Red Blood Cell Storage: How Long Is Too Long?
2013; Elsevier BV; Volume: 96; Issue: 5 Linguagem: Inglês
10.1016/j.athoracsur.2013.05.116
ISSN1552-6259
AutoresColleen G. Koch, Priscilla Figueroa, Liang Li, Joseph F. Sabik, Tomislav Mihaljević, Eugene H. Blackstone,
Tópico(s)Hemoglobin structure and function
ResumoRed blood cells (RBCs) undergo biochemical and structural changes during storage, commonly referred to as the "storage lesion." Evidence suggests that the longer the RBC product is stored, the less effective is the transfused blood. Many studies linking morbidity to transfusion have not considered duration of RBC storage as a variable that may modulate the effect. In addition, the effects of supply and demand and RBC inventory management strategies have been incompletely investigated. It is possible to envision a blood management system based on modern inventory management strategies that could greatly reduce storage duration. Red blood cells (RBCs) undergo biochemical and structural changes during storage, commonly referred to as the "storage lesion." Evidence suggests that the longer the RBC product is stored, the less effective is the transfused blood. Many studies linking morbidity to transfusion have not considered duration of RBC storage as a variable that may modulate the effect. In addition, the effects of supply and demand and RBC inventory management strategies have been incompletely investigated. It is possible to envision a blood management system based on modern inventory management strategies that could greatly reduce storage duration. Although there are well-described risks associated with red blood cell (RBC) transfusion [1Koch C. Li L. Figueroa P. Mihaljevic T. Svensson L. Blackstone E.H. Transfusion and pulmonary morbidity after cardiac surgery.Ann Thorac Surg. 2009; 88: 1410-1418Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar, 2Koch C.G. Li L. Duncan A.I. et al.Transfusion in coronary artery bypass grafting is associated with reduced long-term survival.Ann Thorac Surg. 2006; 81: 1650-1657Abstract Full Text Full Text PDF PubMed Scopus (414) Google Scholar, 3Koch C.G. Li L. Van Wagoner D.R. Duncan A.I. Gillinov A.M. Blackstone E.H. Red cell transfusion is associated with an increased risk for postoperative atrial fibrillation.Ann Thorac Surg. 2006; 82: 1747-1756Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar, 4Koch C.G. Li L. Duncan A.I. et al.Morbidity and mortality risk associated with red blood cell and blood-component transfusion in isolated coronary artery bypass grafting.Crit Care Med. 2006; 34: 1608-1616Crossref PubMed Scopus (711) Google Scholar, 5Habib R.H. Zacharias A. Schwann T.A. et al.Role of hemodilutional anemia and transfusion during cardiopulmonary bypass in renal injury after coronary revascularization: implications on operative outcome.Crit Care Med. 2005; 33: 1749-1756Crossref PubMed Scopus (240) Google Scholar, 6Ferraris V.A. Davenport D.L. Saha S.P. Bernard A. Austin P.C. Zwischenberger J.B. Intraoperative transfusion of small amounts of blood heralds worse postoperative outcome in patients having noncardiac thoracic operations.Ann Thorac Surg. 2011; 91: 1674-1680Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar, 7Murphy G.J. Reeves B.C. Rogers C.A. Rizvi S.I. Culliford L. Angelini G.D. Increased mortality, postoperative morbidity, and cost after red blood cell transfusion in patients having cardiac surgery.Circulation. 2007; 116: 2544-2552Crossref PubMed Scopus (998) Google Scholar], suitability of transfusion in relation to RBC shelf life has not been well established. Currently, it is determined by in vitro RBC structural integrity and in vivo recovery [8Moroff G. Sohmer P.R. Button L.N. Proposed standardization of methods for determining the 24-hour survival of stored red cells.Transfusion. 1984; 24: 109-114Crossref PubMed Scopus (144) Google Scholar, 9Dumont L.J. AuBuchon J.P. Evaluation of proposed FDA criteria for the evaluation of radiolabeled red cell recovery trials.Transfusion. 2008; 48: 1053-1060Crossref PubMed Scopus (188) Google Scholar, 10FDA Workshop on Red Cells Stored in Additive Solution Systems. April 25, 1985, Bethesda, MD.Google Scholar], but standards addressing in vivo RBC functionality after transfusion are lacking [11Elfath M.D. Is it time to focus on preserving the functionality of red blood cells during storage?.Transfusion. 