Is It Possible to Reverse the Storage-Induced Lesion of Red Blood Cells?

Cold-storage of packed red blood cells (PRBCs) in the blood bank is reportedly associated with alteration in a wide range of RBC features, which change cell storage each on its own timescale. Thus, some of the changes take place at an early stage of storage (during the first 7 days), while others occur later. We still do not have a clear understanding what happens to the damaged PRBC following their transfusion. We know that some portion (from a few to 10%) of transfused cells with a high degree of damage are removed from the bloodstream immediately or in the first hour(s) after the transfusion. The remaining cells partially restore their functionality and remain in the recipient’s blood for a longer time. Thus, the ability of transfused cells to recover is a significant factor in PRBC transfusion effectiveness. In the present review, we discuss publications that examined RBC lesions induced by the cold storage, aiming to offer a better understanding of the time frame in which these lesions occur, with particular emphasis on the question of their reversibility. We argue that transfused RBCs are capable (in a matter of a few hours) of restoring their pre-storage levels of ATP and 2,3-DPG, with subsequent restoration of cell functionality, especially of those properties having a more pronounced ATP-dependence. The extent of reversal is inversely proportional to the extent of damage, and some of the changes cannot be reversed

Hemodynamic Functionality of Transfused Red Blood Cells in the Microcirculation of Blood Recipients

The primary goal of red blood cell (RBC) transfusion is to supply oxygen to tissues and organs. However, due to a growing number of studies that have reported negative transfusion outcomes, including reduced blood perfusion, there is rising concern about the risks in blood transfusion. RBC are characterized by unique flow-affecting properties, specifically adherence to blood vessel wall endothelium, cell deformability, and self-aggregability, which define their hemodynamic functionality (HF), namely their potential to affect blood circulation. The role of the HF of RBC in blood circulation, particularly the microcirculation, has been documented in numerous studies with animal models. These studies indicate that the HF of transfused RBC (TRBC) plays an important role in the transfusion outcome. However, studies with animal models must be interpreted with reservations, as animal physiology may not reflect human physiology. To test this concept in humans, we have directly examined the effect of the HF of TRBC, as expressed by their deformability and adherence to vascular endothelium, on the transfusion-induced effect on the skin blood flow and hemoglobin increment in β-thalassemia major patients. The results demonstrated, for the first time in humans, that the TRBC HF is a potent effector of the transfusion outcome, expressed by the transfusion-induced increase in the recipients' hemoglobin level, and the change in the skin blood flow, indicating a link between the microcirculation and the survival of TRBC in the recipients' vascular system. The implication of these findings for blood transfusion practice and to vascular function in blood recipients is discussed

Double-Facet Effect of Artificial Mechanical Stress on Red Blood Cell Deformability: Implications for Blood Salvage

The use of intra-operative blood salvage, dialysis, and artificial organs are associated with the application of non-physiological mechanical stress on red blood cells (RBCs). To explore the effect of these procedures on red cell deformability, we determined it before and after the mechanical stress application both in an in vitro system and following a blood-saving procedure. RBC from eight healthy donors and fifteen packed RBC units were subjected to mechanical stress. RBCs from five patients undergoing orthopedic surgery were also collected. We measured the percent of undeformable cells (%UDFC) in the red cell samples using our cell flow properties image analyzer, which provides the distribution of RBC deformability in a large cell population. Mechanical stress systematically reduced the cell deformability and increased the %UDFC, while simultaneously causing hemolysis of rigid, undeformable RBCs. Ultimately, the overall result depended on the initial level of the undeformable cells; the stress-induced change in the proportion of rigid cells (Δ%UDFC) increased (Δ%UDFC > 0) when its initial value was low, and decreased (Δ%UDFC < 0) when its initial value was high. This suggests that the final impact of mechanical stress on the percent of rigid cells in the RBC population is primarily determined by their initial concentration in the sample

Do We Store Packed Red Blood Cells under “Quasi-Diabetic” Conditions?

Red blood cell (RBC) transfusion is one of the most common therapeutic procedures in modern medicine. Although frequently lifesaving, it often has deleterious side effects. RBC quality is one of the critical factors for transfusion efficacy and safety. The role of various factors in the cells’ ability to maintain their functionality during storage is widely discussed in professional literature. Thus, the extra- and intracellular factors inducing an accelerated RBC aging need to be identified and therapeutically modified. Despite the extensively studied in vivo effect of chronic hyperglycemia on RBC hemodynamic and metabolic properties, as well as on their lifespan, only limited attention has been directed at the high sugar concentration in RBCs storage media, a possible cause of damage to red blood cells. This mini-review aims to compare the biophysical and biochemical changes observed in the red blood cells during cold storage and in patients with non-insulin-dependent diabetes mellitus (NIDDM). Given the well-described corresponding RBC alterations in NIDDM and during cold storage, we may regard the stored (especially long-stored) RBCs as “quasi-diabetic”. Keeping in mind that these RBC modifications may be crucial for the initial steps of microvascular pathogenesis, suitable preventive care for the transfused patients should be considered. We hope that our hypothesis will stimulate targeted experimental research to establish a relationship between a high sugar concentration in a storage medium and a deterioration in cells’ functional properties during storage

Red Blood Cell Deformability Is Expressed by a Set of Interrelated Membrane Proteins

Red blood cell (RBC) deformability, expressing their ability to change their shape, allows them to minimize their resistance to flow and optimize oxygen delivery to the tissues. RBC with reduced deformability may lead to increased vascular resistance, capillary occlusion, and impaired perfusion and oxygen delivery. A reduction in deformability, as occurs during RBC physiological aging and under blood storage, is implicated in the pathophysiology of diverse conditions with circulatory disorders and anemias. The change in RBC deformability is associated with metabolic and structural alterations, mostly uncharacterized. To bridge this gap, we analyzed the membrane protein levels, using mass spectroscopy, of RBC with varying deformability determined by image analysis. In total, 752 membrane proteins were identified. However, deformability was positively correlated with the level of only fourteen proteins, with a highly significant inter-correlation between them. These proteins are involved in membrane rafting and/or the membrane–cytoskeleton linkage. These findings suggest that the reduction of deformability is a programmed (not arbitrary) process of remodeling and shedding of membrane fragments, possibly mirroring the formation of extracellular vesicles. The highly significant inter-correlation between the deformability-expressing proteins infers that the cell deformability can be assessed by determining the level of a few, possibly one, of them

Successful management of an Iatrogenic portal vein and hepatic artery injury in a 4-month-old female patient: A case report and literature review

Serious iatrogenic vascular injuries are considered uncommon; however, they are underreported. There are limited studies discussing the proper management of these injuries; therefore, the management is often anecdotal. A 4-month-old female patient presented with elevated liver enzymes and cholecystitis with sludge. Her HIDA scan suggested biliary atresia. During the surgery, there was a bilateral iatrogenic injury to the hepato-duodenal ligament, including the portal vein, hepatic artery, and bile ducts. The patient underwent splenectomy and cholecystectomy, and the hepatic artery transection was successfully managed with a splenic artery jump graft and a portal vein bypass initiated with the SMV using a Gore-TexⓇ vascular graft. The management of iatrogenic vascular injury depends primarily on the assessment of the stage of the injury, which should be conducted by experienced surgeons using proper strategies in an established hepato-biliary surgical center. Additionally, there is little data provided in the literature, mostly case reports. Therefore, no preferred or specific approach can be found