Transfusion-Related Acute Lung Injury
2005; Elsevier BV; Volume: 80; Issue: 6 Linguagem: Inglês
10.1016/s0025-6196(11)61531-0
ISSN1942-5546
AutoresOgnjen Gajic, S. Breanndan Moore,
Tópico(s)Hemoglobin structure and function
ResumoTransfusion-related acute lung injury (TRALI) is characterized by the sudden development of noncardiogenic pulmonary edema (acute lung injury) after transfusion of blood products. Poor awareness of TRALI outside of the blood transfusion medicine community has led to a serious underestimation of this condition, currently the most important severe complication of blood transfusion. Concern for the transfer of donor antileukocyte antibodies has prompted major changes in the management of the blood supply in some countries; however, recent studies have suggested alternative pathophysiological mechanisms for TRALI related to the shelf life of cellular blood products. Although all blood products have been implicated, most reported cases were associated with fresh frozen plasma, red blood cell, and platelet transfusions. Because many patients have additional predisposing factors for acute lung injury, carefully designed prospective studies are needed to fully assess attributable risk related to transfusion. The treatment of TRALI is supportive, and the prognosis is generally better than for other causes of acute lung injury. As many as one third of all patients who develop acute lung injury have been exposed to blood products. TRALI may be an important and potentially preventable cause of acute lung injury. Transfusion-related acute lung injury (TRALI) is characterized by the sudden development of noncardiogenic pulmonary edema (acute lung injury) after transfusion of blood products. Poor awareness of TRALI outside of the blood transfusion medicine community has led to a serious underestimation of this condition, currently the most important severe complication of blood transfusion. Concern for the transfer of donor antileukocyte antibodies has prompted major changes in the management of the blood supply in some countries; however, recent studies have suggested alternative pathophysiological mechanisms for TRALI related to the shelf life of cellular blood products. Although all blood products have been implicated, most reported cases were associated with fresh frozen plasma, red blood cell, and platelet transfusions. Because many patients have additional predisposing factors for acute lung injury, carefully designed prospective studies are needed to fully assess attributable risk related to transfusion. The treatment of TRALI is supportive, and the prognosis is generally better than for other causes of acute lung injury. As many as one third of all patients who develop acute lung injury have been exposed to blood products. TRALI may be an important and potentially preventable cause of acute lung injury. With the substantial decrease in the transmission of viral pathogens by blood transfusions during the past decade, transfusion-related acute lung injury (TRALI) has emerged as the most common serious complication of blood transfusion. A lack of awareness of TRALI outside of the transfusion medicine community has led to serious underestimation of this important complication. In some countries, concern for the transfer of donor antileukocyte antibodies has prompted major changes in blood supply management, such as exclusion of women donors in the production of fresh frozen plasma (FFP) in the United Kingdom. Recent studies have suggested alternative pathophysiological mechanisms for TRALI related to the shelf life of cellular blood products. However, for the past 2 decades, most articles about this subject have been published almost exclusively in transfusion medicine subspecialty journals, contributing to a limited awareness of TRALI among general internists and critical care practitioners. We searched the National Library of Medicine PubMed database (www.pubmed.gov) from 1980 onward using the following search strategy: blood transfusion AND (acute lung injury OR adult respiratory distress syndrome OR pulmonary edema). Cohort and case-control studies, case series, case reports, animal models, and review articles were screened for relevant data regarding epidemiology, pathogenesis, diagnosis, treatment, and prevention of TRALI. Also, we looked up the references of selected articles and consulted experts for additional published or unpublished reports. The objectives of this review are as follows: (1) to review existing data regarding the incidence, clinical presentation, and outcome of TRALI; (2) to review the latest evidence regarding the 2 leading hypotheses for TRALI pathogenesis: (a) antibody-mediated lung injury associated with passive transfer of donor antileukocyte antibodies and (b) neutrophil-priming activity of biologically active lipid molecules accumulated during storage of cellular blood products; and (3) to propose a hypothesis that TRALI, similar to ventilator-associated lung injury, may be an important and frequently neglected cause of iatrogenic acute lung injury. Since the publication of our first case series 20 years ago,1Popovsky MA Moore SB Diagnostic and pathogenetic considerations in transfusion-related acute lung injury.Transfusion. 