2006; 46: 1469-1470Crossref PubMed Scopus (5) Google Scholar], in part because of the technical challenges of measuring tissue oxygen delivery in a clinically useful manner. What is indisputable is that RBCs undergo biochemical and morphologic changes during storage, and evidence suggests that the longer the RBC product is stored, the less effective is the transfused blood. Most studies linking morbidity to RBC transfusion have not considered duration of RBC storage as a variable that may modulate the effect. This is not surprising because if multiple units are transfused, each may have been stored for a different length of time. Thus, we define storage duration and its determinants and review experimental studies detailing changes in RBCs during storage that limit their shelf life, clinical evidence of adverse effects of RBC transfusion without regard to storage duration, and more limited and conflicting evidence of an association between storage duration and adverse events. Finally, we suggest strategies that could be used to substantially shorten RBC storage duration. Storage duration is the time between blood donation and transfusion. The maximum US Food and Drug Administration (FDA)-approved storage duration is dependent on the storage system, but for most RBC products, the FDA limits storage duration to 42 days. The limit for storage duration is primarily related to the degree of in vitro hemolysis at the end of storage and the related percentage of transfused RBCs remaining in the circulation 24 hours after transfusion [8Moroff G. Sohmer P.R. Button L.N. Proposed standardization of methods for determining the 24-hour survival of stored red cells.Transfusion. 1984; 24: 109-114Crossref PubMed Scopus (144) Google Scholar, 9Dumont L.J. AuBuchon J.P. Evaluation of proposed FDA criteria for the evaluation of radiolabeled red cell recovery trials.Transfusion. 2008; 48: 1053-1060Crossref PubMed Scopus (188) Google Scholar, 10FDA Workshop on Red Cells Stored in Additive Solution Systems. April 25, 1985, Bethesda, MD.Google Scholar]. Duration of storage is dependent on blood type, how inventory is managed, and dynamics of supply and demand. Thus, units of less common blood types, such as AB negative, tend to be stored longer than more common types, particularly type O, because of less demand [12Raat N.J. Berends F. Verhoeven A.J. de Korte D. Ince C. The age of stored red blood cell concentrates at the time of transfusion.Transfus Med. 2005; 15: 419-423Crossref PubMed Scopus (28) Google Scholar]. Currently, blood banks dispense blood on a first-in first-out basis, with the oldest unit selected first. This strategy guarantees a preponderance of transfusions with blood that has been stored longer. In one study, one-third of transfused units were stored longer than 21 days [12Raat N.J. Berends F. Verhoeven A.J. de Korte D. Ince C. The age of stored red blood cell concentrates at the time of transfusion.Transfus Med. 2005; 15: 419-423Crossref PubMed Scopus (28) Google Scholar]. Time-dependent change, known as the "storage lesion," reflect deterioration of RBCs with storage (Table 1) [13Spinella P.C. Sparrow R.L. Hess J.R. Norris P.J. Properties of stored red blood cells: understanding immune and vascular reactivity.Transfusion. 2011; 51: 894-900Crossref PubMed Scopus (54) Google Scholar, 14McFaul S.J. Bowman P.D. Villa V.M. Gutierrez-Ibanez M.J. Johnson M. Smith D. Hemoglobin stimulates mononuclear leukocytes to release interleukin-8 and tumor necrosis factor alpha.Blood. 1994; 84: 3175-3181PubMed Google Scholar, 15Vandromme M.J. McGwin Jr., G. Weinberg J.A. Blood transfusion in the critically ill: does storage age matter?.Scand J Trauma Resusc Emerg Med. 2009; 17: 35Crossref PubMed Scopus (24) Google Scholar, 16Berezina T.L. Zaets S.B. Morgan C. et al.Influence of storage on red blood cell rheological properties.J Surg Res. 2002; 102: 6-12Abstract Full Text PDF PubMed Scopus (305) Google Scholar, 17Relevy H. Koshkaryev A. Manny N. Yedgar S. Barshtein G. Blood banking-induced alteration of red blood cell flow properties.Transfusion. 2008; 48: 136-146PubMed Google Scholar, 18Bennett-Guerrero E. Veldman T.H. Doctor A. et al.Evolution of adverse changes in stored RBCs.Proc Natl Acad Sci U S A. 2007; 104: 17063-17068Crossref PubMed Scopus (494) Google Scholar, 19Reynolds J.D. Ahearn G.S. Angelo M. Zhang J. Cobb F. Stamler J.S. S-nitrosohemoglobin deficiency: a mechanism for loss of physiological activity in banked blood.Proc Natl Acad Sci U S A. 2007; 104: 17058-17062Crossref PubMed Scopus (246) Google Scholar, 20Chaplin Jr., H. Beutler E. Collins J.A. Giblett E.R. Polesky H.F. Current status of red-cell preservation and availability in relation to the developing national blood policy.N Engl J Med. 1974; 291: 68-74Crossref PubMed Scopus (17) Google Scholar, 21Hess J.R. Red cell changes during storage.Transfus Apher Sci. 2010; 43: 51-59Abstract Full Text Full Text PDF PubMed Scopus (213) Google Scholar]. These changes mean that transfusion may result in delivery of high concentrations of RBC constituents, such as hemoglobin and free iron. Shedding of RBC microvesicles, whose surfaces have been found to be both procoagulant and proinflammatory, increases concentrations of biologically active lipids[13Spinella P.C. Sparrow R.L. Hess J.R. Norris P.J. Properties of stored red blood cells: understanding immune and vascular reactivity.Transfusion. 