Cases Of TRALI Research Articles

Transfusion-Related Acute Lung Injury

We present here a 50-year-old male with a past medical history of aplastic anemia secondary to myelodysplastic syndrome who presented to the hospital with the chief complaint of severe generalized weakness due to acute anemia. He was transfused one unit of blood and developed ARDS 4 hours later. He was diagnosed with transfusion-related acute lung injury and discharged home after symptomatic management. This case report is a typical case of TRALI and deserves to be published in order to inform the general public of clinicians about TRALI, with the goal to improve the notification rate to hemovigilance which remains very low.

A Case Report of Mild TRALI and Literature Review

Abstract Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-associated fatalities. The diagnosis of TRALI is challenging due to lack of pathognomonic laboratory tests and the diagnosis is mainly based on clinical and radiographic findings. The criteria for the diagnosis of TRALI include (1) onset: within 6 hours of transfusion; (2) oxygenation: PAO2/FiO2 ≤300 mm Hg regardless of positive end-expiratory pressure level or oxygen saturation of ≤90% on room air; (3) chest x-ray: bilateral infiltrates on frontal chest radiography; and (4) blood pressure: pulmonary artery occlusion pressure ≤18 mm Hg when measured or no evidence of left atrial hypertension. Although the pathogenesis of TRALI is not fully understood, two different hypothetical pathways have been postulated. One of the pathways is an antibody-mediated, one-hit event (immune TRALI, 89% of cases) and mainly related to the antibodies against the human leukocyte antigen (HLA) or human neutrophil antigen (HNA). The other pathway (nonimmune TRALI) is a two-hit event, and the risk depends on certain predisposing factors, such as underlying pulmonary diseases. However, diagnosis of mild TRALI is challenging due to absence of stridor, wheezing, and rales on physical examination and lack of typical chest x-ray features of TRALI. On the other hand, identification of mild TRALI is important in order to initiate appropriate donor investigation and limit the potential for more severe occurrence in other patients. Recently, we diagnosed a rare case of mild TRALI and report it as follows: A 47-year-old African American male was admitted for relapsed acute myeloid leukemia (AML) who developed therapy-related thrombocytopenia requiring platelet transfusion. Within 15 minutes of starting the transfusion, the patient developed acute dyspnea, hypertension, tachycardia, and hypoxemia with PaO2/FiO2 of 78.9 mm Hg and SaO2 of 92.4%. However, the chest x-ray showed no infiltrates. He was treated with IV steroids, antihistamines, and 15 L of oxygen by face mask with improvement of signs and symptoms within 90 minutes of the reaction. The diagnosis of mild TRALI was confirmed by the detection of anti-HLA class I antibodies in the donor’s plasma. We reviewed the literature, and only four cases of mild TRALI were reported. Mild TRALI can be caused by transfusion of fresh-frozen plasma (2/4), RBCs (1/4), and platelets (1/4). The initial symptoms usually include fever (3/4), chills (4/4), dyspnea (4/4), tachycardia (3/4), and blood pressure changes (2/4 increased in both systolic and diastolic BP, 1/4 increased in systolic BP, 1/4 increased in systolic but decreased in diastolic BP, and 1/4 decreased in diastolic BP). On physical examination, no stridor, wheeze, rales, or urticaria were found (4/4). Laboratory test showed a decrease in the WBC (4/4). Chest x-ray did not show obvious bilateral infiltration and therefore was not required. The symptoms improved rapidly in a few minutes (2/4) to several hours (1/4 in 2 hours and 1/4 in 4 hours). HLA testing showed HLA class I (4/4) or class II (2/4) antibodies in the donor’s plasma. In conclusion, identification of mild TRALI is critical but challenging because diagnosis is based principally on the clinical symptoms and there is no specific laboratory test for mild TRALI. We need to have a high index of suspicion for TRALI in any patient who experiences respiratory symptoms related to transfusion in our daily practice.

