Recipients of blood from a donor with multiple HLA antibodies: a lookback study of transfusion-related acute lung injury

BACKGROUND: The effects of transfusion of HLA antibodies to patients with corresponding antigens are not well known. STUDY DESIGN AND METHODS: Records of patients who received blood from previous donations of a donor implicated in a case of transfusion-related acute lung injury (TRALI) were examined. The donor had multiple HLA antibodies reactive with 96 percent of HLA Class I antigens and 88 percent of HLA Class II antigens. RESULTS: Among 103 patients (40 with a pretransfusion white blood cell [WBC] count of >/=3.5 x 10(9)/L), 1 patient met criteria for TRALI and had clinical evidence for diffuse alveolar hemorrhage. Among the subset of 55 patients (17 with a pretransfusion WBC count of 3.5 x 10(9)/L) with known HLA types, none developed TRALI even though 54 (98%) had one to five corresponding HLA antigens. In a subgroup of patients four of 62 patients with chest radiographs, developed new or worse bilateral infiltrates with implicated but not control units (p = 0.0625). CONCLUSION: Transfusion of HLA antibodies from this donor to nonneutropenic patients did not cause TRALI, but there was a trend of an association with new or worse bilateral pulmonary infiltrates. Further research is needed to determine why transfusion of HLA antibodies to recipients with corresponding antigens causes TRALI in some cases and not in others.     

Proposed revised nomenclature for transfusion‐related acute lung injury

A decade ago, definitions of “transfusion?related acute lung injury (TRALI)” and “possible TRALI” were standardized for research and clinical diagnosis. Since then, evidence has confirmed that TRALI is often due to transfusion of white blood cell antibodies to at‐risk patients, and the term “TRALI, antibody mediated” is appropriate for such cases. Other TRALI cases are non–antibody mediated. Because specific, nonantibody transfusion factors have not yet been confirmed to cause TRALI in humans, the general term “TRALI, non–antibody mediated” is appropriate for such cases. In contrast, evidence is against possible TRALI being due to transfusion with the more likely cause of the acute respiratory distress syndrome (ARDS) being the alternative ARDS risk factor present in these patients. We propose to drop the misleading term “possible TRALI” and to rename this category of cases as “transfused ARDS.” These nomenclature updates will more accurately categorize ARDS cases that develop after transfusion.     

A moderate transfusion regimen may reduce iron loading in beta- thalassemia major without producing excessive expansion of erythropoiesis

BACKGROUND: Hypertransfusion with a baseline hemoglobin of 10 to 12 g per dL is still considered by many to be the mainstay of conservative therapy for beta-thalassemia major. However, this regimen is frequently associated with manifestations of transfusion iron overload, despite regular chelation therapy with subcutaneous desferoxamine. STUDY DESIGN AND METHODS: To verify whether a transfusion regimen with a target pretransfusion hemoglobin level between 9 and 10 g per dL can allow a significant reduction in blood consumption, while still effectively suppressing erythropoiesis, the records were reviewed of 32 beta- thalassemia major patients, who were maintained at a pretransfusion hemoglobin of 11.3 +/? 0.5 g per dL between 1981 and 1986. These patients were switched at the beginning of 1987 to a transfusion regimen with pretransfusion hemoglobin of 9.4 +/? 0.4 g per dL. The degree of erythroid marrow activity was evaluated in these patients and in 32 subjects with beta-thalassemia intermedia through the simple measurement of serum transferrin receptor. RESULTS: After the adoption of the moderate transfusion regimen, transfusion requirements decreased from 137 +/? 26 to 104 +/? 23 mL per kg per year of red cells (p < 0.0001), and mean serum ferritin decreased from 2448 +/? 1515 to 1187 +/? 816 micrograms per L (p < 0.0001), with one-half of patients achieving serum ferritin levels lower than 1000 micrograms per L. The proportion of patients having spontaneous pubertal development increased significantly (p < 0.01), as a result of less iron-related gonadotropin insufficiency. At the lower pretransfusion hemoglobin, erythroid marrow activity did not exceed two to three times normal levels in most subjects. CONCLUSION: As compared with hypertransfusion, moderate transfusion may allow more effective prevention of iron loading, with higher likelihood of spontaneous pubertal development and without producing excessive expansion of erythropoiesis.     