2011; 51: 894-900Crossref PubMed Scopus (54) Google Scholar, 14McFaul S.J. Bowman P.D. Villa V.M. Gutierrez-Ibanez M.J. Johnson M. Smith D. Hemoglobin stimulates mononuclear leukocytes to release interleukin-8 and tumor necrosis factor alpha.Blood. 1994; 84: 3175-3181PubMed Google Scholar, 22Bosman G.J. Lasonder E. Luten M. et al.The proteome of red cell membranes and vesicles during storage in blood bank conditions.Transfusion. May 2008; 48: 827-835PubMed Google Scholar, 23Silliman C.C. Clay K.L. Thurman G.W. Johnson C.A. Ambruso D.R. Partial characterization of lipids that develop during the routine storage of blood and prime the neutrophil NADPH oxidase.J Lab Clin Med. 1994; 124: 684-694PubMed Google Scholar, 24Greenwalt T.J. The how and why of exocytic vesicles.Transfusion. 2006; 46: 143-152Crossref PubMed Scopus (179) Google Scholar, 25Sweeney J. Kouttab N. Kurtis J. Stored red blood cell supernatant facilitates thrombin generation.Transfusion. 2009; 49: 1569-1579Crossref PubMed Scopus (58) Google Scholar]. These constituents, along with biochemical and morphologic changes, may contribute to adverse clinical events.Table 1Characteristics of the Storage LesionReprinted from Vandromme MJ, et al, Scand J Trauma Resusc Emerg Med 2009;17:35 15Vandromme M.J. McGwin Jr., G. Weinberg J.A. Blood transfusion in the critically ill: does storage age matter?.Scand J Trauma Resusc Emerg Med. 2009; 17: 35Crossref PubMed Scopus (24) Google Scholar with permission.Storage EffectConsequencesChanges to red cell structure and function Cellular membrane changesErythrocyte shape changeDecreased survivability Decreased 2,3-diphosphoglycerateIncreased oxygen affinityDecreased oxygen delivery Decreased adenosine triphosphateErythrocyte shape changeIncreased cell fragilityLess resistance to oxidative stressChanges in red cell storage medium Accumulation of bioactive substances (cytokines, histamines, lipids, enzymes)Increased oxidative environmentFebrile transfusion reactionsImmunologic activation/suppression Open table in a new tab Baek and colleagues [26Baek J.H. D'Agnillo F. Vallelian F. et al.Hemoglobin-driven pathophysiology is an in vivo consequence of the red blood cell storage lesion that can be attenuated in guinea pigs by haptoglobin therapy.J Clin Invest. 2012; 122: 1444-1458Crossref PubMed Scopus (223) Google Scholar] hypothesized that pathophysiologic processes among patients with hemolytic anemia results in part from elevated concentrations of extracellular hemoglobin thought to drive the negative effects of vascular dysfunction and heme-driven oxidative reactions. Using a guinea pig exchange transfusion model, they found that transfusing older RBCs resulted in significantly more abnormal necrotic regions of the aortic root 24 hours after transfusion and higher amounts of collagen deposition 48 hours after transfusion, along with nephrosis and renal tubular degeneration. Coinfusion of haptoglobin, a free hemoglobin binder, with older stored blood attenuated these effects (Fig 1). One unit of RBCs contains approximately 200 mg of iron; if 25% of each unit is cleared by 24 hours, as is acceptable by current standards, this constitutes a substantial iron load to the monocyte/macrophage system [27Hod E.A. Zhang N. Sokol S.A. et al.Transfusion of red blood cells after prolonged storage produces harmful effects that are mediated by iron and inflammation.Blood. 2010; 115: 4284-4292Crossref PubMed Scopus (367) Google Scholar]. Using a murine model, Hod and colleagues [27Hod E.A. Zhang N. Sokol S.A. et al.Transfusion of red blood cells after prolonged storage produces harmful effects that are mediated by iron and inflammation.Blood. 2010; 115: 4284-4292Crossref PubMed Scopus (367) Google Scholar] found that prolonged RBC storage was associated with increased plasma nontransferrin-bound iron, leading to acute tissue iron deposition and inflammation. This nontransferrin-bound iron enhanced bacterial growth in vitro. In a recent clinical investigation, extravascular hemolysis and circulating nontransferrin-bound iron were measured in relationship to duration of RBC storage (fresh, 3–7 days and 40–42 days, respectively) using autologous cells from 14 healthy volunteers [28Hod E.A. Brittenham G.M. Billote G.B. et al.Transfusion of human volunteers with older, stored red blood cells produces extravascular hemolysis and circulating non-transferrin-bound iron.Blood. 