The transfusion‐related acute lung injury controversy: lessons from heparin‐induced thrombocytopenia

The transfusion‐related acute lung injury controversy: lessons from heparin‐induced thrombocytopenia

Transfusion-related acute lung injury in an era of TRALI risk mitigation

Abstract Transfusion-related acute lung injury (TRALI) is a rare complication of transfusion, for which the true incidence remains obscure, since there are a number of factors that may lead to misdiagnosis. Despite this, it continues to be the leading cause of transfusion-associated mortality. Here we present a historical case of TRALI in an elderly female who received group AB plasma and discuss how current mitigation strategies would likely have prevented its occurrence. It is important to remember that both immune and non-immune factors play a role in TRALI pathogenesis, and although current preventative strategies may decrease TRALI’s incidence, they likely will not eliminate it. Immunohematology 2015;31:155–158.

A Role for SEM in Autopsy Cases of TRALI

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.

Les TRALI au CHU de Nancy : une incidence reconsidérée après l’application stricte des critères de Toronto

“Transfusion-related acute lung injury” (TRALI) is a post-transfusion lesional pulmonary edema, potentially severe, better defined since the conference of Toronto in 2004. The incidence of TRALI reported in France remains low in part because of its ignorance by physicians. The objective of our study was to evaluate retrospectively transfusion accidents with respiratory complications that occurred in Nancy University Hospital and reported to the haemovigilance between 1996 and 2006, from the software “Traceline” listing all the blood transfusion complications from signs observed. The analysis of the files has been performed by applying rigorously diagnostic criteria of Toronto. Forty-one cases of respiratory complications were found in 34,573 blood products. Ten cases of TRALI were diagnosed while only one case had been reported to the haemovigilance. The remaining nine cases were previously labeled transfusion-associated circulatory overload (TACO). No cases of TRALI have been identified in the ICU. Our work can find an incidence of TRALI 10 times greater than previously reported. Ignorance of TRALI and the lack of consensus definition before 2004 are not sufficient to explain these results. This study demonstrates the potential interest of database and computerized declaration system based on the symptoms observed. It highlights the vulnerability of the current haemovigilance too dependent on a single medical observer. Although TRALI are recognized as serious complications, sometimes requiring resuscitative care, our work was not isolated severe TRALI in ICU. Physician awareness of TRALI to the identification and to the declaration, including ICU should be continued. Finally, the diagnostic criteria for TRALI must be adapted to the ICU.

Adverse transfusion reactions with respiratory symptoms

Background: Quite numerous cases of adverse reactions present with respiratory symptoms, TRALI, TACO and anaphylaxis being the most frequent severe reactions. In our study we describe TACO cases in Slovenia from 2003–2010. Methods: All reported adverse transfusion reactions with respiratory symptoms were analysed. Results: Of the 1,333 ATR reported, 104 cases (7.8 %) were assessed as serious. There were 38 (36.5 %) cases of allergy and anaphylaxis, 4 cases of TRALI (3.8 %), 33 cases of TACO (31.7 %). The number of reported TACO gradually increased from 2 cases in 2004 to 15 in 2009. It was found that 48 % of the reported TACO cases were lifethreatening. In 91 % of them, red cells were transfused. In 76 % of cases the patients were over 60 years of age. Conclusions: A significant proportion of ATR were those with dyspnea. Although in the period from 2003 to 2009, the number of reported ATR in Slovenia was on the increase, it is assumed that ATR with respiratory complications is still under-reported. In the last few years, a great percentage of red cell components was leukocyte depleted and male only fresh frozen plasma was made available for clinical use, which is an important reason for the low number of reported TRALI cases. TACO is quite a frequent serious ATR in Slovenia. Preventive measures need to be taken, such as the blood-product dose or infusion rate reduction in high-risk patients and improvement of patient monitoring during blood administration.

Extracellular DNA Traps Are Associated with Pathogenesis of TRALI in Humans and Mice