1985; 25: 573-577Crossref PubMed Scopus (653) Google Scholar TRALI has emerged as one of the most common serious complications of blood transfusion.2Popovsky MA Abel MD Moore SB Transfusion-related acute lung injury associated with passive transfer of antileukocyte antibodies.Am Rev Respir Dis. 1983; 128: 185-189Crossref PubMed Scopus (303) Google Scholar, 3Williamson LM Lowe S Love EM et al.Serious hazards of transfusion (SHOT) initiative: analysis of the first two annual reports.BMJ. 1999; 319: 16-19Crossref PubMed Scopus (289) Google Scholar, 4Popovsky MA Transfusion and lung injury.Transfus Clin Biol. 2001; 8: 272-277Crossref PubMed Scopus (86) Google Scholar, 5Kopko PM Holland PV Transfusion-related acute lung injury.Br J Haematol. 1999; 105: 322-329Crossref PubMed Scopus (132) Google Scholar With the reduction of clerical errors and with more effective screening and prevention of the transmission of infectious agents, TRALI has surpassed hemolytic reactions as the leading cause of transfusion-related mortality in developed countries.3Williamson LM Lowe S Love EM et al.Serious hazards of transfusion (SHOT) initiative: analysis of the first two annual reports.BMJ. 1999; 319: 16-19Crossref PubMed Scopus (289) Google Scholar, 6Zoon KC Transfusion related acute lung injury [letter]. US Dept of Health and Human Services, Center for Biologics Evaluation and Research, Rockville, Md2001Google Scholar Published incidence of TRALI ranged from 0.02% to 0.05% per blood product unit transfused and from 0.08% to 0.16% per patient who received a transfusion.1Popovsky MA Moore SB Diagnostic and pathogenetic considerations in transfusion-related acute lung injury.Transfusion. 1985; 25: 573-577Crossref PubMed Scopus (653) Google Scholar, 7Snyder EL Transfusion reactions.in: Hoffman R Benz Jr, EJ Shattil SJ Furie B Cohen HJ Silberstein LE Hematology: Basic Principles and Practice. 2nd ed. Churchill Livingstone, New York, NY1995: 2045-2053Google Scholar, 8Silliman CC Boshkov LK Mehdizadehkashi Z et al.Transfusion-related acute lung injury: epidemiology and a prospective analysis of etiologic factors.Blood. 2003; 101: 454-462Crossref PubMed Scopus (517) Google Scholar, 9Wallis JP Lubenko A Wells AW Chapman CE Single hospital experience of TRALI.Transfusion. 2003; 43: 1053-1059Crossref PubMed Scopus (134) Google Scholar, 10Ausley Jr, MB Fatal transfusion reactions caused by donor antibodies to recipient leukocytes.Am J Forensic Med Pathol. 1987; 8: 287-290Crossref PubMed Scopus (29) Google Scholar In contrast, the incidence of infectious complications varied from 1 in 20,000 blood product units for hepatitis B virus11Dodd RY Current safety of the blood supply in the United States.Int J Hematol. 2004; 80: 301-305Crossref PubMed Scopus (42) Google Scholar to 1 in 2 million blood product units for human immunodeficiency virus and hepatitis C virus.12Goodman JL The safety and availability of blood and tissues—progress and challenges [editorial].N Engl J Med. 2004; 351: 819-822Crossref PubMed Scopus (24) Google Scholar Although all plasmacontaining blood products have been implicated, use of FFP, red blood cells (RBCs), and pooled platelets from several donors seems to have a particularly high risk.1Popovsky MA Moore SB Diagnostic and pathogenetic considerations in transfusion-related acute lung injury.Transfusion. 1985; 25: 573-577Crossref PubMed Scopus (653) Google Scholar, 8Silliman CC Boshkov LK Mehdizadehkashi Z et al.Transfusion-related acute lung injury: epidemiology and a prospective analysis of etiologic factors.Blood. 2003; 101: 454-462Crossref PubMed Scopus (517) Google Scholar, 13Engelfriet CP Reesink HW Brand A et al.Transfusion-related acute lung injury (TRALI).Vox Sang. 2001; 81: 269-283Crossref PubMed Google Scholar, 14Kopko PM Marshall CS MacKenzie MR Holland PV Popovsky MA Transfusion-related acute lung injury: report of a clinical look-back investigation.JAMA. 2002; 287: 1968-1971Crossref PubMed Scopus (378) Google Scholar, 15Gajic O Rana R Mendez JL et al.Acute lung injury after blood transfusion in mechanically ventilated patients.Transfusion. 2004; 44: 1468-1474Crossref PubMed Scopus (116) Google Scholar Rarely, cryoprecipitate, intravenous immunoglobulin, and stem cell preparations have been implicated.16Webert KE Blajchman MA Transfusion-related acute lung injury.Transfus Med Rev. 2003; 17: 252-262Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar, 17Reese Jr, EP McCullough JJ Craddock PR An adverse pulmonary reaction to cryoprecipitate in a hemophiliac.Transfusion. 1975; 15: 583-588Crossref PubMed Scopus (47) Google Scholar, 18Suassuna JH da Costa MA Faria RA Melichar AC Noncardiogenic pulmonary edema triggered by intravenous immunoglobulin in cancer-associated thrombotic thrombocytopenic purpura-hemolytic uremic syndrome [letter].Nephron. 