2011; 118: 6675-6682Crossref PubMed Scopus (224) Google Scholar]. Older stored units were associated with increased concentrations of nontransferrin-bound iron from rapid clearance of older blood, and this correlated with enhanced proliferation of an in vitro pathogenic strain of Escherichia coli. The investigators hypothesized that increased infectious risk, cytotoxicity, and thrombosis from transfusion may be related, in part, to production of circulating nontransferrin-bound iron. Patients with transfusion iron overload, as well as those with hereditary forms of hemochromatosis, may have circulating nontransferrin-bound iron levels similar to those measured in healthy volunteers 4 hours after RBC transfusion; these patients are known to be at an increased risk for acute and chronic infections [28Hod E.A. Brittenham G.M. Billote G.B. et al.Transfusion of human volunteers with older, stored red blood cells produces extravascular hemolysis and circulating non-transferrin-bound iron.Blood. 2011; 118: 6675-6682Crossref PubMed Scopus (224) Google Scholar, 29Khan F.A. Fisher M.A. Khakoo R.A. Association of hemochromatosis with infectious diseases: expanding spectrum.Int J Infect Dis. 2007; 11: 482-487Abstract Full Text Full Text PDF PubMed Scopus (139) Google Scholar]. Stored RBCs accumulate lactic acid and potassium, and pH progressively decreases (Fig 2) [15Vandromme M.J. McGwin Jr., G. Weinberg J.A. Blood transfusion in the critically ill: does storage age matter?.Scand J Trauma Resusc Emerg Med. 2009; 17: 35Crossref PubMed Scopus (24) Google Scholar, 18Bennett-Guerrero E. Veldman T.H. Doctor A. et al.Evolution of adverse changes in stored RBCs.Proc Natl Acad Sci U S A. 2007; 104: 17063-17068Crossref PubMed Scopus (494) Google Scholar]. Routine storage of RBCs results in an early loss (within hours) of nitric oxide bioactivity, which may lead to impaired vasodilation in response to hypoxia and subsequent compromised blood flow. Repletion of S-nitrosohemoglobin may improve transfusion efficacy [19Reynolds J.D. Ahearn G.S. Angelo M. Zhang J. Cobb F. Stamler J.S. S-nitrosohemoglobin deficiency: a mechanism for loss of physiological activity in banked blood.Proc Natl Acad Sci U S A. 2007; 104: 17058-17062Crossref PubMed Scopus (246) Google Scholar]. In an animal model, RBCs stored for 5 to 6 weeks had reduced oxygen-delivering capacity compared with RBCs stored for 2 to 3 weeks when a low hematocrit value was present [30Raat N.J. Verhoeven A.J. Mik E.G. et al.The effect of storage time of human red cells on intestinal microcirculatory oxygenation in a rat isovolemic exchange model.Crit Care Med. 2005; 33 (discussion 238–9): 39-45Crossref PubMed Scopus (110) Google Scholar]. In a study examining the effect of storage duration of strain-specific rat blood on tissue oxygen delivery, Rigamonti and colleagues [31Rigamonti A. McLaren A.T. Mazer C.D. et al.Storage of strain-specific rat blood limits cerebral tissue oxygen delivery during acute fluid resuscitation.Br J Anaesth. 2008; 100: 357-364Crossref PubMed Scopus (12) Google Scholar] found that fresh blood resulted in higher tissue oxygen tension and increased regional cerebral blood flow. With longer storage, RBCs change shape from a normal biconcave disk to echinocytes and spheroechinocytes (Figs 2, 3) [32Vandromme M.J. McGwin Jr., G. Weinberg J.A. Blood transfusion in the critically ill: does storage age matter?.Scand J Trauma Resusc Emerg Med. 2009; 17: 35Crossref PubMed Scopus (63) Google Scholar, 33Almac E. Ince C. The impact of storage on red cell function in blood transfusion.Best Pract Res Clin Anaesthesiol. 2007; 21: 195-208Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar]. These changes reduce their deformability and increase their likelihood of occluding the microcirculation (Fig 4) [32Vandromme M.J. McGwin Jr., G. Weinberg J.A. Blood transfusion in the critically ill: does storage age matter?.Scand J Trauma Resusc Emerg Med. 2009; 17: 35Crossref PubMed Scopus (63) Google Scholar, 33Almac E. Ince C. The impact of storage on red cell function in blood transfusion.Best Pract Res Clin Anaesthesiol. 2007; 21: 195-208Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar]. The resulting decrease in tissue blood flow may explain why stored blood does not fully correct anemia-associated deficits in tissue oxygen delivery [19Reynolds J.D. Ahearn G.S. Angelo M. Zhang J. Cobb F. Stamler J.S. S-nitrosohemoglobin deficiency: a mechanism for loss of physiological activity in banked blood.Proc Natl Acad Sci U S A. 2007; 104: 17058-17062Crossref PubMed Scopus (246) Google Scholar]. The cause of decreased deformability is thought to be, in part, oxidative-induced membrane changes or depletion of adenosine triphosphate and 2, 3-diphosphoglycerate [16Berezina T.L. Zaets S.B. Morgan C. et al.Influence of storage on red blood cell rheological properties.J Surg Res. 2002; 102: 6-12Abstract Full Text PDF PubMed Scopus (305) Google Scholar].Fig 4Implications of the storage lesion: reduced red blood cell deformability and impaired microvascular tissue flow. (A) Normal capillary. (B) Capillary blocked by abnormally shaped red blood cells.View Large Image Figure ViewerDownload (PPT) At 2 weeks of storage, RBCs demonstrate enhanced aggregability [17Relevy H. Koshkaryev A. Manny N. Yedgar S. Barshtein G. Blood banking-induced alteration of red blood cell flow properties.Transfusion. 