Abstract 37Transfusion-related acute lung injury (TRALI) is a serious complication of blood transfusion occurring within 6 hours of transfusion. It is characterized by hypoxemia, respiratory distress and pulmonary infiltrates (Kleinman et al. Transfusion 2004) and is the leading cause of transfusion-induced death. The biological processes contributing to TRALI are still poorly understood. All blood products can cause TRALI, and to date no specific treatment is available. A “two-event model” has been proposed as the trigger (Silliman et al Blood 2007). The first event may include surgery, trauma or infection; the second involves the transfusion of anti-neutrophil antibodies or bioactive lipids within the blood product. Together these events induce neutrophil activation and sequestration in the pulmonary capillaries (Looney et al J Clin Invest 2006) resulting in endothelial damage and capillary leakage (Shaz et al Blood 2011). In response to pathogens or under stress, activated neutrophils have the ability to release neutrophil extracellular traps (NETs) (Brinkmann Science 2004; Fuchs et al J Cell Biol 2007) that are composed of DNA fibers decorated with histones and antimicrobial proteins (Urban PLoS Pathog 2009) originally contained in the neutrophil granules. Although protective against infection, these NETs are injurious to tissue (Xu et al Nat Med 2009, Xu et al J Immunol 2011), activate platelets (Fuchs et al PNAS 2010) and can contribute to the pathology of inflammatory diseases (Kessenbrock et al Nat Med 2009, Garcia-Romo Sci Transl Med 2011). The purpose of this study was to determine whether NETs are formed in patients during TRALI and whether they contribute to TRALI in a mouse model.Here we show that NETs biomarkers are present in TRALI patients' blood and that the antibody responsible for the most severe TRALI cases and that is directed against human neutrophil antigen (HNA)-3a (Davoren et al Transfusion 2003; Greinacher et al Nat Med 2010) stimulates NETs generation from primed human neutrophils when compared to a control antibody. This effect was inhibited when FcgRIIa-binding sites were blocked prior to antibody incubation. Moreover, anti-HNA-3a F(ab')2 fragments had no effect on NETs generation. These results allowed us to conclude that FcgRIIa activation was required in anti-HNA-3a antibody-mediated NETosis.We next used an in vivo model of antibody-induced TRALI in mice (Looney et al J Clin Invest 2006; Looney et al. J Clin Invest 2009; Hidalgo et al Nat Med 2009). In this two-event model, BALB/c mice are injected i.p. with a low-dose of LPS and 24 hours later are infused with an anti-MHC class I monoclonal antibody (anti-H-2Kd). Two hours later, we measured arterial blood oxygen saturation to document lung function and the lung injury markers were quantified. As observed in blood from TRALI patients, we detected a significant increase in the concentration of circulating NETs biomarkers in mice with TRALI compared to mice that were challenged only with LPS. Multiphoton analysis of fixed lung tissue showed strong staining for citrullinated histone H3 (a phenomenon already described to correlate with NETs formation (Wang et al J Cell Biol 2009; Li et al J Exp Med 2010)) collocalizing with DNA streaks in the alveoli of mice with TRALI. Moreover, we found NETs in abundance in the TRALI-affected alveoli of mice by transmission electron microscopy. We demonstrate that intranasal DNaseI pretreatment of the mice prior to antibody infusion prevented NETs accumulation in the alveoli and also improved the lung function of the mice experiencing TRALI by increasing their arterial blood oxygenation. These results support the hypothesis that NETs are indeed formed in the inflamed lungs during TRALI and contribute to the disease process and thus, could be targeted to prevent or treat TRALI. Disclosures:No relevant conflicts of interest to declare.

Mechanism of transfusion-related acute lung injury induced by HLA class II antibodies

AbstractTransfusion-related acute lung injury (TRALI) is the leading cause of transfusion-associated mortality in the United States and other countries. In most TRALI cases, human leukocyte antigen (HLA) class II antibodies are detected in implicated donors. However, the corresponding antigens are not present on the cellular key players in TRALI: neutrophils and endothelium. In this study, we identify monocytes as a primary target in HLA class II–induced TRALI. Monocytes become activated when incubated with matched HLA class II antibodies and are capable of activating neutrophils, which, in turn, can induce disturbance of an endothelial barrier. In an ex vivo rodent model, HLA class II antibody–dependent monocyte activation leads to severe pulmonary edema in a relevant period of time, whenever neutrophils are present and the endothelium is preactivated. Our data suggest that in most TRALI cases, monocytes are cellular key players, because HLA class II antibodies induce TRALI by a reaction cascade initiated by monocyte activation. Furthermore, our data support the previous assumption that TRALI pathogenesis follows a threshold model. Having identified the biologic mechanism of HLA class II antibody–induced TRALI, strategies to avoid plasma from immunized donors, such as women with a history of pregnancy, appear to be justified preventive measures.

