The involvement of cation leaks in the storage lesion of red blood cells

Abstract

Stored blood components are a critical life-saving tool provided to patients by health services worldwide. Red cells may be stored for up to 42 days, allowing for efficient blood bank inventory management, but with prolonged storage comes an unwanted side-effect known as the “storage lesion”, which has been implicated in poorer patient outcomes. This lesion is comprised of a number of processes that are inter-dependent. Metabolic changes include a reduction in glycolysis and ATP production after the first week of storage. This leads to an accumulation of lactate and drop in pH. Longer term damage may be done by the consequent reduction in anti-oxidant enzymes, which contributes to protein and lipid oxidation via reactive oxygen species. The oxidative damage to the cytoskeleton and membrane is involved in increased vesiculation and loss of cation gradients across the membrane. The irreversible damage caused by extensive membrane loss via vesiculation alongside dehydration is likely to result in immediate splenic sequestration of these dense, spherocytic cells. Although often overlooked in the literature, the loss of the cation gradient in stored cells will be considered in more depth in this review as well as the possible effects it may have on other elements of the storage lesion. It has now become clear that blood donors can exhibit quite large variations in the properties of their red cells, including microvesicle production and the rate of cation leak. The implications for the quality of stored red cells from such donors is discussed.

Consequences of Transfusing Blood Components in Patients With Trauma: A Conceptual Model

“…As the ATP-fueled sodiumpotassium pump within the cell membrane fails and results in accumulation of sodium within the cell, cellular swelling leads to a stiffened cellular structure and loss of the phospholipid membrane via formation of microvesicles or microparticles-small pieces of the cell membrane that encapsulate and remove intracellular components no longer essential to cellular function. 54,55 The combination of altered cellular chemistry and cellular structure results in decreased oxygenation ability, similar to the formation of spheroechinocytes.…”

“…The first type is necrotic cell death, which involves a breakdown in the cell membrane during storage similar to the breakdown that occurs in PRBCs, leading to leakage of the intracellular contents into the extracellular fluid. 54 The second type is a marked loss of platelets in vivo with reduction in ATP levels, with a maximum platelet survival of 9 to 10 days after transfusion before apoptotic cell death occurs. 62 No matter the cause or type of cell death during storage, the result is the same: a breakdown of the cell and activation of a procoagulant state.…”

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).…”

“…However, the use of hypothermia for cell storage is limited due to biological and biochemical alterations, known as storage lesions, that include changes in metabolism and cation gradients, oxidation, vesiculation, loss and cross-linking of band 3, carbonyl modification of band 4.1 [3,4], elevated PS exposure, reduced deformability and irreversible echinocytosis, hemolysis [5,6,7]. According to the current theory of storage lesion, the fall in ATP level weakens the cell antioxidant defence resulting in a decline in glutathione peroxidase activity [3,8] and cell damage by reactive oxygen species (ROS).…”

Regulation of red cell life-span, erythropoiesis, senescence and clearance

“…Blood storage damages RBCs facilitating aging. As a result clearance of transfused cells is dramatically facilitated (Bosman, 2013;Flatt et al, 2014).…”