2008; 48: 136-146PubMed Google Scholar]. Longer RBC storage and white blood cell burden increase the number of RBCs adhering to vascular endothelium and the strength of this adhesion. Leukocyte reduction results in less adhesion [34Anniss A.M. Sparrow R.L. Storage duration and white blood cell content of red blood cell (RBC) products increases adhesion of stored RBCs to endothelium under flow conditions.Transfusion. 2006; 46: 1561-1567Crossref PubMed Scopus (61) Google Scholar]. As RBC storage duration increases, concentration of microvesicles increases [25Sweeney J. Kouttab N. Kurtis J. Stored red blood cell supernatant facilitates thrombin generation.Transfusion. 2009; 49: 1569-1579Crossref PubMed Scopus (58) Google Scholar]. Many of these microvesicles express phosphatidylserine, which facilitates thrombin generation in vitro. This is a possible mechanism by which stored RBCs contribute to thrombotic and other complications associated with transfusion (Table 1; Fig 5) [25Sweeney J. Kouttab N. Kurtis J. Stored red blood cell supernatant facilitates thrombin generation.Transfusion. 2009; 49: 1569-1579Crossref PubMed Scopus (58) Google Scholar, 35Jy W. Ricci M. Shariatmadar S. Gomez-Marin O. Horstman L.H. Ahn Y.S. Microparticles in stored red blood cells as potential mediators of transfusion complications.Transfusion. 2011; 51: 886-893Crossref PubMed Scopus (111) Google Scholar, 36Rubin O. Crettaz D. Tissot J.D. Lion N. Microparticles in stored red blood cells: submicron clotting bombs?.Blood Transfus. 2010; : s31-s38PubMed Google Scholar]. The morbidity associated with RBC transfusion is likely multifactorial, and separating out the incremental effect of storage duration is difficult. Thus, before presenting the limited and conflicting information about clinical adverse effects of RBC storage duration, we present evidence that transfusion, irrespective of storage duration, is associated with risks for complications. Most investigations reporting morbidity risks associated with transfusion are cohort studies rather than more definitive randomized trials. Nonetheless, they reveal complications associated with transfusion—infection, transfusion-related acute lung injury (TRALI), febrile nonhemolytic reactions, and transfusion-associated circulatory overload —for which there is general consensus of a causal link. Immunomodulation, with downregulation of the immune system, is associated with RBC transfusion and may increase susceptibility to infections [37Klein H.G. Immunomodulatory aspects of transfusion: a once and future risk?.Anesthesiology. 1999; 91: 861-865Crossref PubMed Scopus (134) Google Scholar]. Risk for bacteremia/septicemia and superficial and deep sternal wound infections appears to increase in a dose-related manner as the number of RBC units received increases [38Banbury M.K. Brizzio M.E. Rajeswaran J. Lytle B.W. Blackstone E.H. Transfusion increases the risk of postoperative infection after cardiovascular surgery.J Am Coll Surg. 2006; 202: 131-138Abstract Full Text Full Text PDF PubMed Scopus (177) Google Scholar]. Variables related to specifics of storage and processing, such as degree of leukocyte reduction, are implicated in transfusion-related immunomodulation, which may lead to infection [13Spinella P.C. Sparrow R.L. Hess J.R. Norris P.J. Properties of stored red blood cells: understanding immune and vascular reactivity.Transfusion. 2011; 51: 894-900Crossref PubMed Scopus (54) Google Scholar, 39Sparrow R.L. Patton K.A. Supernatant from stored red blood cell primes inflammatory cells: influence of prestorage white cell reduction.Transfusion. 2004; 44: 722-730Crossref PubMed Scopus (69) Google Scholar]; however, the relationship between leukocyte reduction and infectious complications is unclear. For example, a recent double-blinded randomized trial in patients undergoing colorectal operations reported that leukocyte depletion did not reduce infectious complications associated with transfusion. Infections were higher in patients who underwent RBC transfusions compared with those who did not; however, infectious complications were similar when RBCs depleted of leukocytes were used and when RBCs that were not depleted of leukocytes were used [40Titlestad I.L. Ebbesen L.S. Ainsworth A.P. Lillevang S.T. Qvist N. Georgsen J. Leukocyte-depletion of blood components does not significantly reduce the risk of infectious complications. Results of a double-blinded, randomized study.Int J Colorectal Dis. 2001; 16: 147-153Crossref PubMed Scopus (79) Google Scholar]. Transfusions during and after cardiac operations are associated with higher prevalence of respiratory complications, acute respiratory distress syndrome, and longer intensive care unit and hospital stays [1Koch C. Li L. Figueroa P. Mihaljevic T. Svensson L. Blackstone E.H. Transfusion and pulmonary morbidity after cardiac surgery.Ann Thorac Surg. 2009; 88: 1410-1418Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar]. It is unclear whether pulmonary morbidity associated with transfusion is related to TRALI or transfusion-associated circulatory overload, or both, or lung damage from cardiopulmonary bypass [1Koch C. Li L. Figueroa P. Mihaljevic T. Svensson L. Blackstone E.H. Transfusion and pulmonary morbidity after cardiac surgery.Ann Thorac Surg. 2009; 88: 1410-1418Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar, 41Popovsky M.A. Transfusion-associated circulatory overload: the plot thickens.Transfusion. 