A possible case of recipient anti-neutrophil and anti-human leukocyte antigen antibody-mediated fatal reverse transfusion-related acute lung injury.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is a transfusion complication often mediated by recipient exposure to plasma from donors with human leukocyte antigen (HLA) and human neutrophil antigen (HNA) antibodies. Recipient anti-donor HLA or HNA antibodies have rarely been implicated. STUDY DESIGN AND METHODS: Herein, we describe a case of fatal TRALI mediated by recipient anti-HLA and anti-HNA antibodies. Cognate antibody-antigen match was confirmed with serologic and molecular assays. RESULTS: A 69-year-old G5P5 female with no prior transfusion history and metastatic cholangiocarcinoma with thromboembolic complications presented with heart failure and dyspnea. She was transfused 15 ml of a unit of Fya -negative red blood cells and subsequently developed acute onset dyspnea, hypoxemia, hypotension, and fever. Clinical investigations revealed bilateral infiltrates on chest X-ray and cognate recipient HLA and HNA antibodies to donor antigens. The patient died of acute respiratory failure within 24 h of transfusion. In total, the patient had Fya , HLA Class I, HNA, and human platelet antigen (HPA) alloantibodies. The 63-year-old female donor had detectable HLA class II antibodies (recipient class II genotype unavailable). CONCLUSION: The pathophysiology of TRALI has traditionally been ascribed to underlying conditions that put the recipient at risk in combination with donor biological response modifiers. This case illustrates alternative pathogenic mediators including alloantibodies to donor HLA and HNA. Additional studies to determine the contribution and frequency of recipient alloantibodies in TRALI may inform future mitigation strategies to further reduce the incidence of TRALI, particularly in female transfusion recipients.

Evaluation of Platelet Responses in Transfusion-Related Acute Lung Injury (TRALI).

Platelets are versatile cells which are capable of eliciting nonhemostatic immune functions, especially under inflammatory conditions. Depending on the specific setting, platelets may be either protective or pathogenic in acute lung injury and acute respiratory distress syndrome (ARDS). Their role in transfusion-related acute lung injury (TRALI) is less well defined; however, it has been hypothesized that recipient platelets and transfused platelets both play a pathogenic role in TRALI. Overall, despite conflicting findings, it appears that recipient platelets may play a pathogenic role in antibody-mediated TRALI; however, their contribution appears to be limited. It is imperative to first validate the involvement of recipient platelets by standardizing the animal models, methods, reagents, and readouts for lung injury and taking the animal housing environment into consideration. For the involvement of transfused platelets in TRALI, it appears that predominantly lipids such as ceramide in stored platelets are able to induce TRALI in animal models. These studies will also need to be validated, and moreover, the platelet-derived lipid-mediated mechanisms leading to TRALI will need to be investigated.

Update on the pathophysiology of transfusion-related acute lung injury.

PURPOSE OF REVIEW: The aim of this study was to discuss recent advances regarding the pathogenesis of transfusion-related acute lung injury (TRALI), which highlight the pathogenic role of macrophages. RECENT FINDINGS: TRALI remains a leading cause of transfusion-related fatalities, despite the success of the mitigation strategy, and therapeutic approaches are unavailable. Neutrophils (PMNs) are recognized pathogenic cells in TRALI. Macrophages have previously also been suggested to be pathogenic in mice via binding of C5a to their C5a-receptor, producing reactive oxygen species (ROS), which damages the pulmonary endothelium. Recent work has further highlighted the role of macrophages in the TRALI-pathogenesis. It has been shown that the protein osteopontin (OPN) released by macrophages is critical for pulmonary PMN recruitment in mice suffering from TRALI and that targeting OPN prevents the occurrence of TRALI. Another recent study demonstrated the importance of M1-polarized alveolar macrophages in murine TRALI induction by showing that α1-antitrypsin (AAT) overexpression prevented TRALI in mice through decreasing the polarization of alveolar macrophages towards the M1 phenotype. SUMMARY: Apart from PMNs, macrophages also appear to be important in the pathogenesis of TRALI. Targeting the pathogenic functions of macrophages may be a promising therapeutic strategy to explore in TRALI.