1997; 77: 368-370Crossref PubMed Scopus (23) Google Scholar In our original case series,1Popovsky MA Moore SB Diagnostic and pathogenetic considerations in transfusion-related acute lung injury.Transfusion. 1985; 25: 573-577Crossref PubMed Scopus (653) Google Scholar 31 of 36 patients received blood transfusion products in the perioperative period. In most cases, RBC and FFP transfusions were implicated, with antileukocyte antibodies present in 89% of the donor blood products.1Popovsky MA Moore SB Diagnostic and pathogenetic considerations in transfusion-related acute lung injury.Transfusion. 1985; 25: 573-577Crossref PubMed Scopus (653) Google Scholar In a recent retrospective review of 58 TRALI fatalities during a 5-year period, cardiopulmonary and hematologic disorders were the most common underlying diagnoses.19Holness L Knippen MA Simmons L Lachenbruch PA Fatalities caused by TRALI.Transfus Med Rev. 2004; 18: 184-188Abstract Full Text Full Text PDF PubMed Scopus (283) Google Scholar The most common associated blood product was FFP, implicated in 50% of cases.19Holness L Knippen MA Simmons L Lachenbruch PA Fatalities caused by TRALI.Transfus Med Rev. 2004; 18: 184-188Abstract Full Text Full Text PDF PubMed Scopus (283) Google Scholar In contrast, Silliman et al8Silliman CC Boshkov LK Mehdizadehkashi Z et al.Transfusion-related acute lung injury: epidemiology and a prospective analysis of etiologic factors.Blood. 2003; 101: 454-462Crossref PubMed Scopus (517) Google Scholar found that FFP was implicated in only 1 of 90 cases of TRALI during a 4-year period. Because of a relative lack of awareness, TRALI almost certainly is underdiagnosed and underreported.3Williamson LM Lowe S Love EM et al.Serious hazards of transfusion (SHOT) initiative: analysis of the first two annual reports.BMJ. 1999; 319: 16-19Crossref PubMed Scopus (289) Google Scholar, 14Kopko PM Marshall CS MacKenzie MR Holland PV Popovsky MA Transfusion-related acute lung injury: report of a clinical look-back investigation.JAMA. 2002; 287: 1968-1971Crossref PubMed Scopus (378) Google Scholar, 20Wallis JP Transfusion-related acute lung injury (TRALI)—under-diagnosed and under-reported [editorial].Br J Anaesth. 2003; 90: 573-576Crossref PubMed Scopus (123) Google Scholar, 21Popovsky MA Chaplin Jr, HC Moore SB Transfusion-related acute lung injury: a neglected, serious complication of hemotherapy.Transfusion. 1992; 32: 589-592Crossref PubMed Scopus (208) Google Scholar A recent “look-back study,” requested by the US Food and Drug Administration in response to a fatal TRALI reaction, revealed that 8 additional patients had developed severe acute lung injury after receiving blood donated by the same multiparous donor.14Kopko PM Marshall CS MacKenzie MR Holland PV Popovsky MA Transfusion-related acute lung injury: report of a clinical look-back investigation.JAMA. 2002; 287: 1968-1971Crossref PubMed Scopus (378) Google Scholar Interestingly, TRALI was considered in the differential diagnosis in only 2 of the 8 patients at the time of disease onset. Moreover, in a randomized clinical trial of critically ill patients, a restrictive transfusion threshold (hemoglobin at 7 g/dL vs traditional 10 g/dL) was associated with a decreased incidence of acute lung injury (7.7% vs 11.4%), suggesting that some episodes of acute lung injury may have been TRALI reactions.22Hebert PC Blajchman MA Cook DJ Transfusion Requirements in Critical Care Investigators for the Canadian Critical Care Trials Group et al.Do blood transfusions improve outcomes related to mechanical ventilation?.Chest. 2001; 119: 1850-1857Crossref PubMed Scopus (124) Google Scholar, 23Hebert PC Wells G Blajchman MA Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group et al.A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care [published correction appears in N Engl J Med. 1999;340:1056].N Engl J Med. 1999; 340: 409-417Crossref PubMed Scopus (4048) Google Scholar As many as one third of the 150,000 patients who develop acute lung injury in the United States each year are exposed to multiple blood products near the time of disease onset.24Hudson LD Milberg JA Anardi D Maunder RJ Clinical risks for development of the acute respiratory distress syndrome.Am J Respir Crit Care Med. 1995; 151: 293-301Crossref PubMed Scopus (790) Google Scholar, 25Goss CH Brower RG Hudson LD Rubenfeld GD ARDS Network Incidence of acute lung injury in the United States.Crit Care Med. 2003; 31: 1607-1611Crossref PubMed Scopus (279) Google Scholar It is unknown whether this association is causal or merely reflects the severity of the underlying illnesses. It is possible and even probable that current cases of TRALI reported to blood banks represent the “tip of the iceberg” and that transfusion factors play a mechanistic role in many more cases of acute lung injury than previously believed. Although several studies reported the association between blood transfusions and the development of acute lung injury in critically ill patients,22Hebert PC Blajchman MA Cook DJ Transfusion Requirements in Critical Care Investigators for the Canadian Critical Care Trials Group et al.Do blood transfusions improve outcomes related to mechanical ventilation?.Chest. 