2009; 49: 2-4Crossref PubMed Scopus (0) Google Scholar, 42Popovsky M.A. Audet A.M. Andrzejewski Jr., C. Transfusion-associated circulatory overload in orthopedic surgery patients: a multi-institutional study.Immunohematology. 1996; 12: 87-89PubMed Google Scholar, 43Popovsky M.A. Transfusion and lung injury.Transfus Clin Biol. 2001; 8: 272-277Crossref PubMed Scopus (86) Google Scholar, 44Kleinman S. Caulfield T. Chan P. et al.Toward an understanding of transfusion-related acute lung injury: statement of a consensus panel.Transfusion. 2004; 44: 1774-1789Crossref PubMed Scopus (579) Google Scholar, 45Kopko P.M. Holland P.V. Transfusion-related acute lung injury.Br J Haematol. 1999; 105: 322-329Crossref PubMed Scopus (132) Google Scholar]. Special efforts to reduce TRALI-related pulmonary morbidity have been the subject of consensus statements, with management strategies recommended to identify and reduce risk in the transfused population. A number of investigators report an increase in early and late mortality after surgical interventions in patients who receive perioperative RBC transfusions [2Koch C.G. Li L. Duncan A.I. et al.Transfusion in coronary artery bypass grafting is associated with reduced long-term survival.Ann Thorac Surg. 2006; 81: 1650-1657Abstract Full Text Full Text PDF PubMed Scopus (414) Google Scholar, 4Koch C.G. Li L. Duncan A.I. et al.Morbidity and mortality risk associated with red blood cell and blood-component transfusion in isolated coronary artery bypass grafting.Crit Care Med. 2006; 34: 1608-1616Crossref PubMed Scopus (711) Google Scholar, 46Koch C.G. Khandwala F. Li L. Estafanous F.G. Loop F.D. Blackstone E.H. Persistent effect of red cell transfusion on health-related quality of life after cardiac surgery.Ann Thorac Surg. 2006; 82: 13-20Abstract Full Text Full Text PDF PubMed Scopus (96) Google Scholar, 47Engoren M.C. Habib R.H. Zacharias A. Schwann T.A. Riordan C.J. Durham S.J. Effect of blood transfusion on long-term survival after cardiac operation.Ann Thorac Surg. 2002; 74: 1180-1186Abstract Full Text Full Text PDF PubMed Scopus (527) Google Scholar, 48Kuduvalli M. Oo A.Y. Newall N. et al.Effect of peri-operative red blood cell transfusion on 30-day and 1-year mortality following coronary artery bypass surgery.Eur J Cardiothorac Surg. 2005; 27: 592-598Crossref PubMed Scopus (228) Google Scholar]. Both Hajjar and colleagues [49Hajjar L.A. Vincent J.L. Galas F.R. et al.Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial.JAMA. 2010; 304: 1559-1567Crossref PubMed Scopus (776) Google Scholar] and Van Straten and associates [50van Straten A.H. Bekker M.W. Soliman Hamad M.A. et al.Transfusion of red blood cells: the impact on short-term and long-term survival after coronary artery bypass grafting, a ten-year follow-up.Interact Cardiovasc Thorac Surg. 2010; 10: 37-42Crossref PubMed Scopus (86) Google Scholar] observed that the number of RBC units transfused was an independent risk factor for early death after cardiac operations. In contrast, others have not found associations of transfusion with adverse outcomes; a randomized trial of liberal versus restrictive transfusion strategies for high-risk patients undergoing hip operations demonstrated similar postoperative complications and functional outcomes, including comparable inability to walk independently at 60 days. These authors took length of RBC storage and leukocyte reduction status into consideration [51Carson J.L. Terrin M.L. Noveck H. et al.Liberal or restrictive transfusion in high-risk patients after hip surgery.N Engl J Med. 2011; 365: 2453-2462Crossref PubMed Scopus (967) Google Scholar]. Nevertheless, study investigators suggested that in the absence of anemia symptoms, it is appropriate to withhold transfusion in the elderly, just as others have suggested for critically ill patients [52Hebert P.C. Wells G. Blajchman M.A. et al.A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group.N Engl J Med. 1999; 340: 409-417Crossref PubMed Scopus (4021) Google Scholar]. Clinical investigations in trauma and cardiac surgical procedures suggest an association between longer RBC storage and adverse outcomes. Increased