Transfusion-related acute lung injury

Sir, Transfusion-related acute lung injury (TRALI) is an uncommon, probably underrecognized complication of transfusion of plasma-containing blood components, which is characterized by acute respiratory distress. It is a clinical diagnosis and may be diagnosed when acute lung injury (ALI) occurs during or within six hours of transfusion in a patient without pre-existing ALI, in the absence of temporally related alternative risk factors for ALI (e.g., sepsis, shock, cardiac failure, etc.).[1] This communication discusses a case of TRALI in a middle-aged woman. A 52-year-old female patient with a diagnosis of inoperable carcinoma of the uterine cervix, received whole blood transfusion, in view of severe anemia. Before blood transfusion, she was alert, oriented, with no cardiorespiratory abnormality on clinicoradiological evaluation. Her vital parameters were normal and total leukocyte count was 8700/mm3 with normal blood biochemistry. After receiving approximately 200 ml of blood for over two hours, she complained of breathlessness, which progressively increased over the next 20 minutes. On examination she was febrile, tachypneic (respiratory rate 32/minute), slightly cyanotic, with a pulse rate of 120/minute, blood pressure 90/60 mmHg, and SpO2 68%. The jugular venous pressure (JVP) was normal and chest auscultation revealed bilateral basal fine inspiratory crackles with normal breath sounds. Sinus tachycardia was noted on an electrocardiogram (ECG). An urgent X-ray chest showed bilateral patchy infiltrates in the mid- and lower zones with normal heart size, suggestive of noncardiogenic pulmonary edema. Echocardiography also ruled out cardiogenic dysfunction. Hematological investigations at this stage showed a total leukocyte count of 3200/mm3, with no evidence of any hemolytic process. In the absence of other mechanisms to explain ALI, a diagnosis of TRALI was made. The blood transfusion was stopped immediately and she was managed with oxygen therapy and intravenous fluids that resulted in a gradual improvement of dyspnea and oxygen saturation. She became completely chest asymptomatic after three days, with a normal chest X-ray. The reported incidence of TRALI in medical literature is one in 5000 transfusions and this may actually be much higher as TRALI is usually an underrecognized and underreported entity.[2] TRALI has been associated with antibodies to WBCs in transfused blood components. Less frequently, it has been associated with leukocyte antibodies in the transfusion recipient. It has also been linked to the infusion of biologically-active lipids in stored cellular blood components.[3] A mild form of TRALI can present with dyspnea and fever, while more severe forms can have severe respiratory distress that can quickly progress to respiratory failure. Other features include hypotension, frothy endotracheal secretions, and so on. Transient leucopenia, as noted in our patient, is occasionally observed and is believed to be due to the sequestration of leukocytes in pulmonary circulation. It is important to distinguish TRALI from volume overload, as the treatment of the two conditions is markedly different. Diuretics are contraindicated in TRALI and there is no role for steroids also. Severe forms of TRALI may require mechanical ventilation.[3] Suspected cases of TRALI should be reported to the blood bank, to permit evaluation and deferral of high-risk donors, especially multiparous females. TRALI can be best prevented by avoiding unnecessary blood-product transfusions in selected populations.

Characterization of the Human Neutrophil Alloantigen (HNA) 3a.