2001; 119: 1850-1857Crossref PubMed Scopus (124) Google Scholar, 24Hudson LD Milberg JA Anardi D Maunder RJ Clinical risks for development of the acute respiratory distress syndrome.Am J Respir Crit Care Med. 1995; 151: 293-301Crossref PubMed Scopus (790) Google Scholar, 26Pepe PE Potkin RT Reus DH Hudson LD Carrico CJ Clinical predictors of the adult respiratory distress syndrome.Am J Surg. 1982; 144: 124-130Abstract Full Text PDF PubMed Scopus (499) Google Scholar, 27Gajic O Dara SI Mendez JL et al.Ventilator-associated lung injury in patients without acute lung injury at the onset of mechanical ventilation.Crit Care Med. 2004; 32: 1817-1824Crossref PubMed Scopus (585) Google Scholar until recently the practice of transfusion usually was not characterized in terms of the amount, type, and shelf age of blood products. In a retrospectively studied cohort of patients receiving mechanical ventilation, transfusion of blood products and ventilator settings were identified as major risk factors for the subsequent development of acute lung injury, regardless of underlying severity of illness.27Gajic O Dara SI Mendez JL et al.Ventilator-associated lung injury in patients without acute lung injury at the onset of mechanical ventilation.Crit Care Med. 2004; 32: 1817-1824Crossref PubMed Scopus (585) Google Scholar To further characterize the specific factors associated with blood transfusion as risk factors for acute lung injury, we evaluated a subgroup of 181 critically ill patients who had received blood transfusion within 48 hours of receiving mechanical ventilation. One third of patients in the subgroup developed acute lung injury within 24 hours of receiving transfusion. Underlying thrombocytopenia and transfusion of FFP but not shelf age of stored RBCs or total number of transfusions were associated significantly with the development of acute lung injury in this patient population.15Gajic O Rana R Mendez JL et al.Acute lung injury after blood transfusion in mechanically ventilated patients.Transfusion. 2004; 44: 1468-1474Crossref PubMed Scopus (116) Google Scholar Our observations confirmed that critically ill patients have a high incidence of acute lung injury temporally related to the transfusion of blood products.24Hudson LD Milberg JA Anardi D Maunder RJ Clinical risks for development of the acute respiratory distress syndrome.Am J Respir Crit Care Med. 1995; 151: 293-301Crossref PubMed Scopus (790) Google Scholar The exact etiology of TRALI is unknown, but 2 distinct mechanisms have been suggested. The traditional theory proposes an antibody-mediated reaction between recipient granulocytes and antigranulocyte antibodies from donors who were sensitized during pregnancy (multiparous women) or by previous transfusion.2Popovsky MA Abel MD Moore SB Transfusion-related acute lung injury associated with passive transfer of antileukocyte antibodies.Am Rev Respir Dis. 1983; 128: 185-189Crossref PubMed Scopus (303) Google Scholar, 14Kopko PM Marshall CS MacKenzie MR Holland PV Popovsky MA Transfusion-related acute lung injury: report of a clinical look-back investigation.JAMA. 2002; 287: 1968-1971Crossref PubMed Scopus (378) Google Scholar, 28Palfi M Berg S Ernerudh J Berlin G A randomized controlled trial of transfusion-related acute lung injury: is plasma from multiparous blood donors dangerous?.Transfusion. 2001; 41: 317-322Crossref PubMed Scopus (191) Google Scholar, 29Seeger W Schneider U Kreusler B et al.Reproduction of transfusion-related acute lung injury in an ex vivo lung model.Blood. 1990; 76: 1438-1444PubMed Google Scholar In the original case series at our institution, antileukocyte antibodies were present in 89% of implicated donor products.1Popovsky MA Moore SB Diagnostic and pathogenetic considerations in transfusion-related acute lung injury.Transfusion. 1985; 25: 573-577Crossref PubMed Scopus (653) Google Scholar The antibody-mediated increase in pulmonary capillary permeability was reproduced in an ex vivo animal lung model of TRALI.29Seeger W Schneider U Kreusler B et al.Reproduction of transfusion-related acute lung injury in an ex vivo lung model.Blood. 1990; 76: 1438-1444PubMed Google Scholar Although most TRALI cases were associated with the presence of antileukocyte antibodies in the donor product, a few reports implicated the reaction between the recipient antileukocyte antibodies and donor leukocytes or interdonor incompatibility30Eastlund DT McGrath PC Burkart P Platelet transfusion reaction associated with interdonor HLA incompatibility.Vox Sang. 1988; 55: 157-160Crossref PubMed Scopus (28) Google Scholar, 31Bux J Becker F Seeger W Kilpatrick D Chapman J Waters A Transfusion-related acute lung injury due to HLA-A2-specific antibodies in recipient and NB1-specific antibodies in donor blood.Br J Haematol. 