storage duration has been reported to be an independent risk factor for postinjury multiple organ failure [53Zallen G. Offner P.J. Moore E.E. et al.Age of transfused blood is an independent risk factor for postinjury multiple organ failure.Am J Surg. 1999; 178: 570-572Abstract Full Text Full Text PDF PubMed Scopus (447) Google Scholar], infection [54Offner P.J. Moore E.E. Biffl W.L. Johnson J.L. Silliman C.C. Increased rate of infection associated with transfusion of old blood after severe injury.Arch Surg. 2002; 137 (discussion 716–7): 711-716Crossref PubMed Scopus (294) Google Scholar], deep vein thrombosis [55Spinella P.C. Carroll C.L. Staff I. et al.Duration of red blood cell storage is associated with increased incidence of deep vein thrombosis and in hospital mortality in patients with traumatic injuries.Crit Care. 2009; 13: R151Crossref PubMed Scopus (190) Google Scholar], and hospital mortality [55Spinella P.C. Carroll C.L. Staff I. et al.Duration of red blood cell storage is associated with increased incidence of deep vein thrombosis and in hospital mortality in patients with traumatic injuries.Crit Care. 2009; 13: R151Crossref PubMed Scopus (190) Google Scholar]; the latter 2 are particularly associated with blood stored 28 days or longer. In an acute care facility setting of 4,933 patients admitted with the diagnosis of cardiovascular disease, Eikelboom and colleagues [56Eikelboom JW, Cook RJ, Liu Y, Heddle NM. Duration of red cell storage before transfusion and in-hospital mortality. Am Heart J 159:737–43.e731.Google Scholar] found a modest graded association between longer RBC storage and mortality. In patients undergoing cardiac operations, longer RBC storage is associated with increased postoperative length of stay and renal complications [57Sanders J. Patel S. Cooper J. et al.Red blood cell storage is associated with length of stay and renal complications after cardiac surgery.Transfusion. 2011; 51: 2286-2294Crossref PubMed Scopus (56) Google Scholar]. Leal-Noval and colleagues [58Leal-Noval S.R. Munoz-Gomez M. Arellano-Orden V. et al.Impact of age of transfused blood on cerebral oxygenation in male patients with severe traumatic brain injury.Crit Care Med. 2008; 36: 1290-1296Crossref PubMed Scopus (137) Google Scholar] reported that transfusion of RBCs increased cerebral oxygenation in patients with severe traumatic brain injury, except in those who received RBCs stored longer than 19 days. In critically ill trauma patients, Kiraly and colleagues [59Kiraly L.N. Underwood S. Differding J.A. Schreiber M.A. Transfusion of aged packed red blood cells results in decreased tissue oxygenation in critically injured trauma patients.J Trauma. 2009; 67: 29-32Crossref PubMed Scopus (107) Google Scholar] noted a decrease in peripheral tissue oxygenation in patients who received blood stored longer than 21 days. Blood stored longer has been associated with increased risk in other settings: Pettila and associates [60Pettila V. Westbrook A.J. Nichol A.D. et al.Age of red blood cells and mortality in the critically ill.Crit Care. 2011; 15: R116Crossref PubMed Scopus (77) Google Scholar] reported that exposure to older RBCs was associated with increased risk of death in the critical care setting. In pediatric cardiac operations, Ranucci and colleagues [61Ranucci M. Carlucci C. Isgro G. et al.Duration of red blood cell storage and outcomes in pediatric cardiac surgery: an association found for pump prime blood.Crit Care. 2009; 13: R207Crossref PubMed Scopus (56) Google Scholar] found a risk-adjusted association between older RBCs used for priming the cardiopulmonary bypass machine and postoperative morbidity in pediatric patients. In the percutaneous coronary intervention population, Robinson and coworkers [62Robinson S.D. Janssen C. Fretz E.B. et al.Red blood cell storage duration and mortality in patients undergoing percutaneous coronary intervention.Am Heart J. 2010; 159: 876-881Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar] reported an increase in postprocedure mortality at 30 days after coronary interventions. The authors noted that use of older RBCs may have contributed to the increased hazard for death. Weinberg and colleagues [63Weinberg J.A. McGwin Jr., G. Griffin R.L. et al.Age of transfused blood: an independent predictor of mortality despite universal leukoreduction.J Trauma. 