Abstract 24Transfusion-related acute lung injury (TRALI) has been recognized as a frequent cause of transfusion-associated major morbidity and mortality in the Western world. About 80% of reported TRALI cases have been associated with the transfusion of blood products containing leukocyte alloantibodies (Middelburg et al., 2008). Up to 28% of severe and fatal TRALI cases have been reported to be associated with antibodies directed against the human neutrophil alloantigen (HNA)-3a, previously known as 5b (Reil et al., 2008). Since the membrane molecule bearing the HNA-3a/b polymorphism is still unknown, we initiated a study with the objective of elucidating the molecular basis of HNA-3a.For characterization of HNA-3a, we first precipitated HNA-3a from biotinylated HNA-3a expressing neutrophils by the use of HNA-3a antibodies, cell solubilisation with Triton-X100 and Protein G beads coupled with goat anti-human IgG. After electrophoretic separation of the immunoprecipitated proteins by SDS-PAGE and transfer onto membrane, we observed in Western blot analysis a broad band of 80-100 kDa which shifted to 64 kDa after deglycosylation with the N-glycosidase PNGase F. Control plasma samples and/or the use of HNA-3a negative granulocytes did not show these bands.Immunoprecipitates of non-biotinylated granulocytes were purified by μC18 tips and concentrated by vacuum drying. Peptide mixtures were separated and analysed using ultra high performance liquid chromatography and tandem mass spectrometry. Proteins were identified by aligning all obtained spectra with a protein database. Ten peptides were identified which were only present in the HNA-3a precipitates but not in the control precipitates. These peptides were found to be parts of the choline transporter-like protein 2 (CTL2 ) with six peptides matching to the first of the ten extracellular domains.We then assessed a panel of 54 individuals serologically typed for HNA-3a for nonsynonymous mutations in the gene SLC44A2 encoding CTL2 by sequence-specific PCR. The single nucleotide polymorphism 461 G>A resulting in an amino acid substitution from arginine to glutamine at position 154 was fully concordant with the HNA-3a/b phenotypes of these 54 individuals. In addition 461G (154Arg) representing the HNA-3a allele was always found in patients who developed TRALI due to HNA-3a alloantibody transfusion, whereas 461A (154Gln) representing the HNA-3b allele was solely present in all blood donors who formed HNA-3a alloantibodies. In a population study of 3700 individuals using DNA microarrays, 176 (4.8%) were homozygous for A461 (HNA-3b), 1188 (32.1%) were heterozygous (AG461), and 2336 (63.1%) were homozygous for G461 (HNA-3a). Finally, we expressed parts of the first extracellular domain of CTL2 in E. coli which included the amino acid position 154. After culturing, fusion proteins were isolated from the bacteria and transferred on membrane. By immunoblotting, specific signals were only obtained with anti-HNA-3a antibodies containing plasma samples but not with controls.We conclude that the HNA-3a/b polymorphism is caused by a single nucleotide polymorphism at position 461G>A in the gene encoding the choline transporter-like protein 2 resulting in an arginine (R) to glutamine (Q) amino acid substitution at position 154. This finding provides the basis for the development of assays allowing large scale screening of blood donor samples for the presence of HNA-3a antibodies. Such screening will contribute to the reduction of severe TRALI. Disclosures:No relevant conflicts of interest to declare.

Frequency and severity of transfusion-related acute lung injury – German haemovigilance data (2006–2007)

In an observational cohort study (2006-2007) the Paul-Ehrlich-Institut collected epidemiological data to investigate the frequency and causes of TRALI. Diagnosis of TRALI was confirmed according to criteria of the European Haemovigilance Network. Subsequent testing of white blood cell antibodies (WBC-Ab) against HLA or human neutrophil alloantigens was performed. Of a total of 187 reported TRALI cases, 44 could be confirmed consisting of 35 cases of antibody-mediated TRALI and nine cases of non-immune-mediated TRALI. Eight of 44 affected patients (18%) had a fatal outcome, seven cases with WBC-Ab positive plasma donors and one case with red blood cell donors. WBC antibodies were found in one male and 39 female donors. In 34 female donors, a history of pregnancy was confirmed. WBC-Ab positive donors presented four HLA class I antibodies, 15 HLA class II antibodies, 13 HLA class I and class II antibodies, one HNA-2a, and seven HNA-3a antibodies. WBC antibodies matching with recipient antigens were found exclusively in 28 female donors; 26 FFP donors, one platelet donor and one red blood cell donor. Reporting frequency of immune-mediated TRALI was 1:66,000 for fresh frozen plasma, 1:2.86 million for red blood cell concentrates and 1:420,000 for platelet concentrates. Reporting frequency of TRALI-related fatalities was 1:285,000 for FFP. Haemovigilance data show the significance of female donors with a history of pregnancy for the development of antibody-mediated TRALI. Manufacturing of FFP from male plasma and female donor screening for WBC-Ab could represent preventive measures.