Recurrent transfusion-related acute lung injury

BACKGROUND: Transfusion-related acute lung injury (TRALI) is a rare condition that is commonly associated with the transfusion of donor plasma containing WBC antibodies. Biologically active lipids that accumulate during storage of RBCs and platelets may also cause TRALI. There has been only one previously reported case of recurrent TRALI. CASE REPORT: A patient received a transfusion 2 days after undergoing hysterectomy; she developed TRALI after receiving the transfusion. The patient recovered after being on ventilation for 6 days but received an additional transfusion and had a second episode of TRALI, which required further ventilation. RESULTS: Laboratory investigation of the first episode of TRALI suggested the presence of HLA-A2 (N = 1) and granulocyte-specific IgM antibodies (N = 2) in the sera from three of the donors. All three sera reacted in crossmatch studies with the patient's granulocytes and lymphocytes. Lymphocyte-specific IgG antibodies were detected in the patient's serum. There was no evidence to suggest the involvement of WBC antibodies in the second episode of TRALI. Antibody screening of the donors' samples and both forward and reverse crossmatch studies were negative. CONCLUSION: The first episode of TRALI seems to be due to the action of HLA-A2 and granulocyte-specific IgM antibodies. The second episode may have been due to the action of lipid neutrophil-priming agents in the donors' units in association with the patient's underlying pulmonary condition (i.e., recovering from lung injury). TRALI can recur if a patient requires further transfusion support shortly after an initial episode of TRALI.     

Phenotyping autologous red cells within 1 day after allogeneic blood transfusion by using immunomagnetic isolation of reticulocytes

BACKGROUND: When a transfused patient develops multiple or weak blood group antibodies, posttransfusion phenotyping is useful in antibody identification. To perform a correct phenotyping after transfusion, isolation of autologous red cells is necessary. However, mature autologous red cells are impossible to separate from their donor counterparts. Since the proportion of autologous reticulocytes compared to donor reticulocytes increases rapidly after transfusion, selective isolation of reticulocytes provides autologous cells for antigen typing. STUDY DESIGN AND METHODS: Extensive phenotyping was performed on red cells from 10 surgical patients before transfusion and on red cells and reticulocytes after the transfusion of 5 or more red cell units. Reticulocytes were isolated by using an antibody against the human transferrin receptor coupled to magnetic beads. RESULTS: The data showed nearly full agreement between pretransfusion phenotyping of red cells and posttransfusion typing of reticulocytes. Correct phenotyping of transferred patients could be obtained 8 to 10 hours after transfusion using isolated reticulocytes. CONCLUSION: This method is helpful in selecting compatible blood when patients have developed antibodies and have an urgent need for further transfusions.     

Pulmonary pathology of rapidly fatal transfusion-related acute lung injury reveals minimal evidence of diffuse alveolar damage or alveolar granulocyte infiltration

BACKGROUND: Transfusion‐related acute lung injury (TRALI) is the leading cause of transfusion‐associated death in the United States. Its diagnosis is based on clinical and radiographic changes that are indistinguishable from acute lung injury/acute respiratory distress syndrome (ALI/ARDS). TRALI is presumed to be a form of ALI/ARDS; however, it differs in its triggering events and associated mortality. Two cases of rapidly fatal TRALI in which the postmortem pathology differed from that classically associated with ALI/ARDS are reported. CASE REPORT: Two men (aged 75 and 83 years) developed rapidly fatal TRALI after receiving single units of plasma for correction of elevated international normalized ratios. The donors were found to have white blood cell (WBC) antibodies that included specificities for WBC antigens expressed by the recipient (HLA Class I or Class II and/or HNA‐3b [5a] antibody). Autopsy findings in both patients revealed bilateral pleural effusions and extensive patchy areas of alveoli filled with proteinaceous fluid. The pulmonary capillaries were congested with red blood cells and WBCs. Diffuse alveolar damage, including interstitial inflammation, intraalveolar granulocyte infiltration, and hyaline membrane formation, were not identified in either case. CONCLUSION: In both patients the clinical and radiographic findings were indicative of TRALI and indistinguishable from ALI/ARDS. However, diffuse alveolar damage, the classic autopsy finding in ARDS, was not identified, suggesting a different pathogenesis. Further studies are needed on the role of polymorphonuclear cells in the initiating events of TRALI that lead to ALI and the resulting breakdown of the permeability integrity of the alveolar walls.     