1996; 93: 707-713Crossref PubMed Scopus (146) Google Scholar; these 2 reactions are unlikely to play an important role in the future, given the rapid movement toward universal leukoreduction. Recently, an alternative mechanism was suggested, implicating proinflammatory molecules, predominantly lipid products of cell degradation, known to accumulate during storage of cellular blood product.8Silliman CC Boshkov LK Mehdizadehkashi Z et al.Transfusion-related acute lung injury: epidemiology and a prospective analysis of etiologic factors.Blood. 2003; 101: 454-462Crossref PubMed Scopus (517) Google Scholar, 32Silliman CC Voelkel NF Allard JD et al.Plasma and lipids from stored packed red blood cells cause acute lung injury in an animal model.J Clin Invest. 1998; 101: 1458-1467Crossref PubMed Google Scholar, 33Purdy FR Tweeddale MG Merrick PM Association of mortality with age of blood transfused in septic ICU patients.Can J Anaesth. 1997; 44: 1256-1261Crossref PubMed Scopus (313) Google Scholar, 34Geelhoed GW Bennett SH “Shock lung” resulting from perfusion of canine lungs with stored bank blood.Am Surg. 1975; 41: 661-682PubMed Google Scholar This hypothesis was tested in a lipopolysaccharide-primed perfused lung model in which the infusion of biologically active mediators from stored blood resulted in the development of permeability pulmonary edema.32Silliman CC Voelkel NF Allard JD et al.Plasma and lipids from stored packed red blood cells cause acute lung injury in an animal model.J Clin Invest. 1998; 101: 1458-1467Crossref PubMed Google Scholar Of note, the 2 hypotheses of TRALI pathogenesis (Figure 1) are not mutually exclusive and even may act synergistically with underlying patient factors to produce acute lung injury. In either theoretical model, an initial “priming” event (first hit) such as sepsis- or trauma-induced endothelial activation usually is required.1Popovsky MA Moore SB Diagnostic and pathogenetic considerations in transfusion-related acute lung injury.Transfusion. 1985; 25: 573-577Crossref PubMed Scopus (653) Google Scholar, 13Engelfriet CP Reesink HW Brand A et al.Transfusion-related acute lung injury (TRALI).Vox Sang. 2001; 81: 269-283Crossref PubMed Google Scholar, 29Seeger W Schneider U Kreusler B et al.Reproduction of transfusion-related acute lung injury in an ex vivo lung model.Blood. 1990; 76: 1438-1444PubMed Google Scholar, 30Eastlund DT McGrath PC Burkart P Platelet transfusion reaction associated with interdonor HLA incompatibility.Vox Sang. 1988; 55: 157-160Crossref PubMed Scopus (28) Google Scholar, 35Matthay MA Zimmerman GA Esmon C et al.Future research directions in acute lung injury: summary of a National Heart, Lung, and Blood Institute working group.Am J Respir Crit Care Med. 2003; 167: 1027-1035Crossref PubMed Scopus (467) Google Scholar In the largest clinical series to date, Silliman et al8Silliman CC Boshkov LK Mehdizadehkashi Z et al.Transfusion-related acute lung injury: epidemiology and a prospective analysis of etiologic factors.Blood. 2003; 101: 454-462Crossref PubMed Scopus (517) Google Scholar described 90 patients with TRALI treated at the transfusion medicine service at the University of Alberta Hospitals over a 4-year period. Compared with 225 randomly selected controls who received transfusions during the same period, patients with TRALI were more likely to have underlying cardiac disease or hematologic malignancy. The authors evaluated the presence of HLA class I and antigranulocyte antibodies in the donor blood of 28 patients with TRALI and 5 controls and found no significant difference. They described an elevated “neutrophil-priming” activity in the donor blood of patients with TRALI, which increased with the duration of platelet storage. Anti-HLA class II antibodies, interleukin (IL) 6, and IL-8 were measured in patients with TRALI but not in controls. In contrast to previous reports,1Popovsky MA Moore SB Diagnostic and pathogenetic considerations in transfusion-related acute lung injury.Transfusion. 1985; 25: 573-577Crossref PubMed Scopus (653) Google Scholar, 9Wallis JP Lubenko A Wells AW Chapman CE Single hospital experience of TRALI.Transfusion. 2003; 43: 1053-1059Crossref PubMed Scopus (134) Google Scholar, 13Engelfriet CP Reesink HW Brand A et al.Transfusion-related acute lung injury (TRALI).Vox Sang. 2001; 81: 269-283Crossref PubMed Google Scholar, 14Kopko PM Marshall CS MacKenzie MR Holland PV Popovsky MA Transfusion-related acute lung injury: report of a clinical look-back investigation.JAMA. 2002; 287: 1968-1971Crossref PubMed Scopus (378) Google Scholar, 15Gajic O Rana R Mendez JL et al.Acute lung injury after blood transfusion in mechanically ventilated patients.Transfusion. 