Developing Specific Therapeutic Strategies for Transfusion-Related Acute Lung Injury. An Overview of Potentially Useful Animal Models

Transfusion-related (TR)- acute lung injury (ALI) is the leading cause of transfusion-related morbidity and mortality. The pathogenesis of TRALI is thought to be a "two hit"-entity: the "first hit" is (any) proinflammatory pulmonary condition (e.g., pneumonia, sepsis or lung contusion) resulting in activation of lung endothelium with sequestration of polymorphonuclear neutrophils - the "second hit" is provided by transfusion of a blood product. Either antibodies against neutrophils are thought to be implicated in the activation of the sequestrated neutrophils, or bioactive lipids (which accumulate during storage of blood products) induce the "second hit", finally resulting in lung injury. Preventive measures do not prevent all TRALI cases. Also, TRALI is most probably underdiagnosed. In this review, we call for the development of therapeutic approaches for this potentially life-threatening disease. Several interventions which are beneficial in ALI and may also be beneficial in TRALI are discussed. The application of these interventions requires the development of clinically relevant TRALI animal models. We discuss the present TRALI animal models and their shortcomings and propose future animal models, in which clinically relevant "first hits" can be applied, thereby imitating the complex clinical situation.

Œdème pulmonaire lésionnel post-transfusionnel. À propos d'un cas

A transfusion-related acute lung injury (Trali) is a noncardiogenic lung oedema occurring within six hours following the infusion of a blood component. It is a under-recognized transfusional accident, for which the aetiology and physiopathology are still controversial, evoking immunological or nonimmunological mechanisms which do not seem sufficient per se to cause this accident. A predisposing condition, associated with leucostasis in pulmonary vessels, is required. The pulmonary lesion is due to the activation of neutrophils in contact with endothelial cells of lung micro-capillary vessels. We report a case of Trali following the transfusion of the first red blood cells unit to a 26-year-old young woman.

A pediatric case of transfusion‐related acute lung injury following bone marrow infusion

TRALI is a rare but serious complication associated with transfusion, and known to occur following infusion of all types of plasma-containing blood products. However, only one adult case of TRALI after allogenic marrow graft has been reported. In this study, we present a pediatric case possibly associated with allogenic marrow infusion. A 10-yr-old girl was referred to our hospital for the treatment of acute myeloid leukemia. She underwent allogenic bone marrow transplantation from her HLA-2-loci-mismatched mother. During conditioning, she suffered from bacterial sepsis, but it had improved with antibiotics until day 0 of transplantation. Two h after starting the marrow infusion, she developed severe hypoxia. We discontinued the infusion and started steroids, which improved her respiratory condition. However, she developed respiratory failure again after resuming infusion of the graft. Despite intensive care with mechanical ventilation, the patient died of endotoxin shock five days after transplantation. Although we could not identify the antibody which might have been involved in the respiratory distress, the clear temporal relationship between marrow infusion and respiratory distress suggested that similar acute lung injury to TRALI might have occurred following allogenic marrow infusion in the present case.

How do we investigate and manage donors associated with a suspected case of transfusion‐related acute lung injury

SUMMARY Overall, there are several components that we believe arecriticalforthesuccessfulinvestigationofasuspectedcaseof TRALI. One is verbal communication with the hospitaltransfusion service and the clinicians taking care of thepatient, the importance of which can not be overstated.Data that may be missed or understated on a form areoften made clear when questions are asked directly to theclinician. Additionally, communication with the clinicalstaff improves TRALI education and awareness andstreamlinesthereportingoffuturesuspectedTRALIcases.In short, verbal communication with the hospital trans-fusion service and clinical staff facilitates a timely andthorough investigation. It also ensures the capture ofvital information that assists in the clinical diagnosisand donor management of suspected TRALI cases.Equallyimportantisaclinicalclassificationthatisconsis-tent with what other institutions are using to documentcases of TRALI. To better understand TRALI, larger casenumbers need to be analyzed and studied, and onlythrough consistent reporting and classification can thisbe accomplished. We currently rely on the working de-finition recommended by the Canadian consensusconference panel for TRALI and possible TRALI. We havemade some modifications to the Canadian consensusconference panel for our classifications, but these modifi-cations are for the purposes of donor management only.Aslongascompletedocumentationismaintained,theuseof these modifications should not affect our ability toshare data with other institutions that do not use similarmodifications.Despite our best efforts to establish a consistent andeffective way to manage suspectedTRALI cases, the man-agement of donors associated withTRALI remains a diffi-cult task given that TRALI remains an incompletelyunderstood reaction. Contributing to the problem is theinconsistent recognition and reporting ofTRALI that con-tinues to occur from the bedside to the collecting facility,anissuethatultimatelyhampersthebloodcenters’abilityto recognize and prevent potentialTRALI reactions.Thereis great promise that reporting of suspectedTRALI eventswillimprovesignificantlyoncetheAABB’seffortstoestab-lish a US hemovigilance system come to fruition. Weexpect that these efforts will have similar success to pro-gramsalreadyestablishedinternationally.AUShemovigi-lance system will make great strides in improving datacollection and may provide new insight into additionalrisk factors for TRALI in donors.The approach described has been in place for UnitedBlood Services since 2006 and thus far has been effectiveat providing a consistent framework to ourTRALI investi-gations. Over the past several years, we have investigatedapproximately 30 to 40 suspected cases ofTRALI per year.In 2007, we have had 10 TRALI investigations to date, ofwhich 2 were classified as TRALI or likely to be TRALI.Sinceimplementationofournewapproach,donortestinghas been reduced from previous years; this is a result ofmore selective donor testing under the newly designedalgorithm. In the past, only donors with antibody toHNA-3a (5b) were deferred. Now, with the criteria fordonordeferralexpanded,implementationofthisprotocolhas resulted in the deferral of more donors.Our approach represents only one of many potentialways to handle donors associated with TRALI. To whatdegreeadonoristrulyatriskforcausingTRALIisnotwellknown and thus accounts for the variability in possiblestrategies. Nevertheless, our current approach representswhat we believe to be an effective and judicious strategy

