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.     

Complications pulmonaires de la transfusion (TACO–TRALI)

Pulmonary oedemas occurring during or after a blood transfusion appear as the most frequent serious immediate incidents in the French hemovigilance database. They include transfusion-associated circulatory overload (TACO) and transfusion-related acute lung injury (TRALI). TACO are a major cause of transfusion-related death in France. TRALI are more and more recognized and notified. In no case, pooled fresh frozen plasma (100 donations) treated with solvent–detergent were involved in French TRALI cases. A logigrame will allow hemovigilance officers to better classify pulmonary oedemas in e-fit, the French hemovigilance database.     

Transfusion-related respiratory complications in intensive care: A diagnosis challenge

Transfusion-related respiratory complications can be challenging to diagnose especially in mechanically-ventilated patients in the intensive care unit (ICU) due to the concurrent respiratory symptoms associated with the patients’ primary diagnoses. In this narrative review, transfusion-related respiratory complications, including transfusion-associated dyspnea (TAD), transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), and transfusion-related allergic reaction (TRAR), are briefly presented in light of the recent consensus or experts’ definitions; and the diagnosis issues for ICU patients are discussed. Acute respiratory failure occurring during, or within 6 to 24 hours, of transfusion might be a transfusion-related respiratory complication. The recent updated definitions for TRALI and TACO should assist clinicians to differentiate between possible diagnoses. The issues for ICU clinicians are first to recognize the acute respiratory deterioration and the possible causality between the deterioration and blood transfusion and secondly to make the proper diagnosis. This remains challenging for mechanically-ventilated patients. Clinical assessment to identify ICU patients at particular risk of transfusion-related respiratory complications and non-invasive investigation tools could be beneficial and may help to remind clinicians to be alert to the link between transfusion and worsening of respiratory symptoms in these vulnerable critically ill patients.     

Transfusion-associated circulatory overload

Transfusion-associated circulatory overload (TACO) is cardiogenic pulmonary oedema due to infusion of rapid or large volume blood product. TACO is a frequent, serious, but under-recognized complication of haemotherapy. Presenting symptoms include dyspnoea, cyanosis, tachycardia and increased blood pressure. Pedal oedema, headache, chest tightness and dry cough are additional manifestations. Chest radiographs reveal pulmonary oedema and cardiomegaly. Vulnerable patients are the very young and persons over 60 years. While rapid infusion or massive transfusion are frequently the precipitating factors, relatively small volumes (1–2 units) are sufficient to trigger the congestive heart failure. Both haeme and non-haeme fluids account for the positive fluid balance. Fresh-frozen plasma (FFP) and autologous red blood cells have been implicated as well. Consequences include longer length of intensive care unit and hospital stay. The fatality rate has been reported to be 1–3%, but this may understate the true rate. The incidence has been reported to be 1–8% in orthopaedic surgical populations. In general hospital populations a range of 1 : 708–1 : 4075 red blood cell transfusions is associated with TACO. In the intensive care setting, an incidence of 1 : 356 components has been demonstrated. TACO is frequently confused with transfusion-related acute lung injury (TRALI). In some cases, TRALI and TACO may co-exist. A potentially important diagnostic tool is brain natriuretic peptide. Brain natriuretic peptide is elevated in TACO and a post-transfusion-to-pre-transfusion ratio of 1·5 is indicative of the diagnosis. The test has a sensitivity of 81% and a specificity of 89%. Treatment includes supplementary oxygen, diuretics, placing the patient in a sitting position and therapeutic phlebotomy in 250-ml increments. While rapid infusion is believed to be a contributing factor, optimal infusion rates for the non-emergency situation have not been determined. TACO has been observed with flow rates between 0·9 and 48·1 ml/min. Preventive measures include use of evidence-based transfusion and controlled-rate infusion. Measures that insure the use of standardized blood components, such as derived through apheresis, are likely to favourably impact the incidence of this complication.     