2004; 44: 1468-1474Crossref PubMed Scopus (116) Google Scholar FFP was implicated in only 1 of 90 TRALI reactions. Moreover, donor antileukocyte antibodies were found in less than 25% of patients compared with 89% in the original series at our institution.1Popovsky MA Moore SB Diagnostic and pathogenetic considerations in transfusion-related acute lung injury.Transfusion. 1985; 25: 573-577Crossref PubMed Scopus (653) Google Scholar Differences in rates of TRALI after FFP transfusion are poorly understood and are likely related to different diagnostic criteria (clinical vs laboratory), varying antibody prevalence in the donor population, and variability in use of FFP in different patient populations. The duration of blood storage as a risk factor for adverse outcome has been assessed in several human studies with controversial results.15Gajic O Rana R Mendez JL et al.Acute lung injury after blood transfusion in mechanically ventilated patients.Transfusion. 2004; 44: 1468-1474Crossref PubMed Scopus (116) Google Scholar, 31Bux J Becker F Seeger W Kilpatrick D Chapman J Waters A Transfusion-related acute lung injury due to HLA-A2-specific antibodies in recipient and NB1-specific antibodies in donor blood.Br J Haematol. 1996; 93: 707-713Crossref PubMed Scopus (146) Google Scholar, 36Zallen G Offner PJ Moore EE 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 (448) Google Scholar, 37Walsh TS McArdle F McLellan SA 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; 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44: 1468-1474Crossref PubMed Scopus (116) Google Scholar The effect of platelet storage has been difficult to assess, primarily because of the short “shelf life” of platelets; most units are transfused near the end of a brief (5-day) storage period.8Silliman CC Boshkov LK Mehdizadehkashi Z et al.Transfusion-related acute lung injury: epidemiology and a prospective analysis of etiologic factors.Blood. 2003; 101: 454-462Crossref PubMed Scopus (517) Google Scholar, 15Gajic O Rana R Mendez JL et al.Acute lung injury after blood transfusion in mechanically ventilated patients.Transfusion. 2004; 44: 1468-1474Crossref PubMed Scopus (116) Google Scholar However, inflammatory cytokines are known to accumulate during both platelet (IL-6, tumor necrosis factor [TNF] a, IL-8) and RBC storage (IL-8, TNF-a).8Silliman CC Boshkov LK Mehdizadehkashi Z et al.Transfusion-related acute lung injury: epidemiology and a prospective analysis of etiologic factors.Blood. 2003; 101: 454-462Crossref PubMed Scopus (517) Google Scholar, 40Heddle NM Klama L Singer J et al.The role of the plasma from platelet concentrates in transfusion reactions.N Engl J Med. 1994; 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289: 1941-1949Crossref PubMed Scopus (297) Google Scholar Neither leukoreduction nor shorter storage would influence passive transfer of donor antileukocyte antibodies. The association between exposure to antileukocyte antibodies and TRALI reactions described in our original case series1Popovsky MA Moore SB Diagnostic and pathogenetic considerations in transfusion-related acute lung injury.Transfusion. 1985; 25: 573-577Crossref PubMed Scopus (653) Google Scholar was strengthened recently. In a small randomized trial, blood transfusion from only multiparous women donors produced impaired pulmonary gas exchange, increased plasma concentrations of inflammatory cytokines (TNF-a), and led to one severe and several mild TRALIlike reactions.28Palfi M Berg S Ernerudh J Berlin G A randomized controlled trial of transfusion-related acute lung injury: is plasma from multiparous blood donors dangerous?.Transfusion. 2001; 41: 317-322Crossref PubMed Scopus (191) Google Scholar Because no previous TRALI study has used a standardized definition of acute lung injury, interpreting results across different studies is difficult. Making a distinction between acute lung injury and related conditions such as hydrostatic pulmonary edema (fluid overload and cardiac failure) and lung infection is difficult because of the low specificity of diagnostic criteria.44Bernard GR Artigas A Brigham KL et al.The American-European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination.Am J Respir Crit Care Med. 1994; 149: 818-824Crossref PubMed Scopus (5301) Google Scholar, 45Abraham E Matthay MA Dinarello CA et al.Consensus conference definitions for sepsis, septic shock, acute lung injury, and acute respiratory distress syndrome: time for a reevaluation.Crit Care Med. 2000; 28: 232-235Crossref PubMed Scopus (304) Google Scholar, 46Meade MO Guyatt GH Cook RJ et al.Agreement between alternative classifications of acute respiratory distress syndrome.Am J Respir Crit Care Med. 2001; 163: 490-493Crossref PubMed Scopus (67) Google Scholar Furthermore, infection, pulmonary venous hypertension, and immune-mediated impairments in pulmonary vascular barrier function are not mutually exclusive. Application of the American-European Consensus Conference (AECC) definition44Bernard GR Artigas A Brigham KL et al.The American-European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination.Am J Respir Crit Care Med. 1994; 149: 818-824Crossref PubMed Scopus (5301) Google Scholar has substantially improved the validity of clinical studies of acute lung injury.47Acute Respiratory Distress Syndrome Network Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.N Engl J Med. 2000; 342: 1301-1308Crossref PubMed Scopus (10087) Google Scholar Recent inclusion of AECC criteria in the TRALI definition will help standardize future clinical studies.48Toy P Gajic O Transfusion-related acute lung injury.Anesth Analg. 