Understanding the Erythrocyte Storage Lesion

Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. .
Anesthesiology (Impact Factor: 6.17). 12/2012; 117(6):1159-61. DOI: 10.1097/ALN.0b013e318272d8ac
Source: PubMed
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Available from: Gregory James Kato, Dec 01, 2014
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    ABSTRACT: Massive transfusion of blood can lead to clinical complications, including multiorgan dysfunction and even death. Such severe clinical outcomes have been associated with longer red blood cell (rbc) storage times. Collectively referred to as the rbc storage lesion, rbc storage results in multiple biochemical changes that impact intracellular processes as well as membrane and cytoskeletal properties, resulting in cellular injury in vitro. However, how the rbc storage lesion triggers pathophysiology in vivo remains poorly defined. In this study, we developed a guinea pig transfusion model with blood stored under standard blood banking conditions for 2 (new), 21 (intermediate), or 28 days (old blood). Transfusion with old but not new blood led to intravascular hemolysis, acute hypertension, vascular injury, and kidney dysfunction associated with pathophysiology driven by hemoglobin (Hb). These adverse effects were dramatically attenuated when the high-affinity Hb scavenger haptoglobin (Hp) was administered at the time of transfusion with old blood. Pathologies observed after transfusion with old blood, together with the favorable response to Hp supplementation, allowed us to define the in vivo consequences of the rbc storage lesion as storage-related posttransfusion hemolysis producing Hb-driven pathophysiology. Hb sequestration by Hp might therefore be a therapeutic modality for enhancing transfusion safety in severely ill or massively transfused patients.
    The Journal of clinical investigation 03/2012; 122(4):1444-58. DOI:10.1172/JCI59770 · 13.77 Impact Factor
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    ABSTRACT: Blood for transfusion is stored for up to 42 days. Older blood develops lesions and accumulates potentially injurious substances. Some studies report increasing toxicity as blood ages. We assessed the safety of transfused older versus newer stored blood. PubMed, Scopus, and Embase were searched using terms new and old and red blood cell and storage through May 6, 2011, for observational and randomized controlled studies comparing outcomes using transfused blood having longer and shorter storage times. Death was the outcome of interest. Twenty-one studies were identified, predominantly in cardiac surgery (n=6) and trauma (n=6) patients, including 409,966 patients. A test for heterogeneity of these studies' results was not significant for mortality (I(2)=3.7%, p=0.41). Older blood was associated with a significantly increased risk of death (odds ratio, 1.16; 95% confidence interval [CI], 1.07-1.24). Using available mortality data, 97 (95% CI, 63-199) patients need to be treated with only new blood to save one life. Subgroup analysis of these trials indicated that the increased risk was not restricted to a particular type of patient, size of trial, or amount of blood transfused. Based on available data, use of older stored blood is associated with a significantly increased risk of death.
    Transfusion 12/2011; 52(6):1184-95. DOI:10.1111/j.1537-2995.2011.03466.x · 3.57 Impact Factor
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    ABSTRACT: As stored blood ages intraerythrocytic energy sources are depleted resulting in reduced structural integrity of the membrane. Thus, stored red blood cells (RBCs) become less deformable and more fragile as they age. This fragility leads to release of cell-free hemoglobin (Hb) and formation of microparticles, submicron Hb-containing vesicles. Upon transfusion, it is likely that additional hemolysis and microparticle formation occurs due to breakdown of fragile RBCs. Release of cell-free Hb and microparticles leads to increased consumption of nitric oxide (NO), an important signaling molecule that modulates blood flow, and may promote inflammation. Stored blood may also be deficient in recently discovered blood NO synthase activity. We hypothesize that these factors play a potential role in the blood storage lesion.
    Transfusion 04/2011; 51(4):844-51. DOI:10.1111/j.1537-2995.2011.03100.x · 3.57 Impact Factor
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