Aktualny stan wiedzy na temat patofizjologii,diagnostyki i zapobiegania TRALI

Transfusion-related acute lung injury (TRALI) is the leading cause of mortality following transfusion of blood components. Characteristic for TRALI is acute hypoxemia during or up to 6 h after transfusion provided that cardiogenic respiratory failure and transfusion-associated circulatory overload (TACO) are excluded.In this article we present: 1) Etiology and pathomechanism of TRALI syndrome including the numerous issues that are still unresolved. Currently accepted is the multiple-event model which involves both the patient and the transfused blood components. The TRALI syndrome may be either immunological or nonimmunological dependant on the various factors that activate neutrophils – the main cells in TRALI pathogenesis. 2) TRALI diagnosis should be based mainly on the clinical presentation due to the variety of pathomechanism of the syndrome; however testing of anti-leukocyte antibodies in transfused blood components, according to ISBT guidelines, is recommended in order to prevent TRALI incidence. 3) Different strategies of TRALI prevention, although up to date no ultimate provisions have been accepted. Transfusion of plasma collected only from men seems to be a promising solution as in many countries that adapted this preventive measure the number of TRALI cases has substantially decreased. 4) Different methods of proceeding with donors who donated blood components that were the cause of TRALI in transfused patients. It still remains an open question whether to defer donors with anti-leukocyte antibodies or multi pregnant women.     

Transfusion‐related acute lung injury and transfusion‐associated circulatory overload

Pulmonary complications of transfusion were once believed to be infrequent and relatively unimportant in terms of morbidity. Transfusion‐related acute lung injury (TRALI) and transfusion‐associated circulatory overload (TACO) are now appreciated as being relatively common and clinically important. TRALI is one of the two most frequent causes of transfusion‐associated death and patients with TACO have longer hospitalizations and increased morbidity. Both entities are diagnosed primarily on clinical grounds but laboratory tests are available which can confirm or supplement the clinical impression. The high‐risk patient for TRALI has not been identified but in TACO, very young or older patients who are transfused too rapidly or with too much volume are the most vulnerable. The mechanism of TRALI is incompletely understood but antibodies in stored blood components certainly play an important role. In TACO, the problem is primarily a mechanical issue. Prompt recognition is the key to successful treatment for both entities.     

How clinicians can minimize transfusion-related adverse events?

Objectives

Transfusion-related adverse events (TRAE) can contribute to patient morbidity and mortality. In this brief narrative review, the strategies that clinicians can apply at the bedside to avoid TRAE are discussed.

Diagnosis of transfusion-related acute lung injury: TRALI or not TRALI?

TRALI is a challenging diagnosis for both the transfusion specialist and the clinician. A Canadian consensus panel has recently proposed guidelines to better define TRALI and its implications. The guidelines recommend classifying each suspected case in one of the following 3 categories: (1) "TRALI," (2) "Possible TRALI," or (3) "Not TRALI." We report the clinical presentation, laboratory evaluation, and management of 3 patients with respiratory failure (RF) following allogeneic blood transfusions. These patients all experienced RF within 6 hr post-transfusion. Based on a review of the clinical and laboratory data and applying the Canadian guidelines, the first patient, a 67-yr-old man with chronic myelomonocytic leukemia, was diagnosed as "TRALI" due to the sudden onset of RF requiring intensive resuscitation. The second patient, a 55-yr-old man with aplastic anemia, was diagnosed as "Possible TRALI" due to pre-existing RF that worsened after blood transfusion. The third patient, a 1-yr-old male, was diagnosed as transfusion associated circulatory overload (TACO) and "Possible TRALI," although his RF improved after treatment with diuretics. In all 3 cases, the blood donor center was informed of the suspected TRALI reactions. The remaining blood products from the donors associated with these reactions were quarantined. After review of the clinical data, the donors associated with cases #1 and #3 were screened by the blood center for granulocyte and HLA antibodies. Using a Luminex flow bead array, the following class I and class II antibodies specific for patient #1 were identified in the respective donor: anti-A25, B8, B18, and anti-DR15, DR 17. Subsequently, donor #1 was permanently deferred. A non-specific IgM anti-granulocyte antibody was identified in the donor associated with case #3, and this donor was subsequently disqualified from plasma and platelet donations. In conclusion, the Canadian guidelines to categorize patients suspected of TRALI provide a useful framework for evaluation of these patients and their respective blood donors.     