A comparison of complication rates based on published haemovigilance data

Haemovigilance is defined as the collection of information on complications of transfusion, the analysis of the data, and suggestions for improvement in the transfusion service. A national haemovigilance system is of value in identifying possible areas in need of improvement in the national transfusion system. Haemovigilance becomes even more important if the system is used to compare the situation in one country with the situation in other countries, e.g. if the countries differ significantly in products used. The current study focuses on immunological transfusion complications, especially TRALI, as published in haemovigilance reports from Denmark, Norway, Sweden and the UK. In Norway immunological transfusion reactions occurred 96.7 times per 100 000 red cell (RBC) transfusion, 231.1 times per 100 000 thrombocyte (Trc) concentrate transfusion and five times per 100.000 transfusions of solvent detergent treated plasma (SD plasma). Denmark and the UK have similar rates of transfusion reactions to RBC and fresh frozen plasma (FFP), but quite different for Trc (0.5 vs. 4.9 per 100 000). In 49% of reported TRALI the causative product is FFP, but no case of TRALI after SD plasma transfusion has been reported. When considering all reports for immunological complications in Norway, the most striking is the very small number of reports related to SD plasma. Comparing data from Denmark and the UK shows a big difference in reactions caused by thrombocyte concentrates that may reflect different production methods in the two countries. TRALI is most often caused by FFP, but has never been reported after SD plasma transfusion. Heamovigilance data can be valuable in choosing the safest products available.

Transfussion – related acute lung unjury (TRALI) – the preventable danger in intensive care?

Institute of Immunology Rikshospitalet-Radiumhospitalet Medical Centre University of Oslo 0027 Oslo, Norway e-mail: bjagees@online.no Tel.: +47 2250 6078 Fax: +47 2307 3510 duction of TRALI by HLA class-II antibodies are discussed, and it is pointed out that monocytes express the antigens, while neurophils and endothelial cells first demonstrate the antigens after activation. Thus, both antibody-activated monocytes and non-immune activating mechanisms could induce HLA class-II expression on neutrophils and endothelial cells. Dr. Wallis has observed TRALI with a frequency of 1 in 7900 units of FFP transfused and a high rate of fatality. He points out that the incidence of TRALI is underestimated because complex and milder cases are easily missed, and refers to a prospective trial which demonstrated that 1 in 50 units of FFP caused some cardiorespiratory impairment. He also points out the strong relationship between ARDS and blood transfusion. Taken together with the above-mentioned prospective trial, he suggests that milder unrecognized forms of TRALI may be much more frequent than previously appreciated. Based on haemovigilance data from Scandinavia and the UK, Dr. Flesland demonstrates that TRALI is observed most frequently after transfusion of FFP, followed by red blood cells and platelets, however not after solvent detergent-treated (SD) FFP (Octaplas). He also observes strikingly lower rates of “allergic” (febrile, urticarial and anaphylactoid) reactions after transfusion of SD FFP than after transfusion of red blood cells and platelets. These reactions are not life-threatening, but most unpleasant for the patient, and labour-consuming. They are caused by antigens, antibodies and cytokines in plasma, which are substances that either are diluted or neutralized by pooling in the production process of SD FFP. The fact that no definite cases of TRALI have been reported after transfusion of many million units of SD FFP can best be explained by: • Pooling, which results in dilution and neutralization of leukocyte antibodies; • removal of cells/cell fragments together with solvent detergent treatment which reduces the amount of Intensive Care Med (2007) 33[Suppl 1]:S1–S2 DOI 10.1007/s00134-007-2872-4