The practice of reporting transfusion‐related acute lung injury: a national survey among clinical and preclinical disciplines

BACKGROUND: Transfusion‐related acute lung injury (TRALI) is hypothesized to be a “two‐hit” entity, in which an inflammatory condition (e.g., sepsis) predisposes to TRALI. TRALI is a clinical diagnosis. Disciplines involved in managing TRALI may differ in decision‐making on the reporting of TRALI. STUDY DESIGN AND METHODS: A survey was conducted among critical care physicians, hematologists, hemovigilance workers, and transfusion medicine physicians, using case vignettes and a questionnaire. The vignettes varied in patient‐ and blood product–related factors that may influence the decision to report a TRALI case. Multiple linear regression analysis was performed. A positive β‐coefficient is in favor of reporting. RESULTS: Ninety‐two questionnaires were returned (response rate, 68%). For all disciplines, preferences in favor of reporting TRALI were onset of symptoms within 1 hour (β = 0.4), after transfusion of a single unit of FFP (β = 0.5), and in the absence of acute lung injury before transfusion (β = 1.3). An admission diagnosis of sepsis was a negative preference (β = ?0.3). Massive transfusion (6 RBC plus 4 FFP units) was a negative preference for transfusion medicine physicians (β = ?0.3), but a positive preference for the other disciplines. The questionnaire revealed that massive transfusion and the age of blood products were considered relatively more important reasons to report TRALI by critical care physicians compared to the other disciplines (p < 0.05). CONCLUSION: A pretransfusion inflammatory condition is a reason to withhold from reporting of a suspected TRALI case. Disciplines involved in managing TRALI differ in decision‐making of reporting TRALI, which may contribute to variance in incidence.     

Pathophysiology of TRALI: current concepts

Transfusion-related acute lung injury (TRALI) is a life-threatening adverse event in blood transfusion and is considered the most common cause of transfusion-related fatalities in the United States and the United Kingdom. TRALI and acute respiratory distress syndrome (ARDS) share a common clinical definition except that TRALI is temporally and mechanistically related to blood transfusion. Two different mechanisms have been proposed. The first is leuko-agglutination due to infusion of leukocyte Antibodies with the blood product transfused. The second proposes a two-event model where the first event is the clinical condition of the patient, and the second the infusion of lipids that accumulate in blood products during storage. An emerging common pathway of granulocyte activation is discussed, as is the relevance of immune and non-immune TRALI from a practical point of view. Some unresolved questions in TRALI pathophysiology, including the relevance of Antibodies to HLA class-II antigens and the participation of the endothelium, are examined, as are the suggested preventive measures for both immune and non-immune TRALI. It is concluded that further clinical and experimental data are necessary before any recommendations can be made regarding non-immune TRALI. In contrast, in immune TRALI, preventive measures to avoid transfusion of blood products that contain leukocyte Antibodies should be taken now.     

The transfusion of neutrophil-specific antibodies causes leukopenia and a broad spectrum of pulmonary reactions

BACKGROUND: Antibodies to neutrophil-specific antigens are the best characterized cause of transfusion-related acute lung injury (TRALI). CASE REPORT: A double-apheresis platelet (PLT) component was divided and transfused into two patients. One experienced chills, rigors, and dyspnea and the other experienced chills and headache. Transient leukopenia developed in both patients. RESULTS: Evaluation of donor plasma revealed an anti-HNA-2a and no HLA Class I antibodies. The donor had donated 26 previous apheresis PLT components. The 27 donations resulted in 39 separate transfusions and 12 transfusion reactions in 9 patients. Five reactions occurred immediately after the transfusion, 10 within 1 hour, and all within 2.5 hours. Nine of the reactions involved symptoms or signs of pulmonary dysfunction. The symptoms were mild to moderate in nature. None of the inpatients required intensive care transfer nor did any outpatients require hospital admission. Recipient white blood cell (WBC) counts were measured within 8 hours after 38 of 39 transfusions. Leukopenia occurred in 9 of 12 (75%) transfusions with reactions and in 9 of 26 (35%) transfusions without. The reactions did not correlate with pretransfusion WBC count. CONCLUSIONS: Neutrophil antibodies cause a wide variety of transfusion reactions that do not necessarily meet the definition of TRALI. Donors of blood products causing even mild pulmonary reactions or leukopenia should be tested for neutrophil-specific antibodies.     

