-produced 'senescent' cells are characterized by the loss of cell surface area and cell morphology alterations [7], resulting from the shedding of hemoglobin(Hb)-containing vesicles [3,6,8,9]. The cold storage of packed RBCs (PRBCs) is associated with a continuous increase in the percentage of cells with impaired functionality [10][11][12]. This included increased cell rigidity (reduced deformability) and aggregability [12][13][14], reduced level of cell membrane stomatin [15], and translocation of phosphatidylserine (PS) to the cell surface [9,16], all leading to an increased adherence to endothelial cells [14].…”

Natural Antioxidants Improve Red Blood Cell “Survival” in Non-Leukoreduced Blood Samples

“…The levels malondialdehyde (MDA), ascorbate (ASC), dehydroascorbic acid (DHA), interleukin-6 (IL-6) were shown to increase significantly during the storage period [9,10] suggesting a progressive oxidative stress in preserved cells. It causes disruption of the cytoskeleton, aggregation of band 3 and release of vesicles [5,6,7,11,12]. At the same time, lipid peroxidation facilitates formation of advanced glycation end products (AGEs).…”