The recipient side of TRALI – the role of patient neutrophils

Transfusion‐related acute lung injury (TRALI) is a serious and potentially fatal complication of blood transfusions. The fact that TRALI has been the top cause of transfusion‐related mortalities in the USA over the last 3 years (2004–06) [ 1 ] provides irrefutable evidence of the clinical significance of this syndrome. From this perspective, its importance in transfusion complications surpasses that of blood‐borne viruses and bacterial infections. Despite this, we still do not clearly understand the pathophysiology and pathogenesis of TRALI. This paper presents a TRALI patient or recipient perspective by discussing how thorough serological investigations can be utilized to provide evidence that patient neutrophils are the target cell and to identify the implicated donation/s when there are multiple associated donations.     

Transfusion‐associated circulatory overload (TACO): Time to shed light on the pathophysiology

Transfusion‐associated circulatory overload (TACO) is the most frequent pulmonary complication of transfusion and one of the leading causes of transfusion‐related fatalities. TACO is characterized by new or worsening hydrostatic pulmonary oedema which occurs within 6 h of blood transfusion and results in respiratory distress. Major risk factors for TACO include cardiac failure, renal dysfunction and the degree of positive fluid balance. Suboptimal fluid management and inappropriate infusion practices have also been reported as risk factors for TACO. Unfortunately, the TACO pathophysiology is poorly understood. It can be hypothesized that the pathophysiology of TACO may be generally reflected by a 2‐hit model. The first hit in TACO may be represented by the poor adaptability for volume overload in the transfusion recipient, which is supported by the identification of cardiovascular and renal risk factors for the onset of TACO. The second hit may subsequently be conveyed by the transfused blood product. Remarkably, volume overload alone does not appear to be the only factor triggering the onset of TACO. It can be hypothesized that other factors in the transfused product may play a significant role. In addition, inflammation in the transfused recipient may also be an important feature in TACO. To obtain more insight into the TACO pathophysiology, it will be important to assess and validate potential biomarkers in TACO. In addition, development of currently unavailable TACO‐animal models will provide a useful tool for dissecting the pathophysiologic mechanisms. Collectively, this will aid in improving diagnostic approaches and shed light on possible therapeutic interventions.     

Transfusion-related acute lung injury resulting from designated blood transfusion between mother and child: a report of two cases

Transfusion-related acute lung injury (TRALI) is an underdiagnosed serious complication of blood transfusion characterized by the rapid onset of respiratory distress, hypoxia, and noncardiogenic pulmonary edema during or soon after blood transfusion. The presence of anti-HLA and/or antigranulocyte antibodies in the plasma of donors is implicated in the pathogenesis of TRALI. We report 2 cases of TRALI that were caused by designated blood transfusion between mothers and their daughters; one in a 4-month-old girl who received designated packed RBCs donated by her mother and the second in a 78-year-old mother who received blood from her daughter. In both cases, examination of mother's serum revealed panel-reactive cytotoxic HLA antibodies. It is most likely that the mothers were sensitized from earlier pregnancy and produced HLA antibodies against the daughters' paternally derived HLA antigens. Designated blood transfusion between multiparous mothers and children might add an additional transfusion-related risk owing to the higher likelihood of the HLA antibody-antigen specificity between mother and child.     

New insights in mechanisms of transfusion-related acute lung injury

Transfusion-related acute lung injury (TRALI) is a syndrome characterized by acute respiratory distress following the transfusion of blood components. The pathophysiological hallmark of TRALI is an increased pulmonary microvascular permeability. Several reports demonstrate that the majority of TRALI cases are precipitated by the transfusion of donor antibodies directed against HLA (human leukocyte antigens) or HNA (human neutrophil antigens) expressed on the neutrophils’ surface of the recipient. This antibody- antigen interaction is thought to directly cause neutrophil activation and release of cytotoxic agents, with subsequent endothelial damage and capillary leak. Recent observations, however, indicate that other cells may also play a significant role in TRALI. This review will introduce several possible mechanisms of TRALI including the involvement of other blood cells and of the pulmonary endothelium.     