Transfusion-related acute lung injury due to granulocyte-agglutinating antibody in a patient with paroxysmal nocturnal hemoglobinuria

BACKGROUND: Transfusion-related acute lung injury (TRALI) is usually reported after the transfusion of blood components from donors with white cell (WBC) antibodies, but only very rarely if the patient has these antibodies. The pathogenesis of TRALI is not fully understood. Not all transfusion recipients develop TRALI, even though WBC antibodies are present in the donor or the recipient. CASE REPORT: A patient with paroxysmal nocturnal hemoglobinuria (PNH) who developed TRALI after the transfusion of non-WBC-reduced red cells is described. Granulocyte-agglutinating anti-5b was detected in his serum, and the crossmatch with the donor granulocytes was positive. The patient also developed a severe exacerbation of hemolysis with renal failure; serologic results excluded an immune hemolytic posttransfusion reaction. The patient recovered from both events after about 1 week. CONCLUSION: Granulocyte-agglutinating antibodies present in the recipient play an important role in TRALI, and also other factors may contribute to its pathogenesis. The reaction between the PNH patient's antibody (anti-5b) and transfused WBCs was found not only to be responsible for the respiratory distress but also to have triggered, through the innocent-bystander mechanism of complement activation, an intensive hemolysis, which was very likely a contributing factor in the development of TRALI.     

The effect of transfusion on cardiac function in patients with chronic anemia

BACKGROUND: The deteriorating cardiac function of patients with chronic anemia may be improved with transfusion. The effect of transfusion on cardiac function was evaluated in patients with chronic anemia. STUDY DESIGN AND METHODS: In a prospective study, ejection fraction (EF) was determined before and after transfusion in 41 patients with chronic anemia. The results were compared and analyzed. RESULTS: The volume of red cells transfused and the levels of pretransfusion hemoglobin, hematocrit, and red cell, white cell, and platelet counts did not affect the posttransfusion EF, whereas the pretransfusion EF of the right or left ventricle inversely affected the posttransfusion change in EF in the respective ventricle (p < 0.001 and r = -0.5022; p = 0.01 and -0.3917, respectively). There was no significant difference in the change in EF in the right and left ventricles. CONCLUSION: Transfusion produced little immediate effect on cardiac function, but did change the EF to an extent that aided cardiac function in chronic anemia patients. The pretransfusion EF itself, but not the degree of anemia or volume of red cells transfused, affected the posttransfusion change in EF.     

A randomized controlled trial oftransfusion‐related acute lung injury: is plasma from multiparous blood donors dangerous?

BACKGROUND: Transfusion-related acute lung injury (TRALI) and other posttransfusion reactions may be caused by granulocyte and/or HLA antibodies, which are often present in blood from multiparous donors. The purpose of this study was to compare the effects of plasma from multiparous donors with those of plasma from donors with no history of transfusion or pregnancy (control plasma) in a prospective, randomized, double-blind, crossover study. STUDY DESIGN AND METHODS: Intensive care patients, judged to need at least 2 units of plasma, were randomly assigned to receive a unit of control plasma and, 4 hours later, a plasma unit from a multiparous donor (> or = 3 live births) or to receive the plasma units in opposite order. The patients were closely monitored, and body temperature, blood pressure, and heart rate were recorded. Blood samples for analysis of blood gases, TNFalpha, IL-1 receptor antagonist, soluble E selectin, and C3d complement factor were collected at least on four occasions (before and after the transfusion of each unit). RESULTS: Transfusion of plasma from multiparous donors was associated with significantly lower oxygen saturation and higher TNFalpha concentrations than transfusion of control plasma. The mean arterial pressure increased significantly after the transfusion of control plasma, whereas plasma from multiparous donors had no effect on it. Five posttransfusion reactions were observed in 100 patients, in four cases after the transfusion of plasma from multiparous donors. CONCLUSION: Plasma from multiparous blood donors may impair pulmonary function in intensive care unit patients.     