2004; 99: 1623-1624Crossref PubMed Scopus (35) Google Scholar Symptoms of TRALI appear usually within 2 to 6 hours from initiation of transfusion, but cases of presumed TRALI have been described up to 48 hours after transfusion.5Kopko PM Holland PV Transfusion-related acute lung injury.Br J Haematol. 1999; 105: 322-329Crossref PubMed Scopus (132) Google Scholar, 49Levy GJ Shabot MM Hart ME Mya WW Goldfinger D Transfusion-associated noncardiogenic pulmonary edema: report of a case and a warning regarding treatment.Transfusion. 1986; 26: 278-281Crossref PubMed Scopus (72) Google Scholar Signs and symptoms of TRALI include dyspnea, tachypnea, frothy sputum, fever, hypotension, or, much more rarely, hypertension.48Toy P Gajic O Transfusion-related acute lung injury.Anesth Analg. 2004; 99: 1623-1624Crossref PubMed Scopus (35) Google Scholar Although application of the AECC definition44Bernard GR Artigas A Brigham KL et al.The American-European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination.Am J Respir Crit Care Med. 1994; 149: 818-824Crossref PubMed Scopus (5301) Google Scholar can help differentiate noncardiogenic from cardiogenic pulmonary edema and fluid overload, distinguishing TRALI solely on clinical grounds from other causes of acute lung injury such as sepsis, trauma, aspiration, disseminated intravascular coagulation, or ventilator-associated lung injury is almost impossible. Laboratory findings for TRALI are inconsistent and include acute transient neutropenia,50Yomtovian R Kline W Press C et al.Severe pulmonary hypersensitivity associated with passive transfusion of a neutrophil-specific antibody.Lancet. 1984; 1: 244-246Abstract PubMed Scopus (138) Google Scholar the presence of matching leukocyte antigen-antibody in the donor and recipient, donor antibody that activates recipient monocytes,51Kopko PM Paglieroni TG Popovsky MA Muto KN MacKenzie MR Holland PV TRALI: correlation of antigen-antibody and monocyte activation in donor-recipient pairs.Transfusion. 2003; 43: 177-184Crossref PubMed Scopus (162) Google Scholar and increased neutrophil-priming activity in transfused blood.8Silliman CC Boshkov LK Mehdizadehkashi Z et al.Transfusion-related acute lung injury: epidemiology and a prospective analysis of etiologic factors.Blood. 2003; 101: 454-462Crossref PubMed Scopus (517) Google Scholar In patients with an endotracheal tube in place, high protein concentration found in edema fluid sampled within the first hour of intubation may help differentiate TRALI from fluid overload and cardiogenic pulmonary edema.52Looney MR Gropper MA Matthay MA Transfusion-related acute lung injury: a review.Chest. 2004; 126: 249-258Crossref PubMed Scopus (196) Google Scholar There is no single test for TRALI; thus, diagnosis is problematic and requires a high index of clinical suspicion. Unfortunately, most cases remain unnoticed or misdiagnosed as fluid overload or acute lung injury of other etiology.2Popovsky MA Abel MD Moore SB Transfusion-related acute lung injury associated with passive transfer of antileukocyte antibodies.Am Rev Respir Dis. 1983; 128: 185-189Crossref PubMed Scopus (303) Google Scholar, 14Kopko PM Marshall CS MacKenzie MR Holland PV Popovsky MA Transfusion-related acute lung injury: report of a clinical look-back investigation.JAMA. 2002; 287: 1968-1971Crossref PubMed Scopus (378) Google Scholar, 21Popovsky MA Chaplin Jr, HC Moore SB Transfusion-related acute lung injury: a neglected, serious complication of hemotherapy.Transfusion. 1992; 32: 589-592Crossref PubMed Scopus (208) Google Scholar In the previously mentioned look-back study,14Kopko PM Marshall CS MacKenzie MR Holland PV Popovsky MA Transfusion-related acute lung injury: report of a clinical look-back investigation.JAMA. 2002; 287: 1968-1971Crossref PubMed Scopus (378) Google Scholar TRALI was considered in the differential diagnosis in only 2 of 8 patients at the time of disease onset. TRALI is believed to have a better short-term prognosis than other causes of acute lung injury; less than 70% of patients with TRALI require mechanical ventilation, and hospital mortality is 5% to 15%.1Popovsky MA Moore SB Diagnostic and pathogenetic considerations in transfusion-related acute lung injury.Transfusion. 1985; 25: 573-577Crossref PubMed Scopus (653) Google Scholar, 4Popovsky MA Transfusion and lung injury.Transfus Clin Biol. 2001; 8: 272-277Crossref PubMed Scopus (86) Google Scholar, 8Silliman CC Boshkov LK Mehdizadehkashi Z et al.Transfusion-related acute lung injury: epidemiology and a prospective analysis of etiologic factors.Blood. 