2008; 65 (discussion 282–4): 279-282Crossref PubMed Scopus (177) Google Scholar] found that larger volumes of transfusion—especially with RBCs stored longer than 2 weeks—were associated with higher mortality. In a large study of cardiac surgical procedures, patients who received blood stored longer than 2 weeks experienced more postoperative complications as a composite end point than did those receiving blood stored less than 2 weeks [64Koch C.G. Li L. Sessler D.I. et al.Duration of red-cell storage and complications after cardiac surgery.N Engl J Med. 2008; 358: 1229-1239Crossref PubMed Scopus (1125) Google Scholar]. Both short- and long-term survival were reduced. These studies suggest that the shelf life of stored RBCs should be limited to about 2 weeks. However, other studies report no apparent relation of storage duration to clinical outcomes. Walsh and colleagues [65Walsh T.S. McArdle F. McLellan S.A. et al.Does the storage time of transfused red blood cells influence regional or global indexes of tissue oxygenation in anemic critically ill patients?.Crit Care Med. 2004; 32: 364-371Crossref PubMed Scopus (207) Google Scholar] studied 22 critically ill euvolemic patients and reported no clinically significant adverse effects of longer RBC storage on gastric tonometry or global indices of tissue oxygenation. Edgren and colleagues [66Edgren G. Kamper-Jorgensen M. Eloranta S. et al.Duration of red blood cell storage and survival of transfused patients (CME).Transfusion. 2010; 50: 1185-1195Crossref PubMed Scopus (122) Google Scholar] reported a similar 7-day risk of death among transfused patients for all durations of storage except RBCs stored 30 to 42 days. The authors surmised that these findings may have been due to "weak" confounding. In a cohort of 9 healthy volunteers, Weiskopf and colleagues [67Weiskopf R.B. Feiner J. Hopf H. et al.Fresh blood and aged stored blood are equally efficacious in immediately reversing anemia-induced brain oxygenation deficits in humans.Anesthesiology. 2006; 104: 911-920Crossref PubMed Scopus (134) Google Scholar] found that fresh and stored blood were similarly effective in reducing brain oxygenation deficits. Yap and colleagues [68Yap C.H. Lau L. Krishnaswamy M. Gaskell M. Yii M. Age of transfused red cells and early outcomes after cardiac surgery.Ann Thorac Surg. 2008; 86: 554-559Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar] studied 670 patients undergoing cardiac operations who received an admixture of RBC units of varying storage duration and reported that the total amount of RBCs transfused, rather than storage duration, was associated with early postoperative morbidity and mortality. Thus, controversy continues and may or may not be resolved by ongoing randomized trials for RBC storage duration. For example, CT.gov lists current storage duration studies—NCT00458783, NCT00991341, and NCT01319552—that are under way in the United States. Certainly, conservation programs can manage modifiable factors that place patients at increased risk for receiving an RBC transfusion or experiencing its adverse effects. Current first-in first-out RBC inventory optimization is focused on minimizing the number of expired, ie, wasted, products. To avoid product expiration, hospitals reduce the number of new shipments they receive, and blood distribution centers export excess, usually older, products to locations with greater demand. In recent years, however, new models of inventory management have emerged in the retail sector to reduce inventory shelf time in favor of just-in-time delivery of products. Might these more dynamic strategies work in blood banking to further reduce storage duration? A model already exists. Platelets expire 5 days after donation. Managing platelet inventory requires hourly monitoring and more frequent deliveries from the blood collection agency. With this infrastructure in place, it is attractive to contemplate an RBC distribution system that works the same way to reduce RBC storage duration to 14 days or less. The effect of supply versus demand has been incompletely investigated. Atkinson and colleagues [69Atkinson M.P. Fontaine M.J. Goodnough L.T. Wein L.M. A novel allocation strategy for blood transfusions: investigating the tradeoff between the age and availability of transfused blood.Transfusion. 2012; 52: 108-117Crossref PubMed Scopus (26) Google Scholar] simulated a last-in first-out management strategy in a large tertiary care–based blood collection center and transfusion service. They found that mean storage duration and blood availability were highly sensitive to supply and demand. When the supply-to-demand ratio was less than 0.98, mean age of RBCs transfused was less than 1 week. However, when supply exceeded demand by 6% or more, a last-in first-out strategy resulted in a mean RBC storage duration of 35 days or more. Evidence that deterioration of RBC units contributes to the adverse effects of transfusion is difficult to separate from the apparent dose-dependent effect of multiple transfusions. This is in part related to the different storage durations among transfused units. Thus, limits on effective shelf life of RBCs have yet to be established. In theory, it is possible to envision a blood management system based on modern inventory management strategies that could greatly reduce storage duration.
Referência(s)