Commentary on TRALI in Leukemia

The paper by Fung YL and Williams BA describes TRALI in leukemic children in order to raise awareness of the need to include this in the differential diagnosis of acute respiratory distress. Detection of TRALI in children with other co-morbidities is difficult. Well-documented cases of TRALI in children are few due to the lack of recognition and difficulty in identifying the antibodies since these may not be always present. Hematology/oncology patients who are chronically transfused and are allo-immunized are at greater risk than the general pediatric population. Thus an awareness of this reaction to blood transfusion helps facilitate prompt treatment and preventive measures.

Transfusion-Related Acute Lung Injury (TRALI): A Retrospective Analysis of 119 Cases.

Following Institutional Review Board approval, detailed data involving patient, product, and clinical factors was retrospectively gathered on 119 TRALI cases identified between 1991 and 1998 at University of Alberta Hospital in Edmonton, AB. This data was gathered as a complement to previously published work (Silliman et al, Blood 2003: 101: 454) on the epidemiology and etiology of TRALI which consisted of 90 sequentially-identified TRALI reactions in 81 patients. In the current study we sought additional detailed clinical and laboratory data on these cases and others identified during the stated time period. Our aim was to help characterize patients who get TRALIs and/or to identify clinical correlates of TRALI. All TRALI were identified on the basis of 1) acute onset of respiratory distress mandating urgent medical intervention as the predominant symptom (peripheral or central cyanosis was noted in virtually all cases and all required supplemental oxygen.); 2)symptoms temporally associated with transfusion of a blood product, and 3) no other cause for the acute respiratory deterioration evident. All diagnoses were reviewed by a transfusion medicine physician. Data was abstracted onto prepared questionnaire forms by 2 of us (LKB and LP) following detailed review of hospital charts and transfusion service records. An electronic database was then prepared using deidentified forms (unique patient code substituted for name and date of birth) and data entered by double entry to assure accuracy. Not all data fields were available on all patients. Preliminary data analysis of these TRALI cases reveals:1.Mean age of TRALI patients: 39.07 years (range 3 mos – 91 years).2.Gender: 49% male, 51 % female3.Hypoxemia: Arterial blood gases available on 41 cases. All hypoxemic on basis of O2 saturation < 90% on room air or higher FIO2.4.Diagnosis of malignancy: 77 / 119 = 65 % of which 54 (45%) were on chemotherapy. Most of the malignancies were hematological.5.Cardiopulmonary bypass: 13 patients: 9 coronary artery bypass grafts (one with valve replacement), 3 valve replacements and one ventricular septal defect closure6.Surgery: 58 cases with preceding surgery within 1–2 days of TRALI (17 central venous cather insertions, 4 endoscopy or bronchoscopy and 37 other major or minor surgery)7.Time from initiation of transfusion to onset of symptoms: < 15 mins (n=15), 15 min – 1 hr (n=56), 1–2 hrs (n=14), unknown (n = 34)8.Type of venous access used for transfusion: central line (n = 24), peripheral line (n=7), unknown (n=63)9.Pre-transfusion white blood cell (WBC) count x 10-9/L: Available in 107 cases.. Average = 13.8 (range 0.1 – 259). WBC > 30: n = 8; WBC < 1.5: n = 40; WBC 1.1–1.5: n = 3; WBC 0.6–1.0: n = 9; WBC 0.3–0.5: n = 21; WBC 0.2: n = 4; WBC 0.1: n=3.Although these data are retrospective and limited, they suggest that TRALI can be seen in any age group, is equally common in males and females, is most often rapid in onset (15 min – 1 hour), and can occur even at low WBCs. Although it is unclear from the present data alone, an increased frequency of TRALI was noted in a nested case-control study (see reference above) in patients with underlying hematological malignancy and antecedent cardiopulmonary bypass.