Redefining transfusion‐related acute lung injury: don't throw the baby out with the bathwater

Recently two articles have been published in TRANSFUSION in which the authors propose to change the current definition on transfusion‐related acute lung injury (TRALI). It was proposed to view TRALI from the perspective of detectability versus nondetectability of leukoreactive alloantibodies (Transfusion 2015;55:1128‐34). The authors argue that only cases in which leukoreactive alloantibodies can be detected should be defined as “true” TRALI in analogy with the understanding of the pathophysiology of heparin‐induced thrombocytopenia. In the other article (Transfusion 2015;55:947‐52), the authors propose to redefine possible TRALI to transfused acute respiratory distress syndrome (ARDS) as their study in intensive care unit patients did not show a relation between the number of transfusions and possible TRALI.We discuss these two propositions in light of the current evidence on pathophysiology of TRALI and possible TRALI. We argue that it is too early to redefine TRALI, as 1) factors, such as storage time of platelets, which induce TRALI in preclinical studies, have not yet been properly investigated in humans. Further research is needed on these agents before it is concluded that antibody‐mediated TRALI is the only “true” TRALI. 2) In light of the current knowledge, it makes perfect sense that multiple transfusion is not related to possible TRALI: ARDS risk factors in these patients result in a very sensitive equilibrium in which even only one transfusion induces TRALI. Excluding possible TRALI from the TRALI definition would result in further underrecognition of TRALI induced by alloantibodies and interferes with exclusion of donors related to TRALI cases and thus TRALI prevention.     

Pathophysiology of TRALI: current concepts

Transfusion-related acutelung injury (TRALI) is a life-threateningadverse event in blood transfusionand is considered the most common cause of transfusion-related fatalitiesin the United States and theUnited Kingdom. TRALI and acuterespiratory distress syndrome(ARDS) share a common clinicaldefinition except that TRALI is temporallyand mechanistically relatedto blood transfusion. Two differentmechanisms have been proposed.The first is leuko-agglutination dueto infusion of leukocyte Antibodieswith the blood product transfused.The second proposes a two-eventmodel where the first event is theclinical condition of the patient, andthe second the infusion of lipids thataccumulate in blood products duringstorage. An emerging common pathwayof granulocyte activation is discussed,as is the relevance of immuneand non-immune TRALI froma practical point of view. Some unresolvedquestions in TRALI pathophysiology,including the relevanceof Antibodies to HLA class-II antigensand the participation of the endothelium,are examined, as are thesuggested preventive measures forboth immune and non-immuneTRALI. It is concluded that furtherclinical and experimental data arenecessary before any recommendationscan be made regarding non-immuneTRALI. In contrast, in immuneTRALI, preventive measuresto avoid transfusion of blood productsthat contain leukocyte Antibodiesshould be taken now.     

Transfusion-transmissible viral infections among US military recipients of whole blood and platelets during Operation Enduring Freedom and Operation Iraqi Freedom

BACKGROUND: Current US military clinical practice guidelines permit emergency transfusions of non–Food and Drug Administration (FDA)‐compliant freshly collected blood products in theaters of war. This investigation aimed to characterize the risks of transfusion‐transmitted infections (TTIs) associated with battlefield transfusions of non–FDA‐compliant blood products. STUDY DESIGN AND METHODS: US Service members who received emergency transfusion products in Iraq and Afghanistan (March 1, 2002‐September 30, 2007) were tested for hepatitis C virus (HCV), human immunodeficiency virus (HIV), and hepatitis B virus (HBV) infections using reposed pre‐ and posttransfusion sera. Selected regions of viral genomes from epidemiologically linked infected recipients and their donors were sequenced and compared. RESULTS: Of 761 US Service members who received emergency transfusion products, 475 were tested for HCV, 472 for HIV, and 469 for HBV. One transfusion‐transmitted HCV infection (incidence rate of 2.1/1000 persons) was identified. The pretransfusion numbers (prevalence per 1000 persons) were HCV—four (8/1000), HIV—zero (0/1000), chronic HBV—two (4 /1000), and naturally immune (antibody to HBV core antigen)—nine (19/1000). CONCLUSION: One HCV TTI was determined to be associated with emergency blood product use. The pretransfusion HCV and HBV prevalence in transfusion recipients, themselves members of the potential donor population, indicates better characterization of the deployed force's actual donor population, and further investigations of the TTI prevalence in these donors are needed. These data will inform countermeasure development and clinical decision making.     