Transfusion-related acute lung injury: Current understanding and preventive strategies

Transfusion-related acute lung injury (TRALI) is the most serious complication of transfusion medicine. TRALI is defined as the onset of acute hypoxia within 6 hours of a blood transfusion in the absence of hydrostatic pulmonary oedema. The past decades have resulted in a better understanding of the pathogenesis of this potentially life-threating syndrome. The present notion is that the onset of TRALI follows a threshold model in which both patient and transfusion factors are essential. The transfusion factors can be divided into immune and non-immune mediated TRALI. Immune-mediated TRALI is caused by the passive transfer of human neutrophil antibodies (HNA) or human leukocyte antibodies (HLA) present in the blood product reacting with a matching antigen in the recipient. Non-immune mediated TRALI is caused by the transfusion of stored cell-containing blood products. Although the mechanisms behind immune-mediated TRALI are reasonably well understood, this is not the case for non-immune mediated TRALI. The increased understanding of pathways involved in the onset of immune-mediated TRALI has led to the design of preventive strategies. Preventive strategies are aimed at reducing the risk to exposure of HLA and HNA to the recipient of the transfusion. These strategies include exclusion of “at risk” donors and pooling of high plasma volume products and have shown to reduce the TRALI incidence effectively. This review discusses the current understanding of TRALI and preventive strategies available.     

Effet de la déleucocytation des concentrés érythrocytaires sur les réactions transfusionnelles

SubjectIn order to assess the impact of leukocyte reduction, all transfusion reactions reported at Liege Teaching Hospital's Blood Bank 2 years before and after the implementation of universal leukocyte reduction of red blood cells concentrates which started-up on 1 January 2005 were evaluated.Study design and methodsA retrospective analysis of transfusion reactions from 1 January 2003 to 31st December 2006 was undertaken. Data were collected from computerized reports, which were entered as soon as a transfusion reaction was reported. Symptoms were classified in different reaction's categories. Blood cultures, antibody screening and direct antiglobulin test were performed. Differences between the two time periods, before (2003–2004) and after (2005–2006) universal leukoreduction were determined by the Chi-square test and significance was defined as a p value less than 0.05.ResultsDuring period before the implementation of systematic leukoreduction, 68.7% of red blood cells transfused were leukoreduced. A total of 365 transfusion reactions in 91,996 red blood cells units transfused (0.4%) were reported, of which 266 were classified as febrile non-hemolytic transfusion reactions (72.9%), followed by allergic reactions (7.1%) and miscellaneous reactions (3.8%). When comparing the two-time periods, the rate of all transfusion reactions in general significantly decreased from 0.49 to 0.31% (p < 0.001). Therefore, universal leukocyte reduction significantly reduced the rates of febrile non-hemolytic transfusion reactions (0.35% versus 0.24%; p = 0.002) and allergic reactions (0.05% versus 0.01%; p < 0.001).ConclusionUniversal leukocyte reduction significantly reduced the rate of transfusion reactions.     

Transfusion-related acute lung injury: past, present, and future

Noncardiogenic pulmonary edema caused by transfusion has been observed for almost 60 years. Today, we know this entity as transfusion-related acute lung injury (TRALI). TRALI is an uncommon but potentially fatal adverse reaction to transfusion of plasma-containing blood components. It is typified by dyspnea, cough, hypoxemia, and pulmonary edema within 6 hours of transfusion. Most commonly, it is caused by donor HLA antibodies that react with recipient antigens. It may also be caused by biologically active compounds accumulated during storage of blood products, which are capable of priming neutrophils. Without a "gold standard," the diagnosis of TRALI relies on a high index of suspicion and on excluding other types of transfusion reactions. Although current definitions of TRALI depend on symptoms, laboratory parameters can aid in the diagnosis and frequently identify the causative donor unit. As our understanding of TRALI deepens, risk reduction or prevention may become possible.     

Transfusion-associated circulatory overload: A survey among Dutch intensive care fellows

Objectives

Transfusion-associated circulatory overload (TACO) is a severe pulmonary transfusion reaction and leading cause of transfusion-related morbidity and mortality in Europe. TACO is of particular importance in critically ill patients, since they often receive blood transfusions and have multiple risk factors for TACO. This study investigates transfusion practices in patients at risk of developing TACO, and furthermore knowledge concerning risk factors, diagnoses and treatment strategies among Dutch intensive care unit (ICU) fellows.

The Role of Cytokines and Adhesive Molecules in Febrile Non-Hemolytic Transfusion Reactions

Febrile non-hemolytic transfusion reactions occur not infrequently following transfusion. Our understanding of the molecular biology of these reactions has increased dramatically over the past few years. A variety of biological response modifiers have been shown to play a role in these reactions. These chemical messengers include cytokines, complement fragments, antibodies and adhesion molecules. Many of the clinical symptoms associated with these reactions are attributable to activation and generation of these substances. This review article will cover the role of cytokines in generation of non-hemolytic febrile transfusion reactions and the role of activation of adhesion molecules in the generation of TRALI (non-cardiogenlc pulmonary edema). Our ability to modulate the generation of these chemical messengers could help us control clinical symptoms associated with these transfusion reactions.     

