Evolution of adverse changes in stored RBCs

Department of Anesthesiology, Duke University, Durham, North Carolina, United States
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 11/2007; 104(43):17063-8. DOI: 10.1073/pnas.0708160104
Source: PubMed


Recent studies have underscored questions about the balance of risk and benefit of RBC transfusion. A better understanding of the nature and timing of molecular and functional changes in stored RBCs may provide strategies to improve the balance of benefit and risk of RBC transfusion. We analyzed changes occurring during RBC storage focusing on RBC deformability, RBC-dependent vasoregulatory function, and S-nitrosohemoglobin (SNO-Hb), through which hemoglobin (Hb) O(2) desaturation is coupled to regional increases in blood flow in vivo (hypoxic vasodilation). Five hundred ml of blood from each of 15 healthy volunteers was processed into leukofiltered, additive solution 3-exposed RBCs and stored at 1-6 degrees C according to AABB standards. Blood was subjected to 26 assays at 0, 3, 8, 24 and 96 h, and at 1, 2, 3, 4, and 6 weeks. RBC SNO-Hb decreased rapidly (1.2 x 10(-4) at 3 h vs. 6.5 x 10(-4) (fresh) mol S-nitrosothiol (SNO)/mol Hb tetramer (P = 0.032, mercuric-displaced photolysis-chemiluminescence assay), and remained low over the 42-day period. The decline was corroborated by using the carbon monoxide-saturated copper-cysteine assay [3.0 x 10(-5) at 3 h vs. 9.0 x 10(-5) (fresh) mol SNO/mol Hb]. In parallel, vasodilation by stored RBCs was significantly depressed. RBC deformability assayed at a physiological shear stress decreased gradually over the 42-day period (P < 0.001). Time courses vary for several storage-induced defects that might account for recent observations linking blood transfusion with adverse outcomes. Of clinical concern is that SNO levels, and their physiological correlate, RBC-dependent vasodilation, become depressed soon after collection, suggesting that even "fresh" blood may have developed adverse biological characteristics.

  • Source
    • "In patients with hemorrhagic shock, acidosis often results from tissue hypo-perfusion and hypothermia. And the acidosis is worsened by massive transfusion of acidic stored blood products , because the pH of PRBCs decreases from 7.4 to 6.9 almost immediately after storing and even falls to as low as 6.7 after 3 weeks [4]. Furthermore, acidosis may impair almost all essential parts of the coagulation process [5] [6]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Bleeding is a common problem during resection of a retroperitoneal mass. Massive bleeding may occur in case of injury of an adjacent major vessel or organ. This case report describes a successful anesthetic management of a patient with 10 l of blood loss within three hours surgery. A 44-year-old woman who underwent an operation for resection of a retroperitoneal mass, went to a hypovolemic shock, due to acute life-threatening intra-operative bleeding, and was successfully rescued with a combination of measures, including control of surgical bleeding, supportive treatment with rapid fluid infusion, massive transfusion of blood products and administration of intravenous vasoactive agents for maintaining tissue perfusion and oxygenation, utilizing intraoperative autologous blood salvaged via cell saver, as well as prevention and treatment of complications. The patient received a total of 22 units of Packet Red Blood Cells (PRBCs), 18 units of Fresh Frozen Plasma (FFP), 10 units of cryoprecipitate, 3750 ml of her own salvage blood. Postoperatively, she was transferred to the intensive care unit (ICU) with mechanical ventilator support, where she received another 5.4 units of FFP, 10 units of cryoprecipitate. The patient developed features of early acute lung injury such as fever and hypoxemia, and was managed successfully with mechanical ventilator support for a few days. At a three-month follow-up, the patient was doing very well. This paper explores the pathogenesia, implications, prevention and treatment of the transfusion-associated complications such as acidosis, hypothermia, electrolyte abnormalities, and transfusion-related acute lung injury (TRALI). Particular attention is given to the prevention of secondary coagulopathy of the patient requiring massive blood transfusion. This case study presents a good reference for similar anesthetic scenario in the future.
    Full-text · Article · Feb 2015 · Egyptian Journal of Anaesthesia
  • Source
    • "The build up of lactic acid and fall in pH activates the phosphatase activity of diphosphoglycerate mutase, the enzyme that dephosphorylates 2,3-DPG (Figure 1). Hence levels of 2,3-DPG decline rapidly over the first week of storage (Bennett-Guerrero et al., 2007). Molecules of 2,3-DPG modulate oxygen transport by preferentially binding to deoxyhemoglobin and thus facilitate the release of oxygen in the tissues. "
    [Show abstract] [Hide abstract]
    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.
    Full-text · Article · Jun 2014 · Frontiers in Physiology
  • Source
    • "Studies addressing the question of how blood storage affects RBC deformability confirm a reduction in RBC deformability due to shape abnormalities [2] during long-term storage [1] [22] [25]. RBC deformability depends on nitric oxide (NO) availability [18] [40] and in RBCs, NO is produced by the conversion of L-arginine to L-citrulline [35] mediated by the activity of the RBC nitric oxide synthase (RBC-NOS) [11] [18] [27] [40]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: During storage, red blood cells (RBC) become more susceptible to hemolysis and it has also been shown that RBC deformability, which is influenced by RBC nitric oxide synthase (RBC-NOS) activity, decreases during blood storage while a correlation between these two parameters under storage conditions has not been investigated so far. Therefore, blood from 15 male volunteers was anticoagulated, leuko-reduced and stored as either concentrated RBC or RBC diluted in saline-adenine-glucose-mannitol (SAGM) for eight weeks at 4°C and results were compared to data obtained from freshly drawn blood. During storage, decrease of RBC deformability was related to increased mean cellular volume and increased cell lysis but also to a decrease in RBC-NOS activation. The changes were more pronounced in concentrated RBC than in RBC diluted in SAGM suggesting that the storage method affects the quality of blood. These data shed new light on mechanisms underlying the phenomenon of storage lesion and reveal that RBC-NOS activation and possibly nitric oxide production in RBC are key elements that are influenced by storage and in turn alter deformability. Further studies should therefore also focus on improving these parameters during storage to improve the quality of stored blood with respect to blood transfusion.
    Full-text · Article · Jun 2014 · Clinical hemorheology and microcirculation
Show more