The evaluation of a positive direct antiglobulin test in pretransfusion testing

The results of serologic studies on 879 blood samples with a positive direct antiglobulin test (DAT) are presented. All blood samples were from patients who were either anemic, for reasons other than blood loss, recently transfused, or had serum antibodies detected during routine pretransfusion tests. Blood samples from only 81 of the patients included in this study had serologically reactive eluates (64 autoantibodies, three antibodies to penicillin and cephalothin treated red blood cells, three passively acquired anti-A antibodies, and 11 transfusion-induced alloantibodies). The eluted antibodies were also detected in the serum by routine pretransfusion tests in 13 of the patients whose red blood cells eluted autoantibodies, and in five of the patients whose red blood cells eluted transfusion-induced alloantibodies. All but one of the 11 transfusion-induced alloantibodies were detected within 14 days posttransfusion. Based on these findings, a cost-effective and safe approach to the management of blood samples with a positive DAT would be to restrict the preparation and testing of eluates to those samples from recently transfused patients. It is the contention of the authors that the incorporation of the DAT in pretransfusion testing should primarily serve to detect alloantibody formation before such antibodies are evident in the serum, and should not be used to screen patients for unsuspected autoimmune hemolytic anemia. Furthermore, the authors question the necessity for blood banks to routinely perform an autocontrol on all blood samples from prospective transfusion recipients.     

Platelet alloantibodies in transfused patients

BACKGROUND: Patients receiving cellular blood components may form HLA antibodies and platelet-specific alloantibodies. STUDY DESIGN AND METHODS: Serum samples from a cohort of 252 patients with hematologic or oncologic diseases who are receiving cellular blood components were studied for platelet-reactive antibodies. Specificity of platelet alloantibodies was determined with a panel of typed platelets RESULTS: Platelet-reactive antibodies were detected in the sera of 113 patients (44.8% of 252), HLA antibodies in the sera of 108 (42.9%), and platelet-specific antibodies in the sera of 20 (8%). The following platelet-specific antibodies were identified: anti-HPA-5b (n = 10), anti-HPA-1b (n = 4), anti-HPA-5a (n = 2), anti-HPA-1a (n = 1), anti-HPA-2b (n = 1), anti-HPA-1b+5b (n = 1), and anti-HPA-1b+2b (n = 1). Fifteen sera from the 108 patients with anti-HLA (13.9%) contained additional platelet-specific alloantibodies, while in 5 sera, platelet-specific alloantibodies only were detected: anti-HPA-5b (n = 4) and anti-HPA-1a (n = 1). Of the 108 sera with HLA antibodies, 29 (26.9%) showed discordant results when studied with the lymphocytotoxicity test and the glycoprotein-specific immunoassay. Ten sera contained panreactive antibodies against platelet glycoproteins (GP) IIb/IIIa, GPIa/IIa, and/or GPIb/IX. Alloimmunization occurred in 58.3 percent of female patients with previous pregnancies, but in only 23.3 percent of those without previous pregnancies (p = 0.0049). CONCLUSION: Platelet alloantibody specificities in transfused patients (predominantly anti-HPA-5b and -1b with antigen frequencies <30% among whites) differ significantly from those observed in patients with neonatal alloimmune thrombocytopenia or posttransfusion purpura, in whom anti-HPA-1a (antigen frequency >95%) is the most prevalent specificity. HLA antibody detection yields discordant results when the lymphocytotoxicity assay and a glycoprotein-specific immunoglobulin-binding assay are used.     