Effets indésirables transfusionnels de nature allergique en pédiatrie, étude sur 3 ans

Purpose of the studyIn the transfused patients, in France, in 2011, allergy ranked as the third adverse transfusion reaction. In order to evaluate the incidence and symptomatology of allergic adverse transfusion reactions in the paediatric people, a study was performed.Patients and methodsIt was focused on patients under 18 years of age cared for in hospitals of the Rhone-Alpes area. The national haemovigilance database (e-FIT) reports of allergic transfusion reactions were reviewed.ResultsFrom January 1st 2009 to December 31st 2011, among 2,165 reports, 141 (6.5%) adverse transfusion reaction reports were collected in paediatric patients. Sixty-eight (48.2%) indicated allergic reactions and corresponded to 64 recipients. As regards clinical manifestations, forty-eight (70.6%) indicated cutaneous signs only, 3 (4.4%) mentioned pulmonary signs only and 9 (13.2%) reported both. Urticaria was observed in 38 cases (55.9%). Bronchospasm was notified in 4 cases but there was no angioedema. As for the severity of reactions, one adverse transfusion reaction was severe (grade 2) and 2 were life-threatening (grade 3). The most involved blood component was the apheresis platelet concentrate (40 cases, 58.8%) followed by the red blood cell concentrate (17 cases, 25.0%) and the methylene blue-treated fresh-frozen plasma (11 cases, 16.2%).ConclusionThis study shows that among paediatric recipients, cutaneous signs are predominant in allergic adverse transfusion reactions and that the apheresis platelet concentrate is the most frequently involved blood component.     

TRALI-new challenges for histocompatibility and immunogenetics in transfusion medicine

Antibodies against human leukocyte antigens (HLAs) have long been associated with transfusion-related acute lung injury (TRALI). In contrast to febrile transfusion reactions and refractoriness to platelet transfusions in immunized patients, the causative antibodies in TRALI are present in the transfused blood component, i.e. they are formed by the blood donor and not by the recipient. Consequently, blood components with high plasma volume are particularly associated with TRALI. In addition to antibodies against HLAs, antibodies directed against human neutrophil antigens (HNAs) present in the plasma of predominantly multiparous female blood donors can induce severe TRALI reactions. Especially, antibodies to HLA class II and HNA-3a antigens can induce severe or even fatal ALI in critically ill patients. Over the last decade, the clinical importance of TRALI as major cause for severe transfusion-related morbidities has led to the establishment of new guidelines aimed at preventing this condition, including routine testing for HLA and -HNA antibodies for plasma donors with a history of allogeneic sensitization. This, in turn, poses new challenges for close collaboration between blood transfusion centers and histocompatibility and immunogenetics laboratories, for sensitive and specific detection of the relevant antibodies.     

An audit of reported acute transfusion reactions in Universiti Kebangsaan Malaysia Medical Centre

Transfusion is an irreversible event which carries potential benefits as well as risk to the recipient. The objective of this study was to analyse all reported transfusion reactions of the year 2008 in the Blood Bank Unit of Universiti Kebangsaan Malaysia Medical Centre (UKMMC). This is a retrospective study that was carried out by retrieving data from the laboratory information system. A total of 27842 transfusions were documented and the total reported transfusion reactions were 149. The incidence of transfusion reaction was 1 in 187 of all transfusions (0.54%); in which 69 (0.25%) were allergic in nature and 61 (0.22%) were febrile non-haemolytic transfusion reactions (FNHTR). Hypotensive reactions were identified in 6 (0.02%) patients. There were 9 (0.03%) cases reported with haemoglobinuria where no serological evidence of haemolytic transfusion reaction (HTR) was found. One HTR (0.003%) was identified and this was due to an error in patient identification in the ward. Other specified reactions like transfusion-related acute lung injury (TRALI), bacterial infections, Graft verses host disease (GVHD) were not reported. The highest frequency of the reactions occurred in the red cell transfusions which accounted for 111 cases. In conclusion, the incidences of transfusion reactions are low when compared to those reported by other centres.