2003; 101: 454-462Crossref PubMed Scopus (517) Google Scholar, 9Wallis JP Lubenko A Wells AW Chapman CE Single hospital experience of TRALI.Transfusion. 2003; 43: 1053-1059Crossref PubMed Scopus (134) Google Scholar Most patients recover within 24 to 48 hours with supportive care. Although less clinically severe than some other causes of acute lung injury, TRALI is costly because patients need intensive care treatment for 2 to 7 days.4Popovsky MA Transfusion and lung injury.Transfus Clin Biol. 2001; 8: 272-277Crossref PubMed Scopus (86) Google Scholar, 7Snyder EL Transfusion reactions.in: Hoffman R Benz Jr, EJ Shattil SJ Furie B Cohen HJ Silberstein LE Hematology: Basic Principles and Practice. 2nd ed. Churchill Livingstone, New York, NY1995: 2045-2053Google Scholar Management of TRALI is supportive, as it is for any patient with permeability pulmonary edema, and often includes ventilatory support. Lung protective (low tidal volume) ventilatory strategies should be used. Unless there is concomitant fluid overload, diuretics are unlikely to be beneficial and even may be clinically contraindicated.48Toy P Gajic O Transfusion-related acute lung injury.Anesth Analg. 2004; 99: 1623-1624Crossref PubMed Scopus (35) Google Scholar Suspected TRALI reactions should be reported to the blood bank, and a transfusion reaction work-up should be initiated. In addition to acquiring a posttransfusion blood specimen from the patient, bags from units of blood transfused in the last 6 hours should be returned to the blood bank if possible so that residual donor plasma can be tested without necessitating a time-consuming recall of blood donors.48Toy P Gajic O Transfusion-related acute lung injury.Anesth Analg. 2004; 99: 1623-1624Crossref PubMed Scopus (35) Google Scholar Medical records should be reviewed to determine the sequence and timing of transfused units in relation to the clinical manifestations of the disease.48Toy P Gajic O Transfusion-related acute lung injury.Anesth Analg. 2004; 99: 1623-1624Crossref PubMed Scopus (35) Google Scholar Of note, as many as 25% of multiparous women have circulating antileukocyte antibodies, which also are found in approximately 5% of all plasma-containing blood products.53Densmore TL Goodnough LT Ali S Dynis M Chaplin H Prevalence of HLA sensitization in female apheresis donors.Transfusion. 1999; 39: 103-106Crossref PubMed Scopus (192) Google Scholar However, most recipients of these transfusion products do not develop TRALI.4Popovsky MA Transfusion and lung injury.Transfus Clin Biol. 2001; 8: 272-277Crossref PubMed Scopus (86) Google Scholar, 28Palfi M Berg S Ernerudh J Berlin G A randomized controlled trial of transfusion-related acute lung injury: is plasma from multiparous blood donors dangerous?.Transfusion. 2001; 41: 317-322Crossref PubMed Scopus (191) Google Scholar Currently in North America, neither routine exclusion of women donors in the production of FFP, as recently proposed in the United Kingdom,54England bans FFP from female donors to prevent TRALI.ABC Newslett. 2003; 44: 1-5Google Scholar nor changes in duration of storage are recommended.4Popovsky MA Transfusion and lung injury.Transfus Clin Biol. 2001; 8: 272-277Crossref PubMed Scopus (86) Google Scholar, 5Kopko PM Holland PV Transfusion-related acute lung injury.Br J Haematol. 1999; 105: 322-329Crossref PubMed Scopus (132) Google Scholar Considering the shortage of blood products, the public health implications are obvious if the efficacy of either of these practices is confirmed in a rigorous epidemiological study.5Kopko PM Holland PV Transfusion-related acute lung injury.Br J Haematol. 1999; 105: 322-329Crossref PubMed Scopus (132) Google Scholar Such a study should aim to answer the following fundamental questions: What is the incidence of clinically defined TRALI in a rigorously conducted prospective clinical study? Are antileukocyte antibodies, inflammatory cytokines, or biologically active lipids more likely to be present in the donor blood of patients with clinically defined TRALI compared with control patients matched for age, severity of illness, and number of blood transfusions? What are the most important underlying risk factors (first hit) that increase the probability of TRALI, and what patient population would thus likely benefit from clinical trials of specific interventions, such as washing of cellular products, pretransfusion antibody testing, or avoidance of a specific donor product? What are the short-term and long-term outcomes of TRALI? Transfusion is a relatively common and important risk factor for acute lung injury. Cases of TRALI reported to blood banks may represent just the tip of the iceberg, and transfusion may play a mechanistic role in many more cases of acute lung injury than currently realized. To the extent that acute lung injury is related to transfusion factors, it may be a preventable disease.
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