TRALI risk reduction: Donor and component management strategies

Transfusion‐related lung injury (TRALI) occurs in ～1 in 5,000 transfusions and may cause considerably more morbidity and mortality that is not recognized in clinical practice. Based on the current understanding of the etiology of TRALI, blood centers have implemented or are evaluating various donor and component management strategies in an effort to mitigate the risk of TRALI. Many cases of TRALI are likely caused by antibodies to leukocyte antigens (HLA or HNA) in blood components. Approximately 10 to 20% of female blood donors with a history of pregnancy and 1 to 5% of male blood donors harbor these antibodies. Alternatively, TRALI may be mediated by other bioactive lipids or substances that accumulate during storage and cause a reaction when transfused to susceptible patients. The complex interplay among various donor‐, component‐, and patient‐related factors underlying TRALI guarantees that effective prevention will not be a single or simple intervention but rather will require a multifaceted approach. Perhaps, the most important risk reduction strategy is the effort to ensure appropriate use of blood products and eliminate unnecessary transfusions. Blood collection agencies, however, have more proximate control over donor selection and component management than transfusion practice. AABB has provided some guidance on deferring donors implicated in TRALI and minimizing the preparation of high plasma volume components from donors who have anti‐leukocyte antibodies or are at increased risk of leukocyte alloimmunization. Blood centers have taken various approaches to mitigate the risk of TRALI, and the possible benefit and the inherent limitations of the current strategies will be reviewed. J. Clin. Apheresis 2009. © 2009 Wiley‐Liss, Inc.     

Screening of multiparous women to avoid transfusion‐related acute lung injury: a single centre experience

summary The aim of this study was to investigate which approach for serological testing of multiparous donors might be feasible and effective to reduce the risk of transfusion‐related acute lung injury (TRALI). TRALI is a serious adverse event of blood transfusion. Antibodies to granulocytes and human leucocyte antigens (HLAs) are frequently detected in sera of implicated donors. These donors are often multiparous women. A general deferral of female plasma or screening strategies for leucocyte antibodies has been proposed to increase blood safety. A prospective study was initiated in 2003. Until 2006, serum samples from all female donors reporting three or more pregnancies (n = 229) were screened for the presence of antibodies against granulocytes and HLAs by immunofluorescence and agglutination tests as well as by a commercial HLA enzyme immunoassay. In total, 40% of all multiparous women were reactive in one of the assays. Twenty‐nine percent of the reactive sera contained antibodies to granulocytes but not to HLAs. During the observation period, three TRALI reactions occurred in our hospital, two of which would have been prevented if the screening program had been extended to all previously pregnant donors. We conclude from these data that, not unexpectedly, the number of previous pregnancies is not a reliable indicator for the likelihood of inducing TRALI. More importantly, screening strategies for antibodies that might induce TRALI should probably not be reduced to HLA antibody screening. This finding awaits further research.     

Electronic health record surveillance algorithms facilitate the detection of transfusion‐related pulmonary complications

BACKGROUND: Transfusion‐related acute lung injury (TRALI) and transfusion‐associated circulatory overload (TACO) are leading causes of transfusion‐related mortality. Notably, poor syndrome recognition and underreporting likely result in an underestimate of their true attributable burden. We aimed to develop accurate electronic health record–based screening algorithms for improved detection of TRALI/transfused acute lung injury (ALI) and TACO. STUDY DESIGN AND METHODS: This was a retrospective observational study. The study cohort, identified from a previous National Institutes of Health–sponsored prospective investigation, included 223 transfused patients with TRALI, transfused ALI, TACO, or complication‐free controls. Optimal case detection algorithms were identified using classification and regression tree (CART) analyses. Algorithm performance was evaluated with sensitivities, specificities, likelihood ratios, and overall misclassification rates. RESULTS: For TRALI/transfused ALI detection, CART analysis achieved a sensitivity and specificity of 83.9% (95% confidence interval [CI], 74.4%‐90.4%) and 89.7% (95% CI, 80.3%‐95.2%), respectively. For TACO, the sensitivity and specificity were 86.5% (95% CI, 73.6%‐94.0%) and 92.3% (95% CI, 83.4%‐96.8%), respectively. Reduced PaO₂/FiO₂ ratios and the acquisition of posttransfusion chest radiographs were the primary determinants of case versus control status for both syndromes. Of true‐positive cases identified using the screening algorithms (TRALI/transfused ALI, n = 78; TACO, n = 45), only 11 (14.1%) and five (11.1%) were reported to the blood bank by physicians, respectively. CONCLUSIONS: Electronic screening algorithms have shown good sensitivity and specificity for identifying patients with TRALI/transfused ALI and TACO at our institution. This supports the notion that active electronic surveillance may improve case identification, thereby providing a more accurate understanding of TRALI/transfused ALI and TACO epidemiology.