Risk factors, management and prevention of transfusion-related acute lung injury: a comprehensive update.

Introduction: Despite mitigation strategies that include the exclusion of females from plasma donation or the exclusion of females with a history of pregnancy or known anti-leukocyte antibody, transfusion-related acute lung injury (TRALI) remains a leading cause of transfusion-related morbidity and mortality. Areas covered: The definition of TRALI is discussed and re-aligned with the new Berlin Diagnostic Criteria for the acute respiratory distress syndrome (ARDS). The risk factors associated with TRALI are summarized as are the mitigation strategies to further reduce TRALI. The emerging basic research studies that may translate to clinical therapeutics for the prevention or treatment of TRALI are discussed. Expert opinion: At risk patients, including the genetic factors that may predispose patients to TRALI are summarized and discussed. The re-definition of TRALI employing the Berlin Criteria for ARDS will allow for increased recognition and improved research into pathophysiology and mitigation to reduce this fatal complication of hemotherapy.

A consensus redefinition of transfusion-related acute lung injury.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is a serious complication of blood transfusion and is among the leading causes of transfusion-related morbidity and mortality in most developed countries. In the past decade, the pathophysiology of this potentially life-threatening syndrome has been increasingly elucidated, large cohort studies have identified associated patient conditions and transfusion risk factors, and preventive strategies have been successfully implemented. These new insights provide a rationale for updating the 2004 consensus definition of TRALI. STUDY DESIGN AND METHODS: An international expert panel used the Delphi methodology to develop a redefinition of TRALI by modifying and updating the 2004 definition. Additionally, the panel reviewed issues related to TRALI nomenclature, patient conditions associated with acute respiratory distress syndrome (ARDS) and TRALI, TRALI pathophysiology, and standardization of reporting of TRALI cases. RESULTS: In the redefinition, the term "possible TRALI" has been dropped. The terminology of TRALI Type I (without an ARDS risk factor) and TRALI Type II (with an ARDS risk factor or with mild existing ARDS) is proposed. Cases with an ARDS risk factor that meet ARDS diagnostic criteria and where respiratory deterioration over the 12 hours before transfusion implicates the risk factor as causative should be classified as ARDS. TRALI remains a clinical diagnosis and does not require detection of cognate white blood cell antibodies. CONCLUSIONS: Clinicians should report all cases of posttransfusion pulmonary edema to the transfusion service so that further investigation can allow for classification of such cases as TRALI (Type I or Type II), ARDS, transfusion-associated circulatory overload (TACO), or TRALI or TACO cannot distinguish or an alternate diagnosis.

TACO and TRALI: biology, risk factors, and prevention strategies.

Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) are the leading causes of transfusion-related morbidity and mortality. These adverse events are characterized by acute pulmonary edema within 6 hours of a blood transfusion and have historically been difficult to study due to underrecognition and nonspecific diagnostic criteria. However, in the past decade, in vivo models and clinical studies utilizing active surveillance have advanced our understanding of their epidemiology and pathogenesis. With the adoption of mitigation strategies and patient blood management, the incidence of TRALI and TACO has decreased. Continued research to prevent and treat these severe cardiopulmonary events is focused on both the blood component and the transfusion recipient.

TRALI, una amenaza enmascarada: biología y fisiopatología / TRALI, a masked menace: biology and pathophysiology

El daño pulmonar agudo ocasionado por la transfusión o TRALI (por sus siglas en inglés), definido como la aparición de un distrés respiratorio agudo en un paciente recién transfundido, pasó de ser considerado una complicación infrecuente de la terapia transfusional a ser actualmente la principal causa de mortalidad por transfusión, según sistemas de hemovigilancia de Europa y Norteamérica. Su desarrollo en forma clínicamente reconocible se atribuye a la interacción entre factores dependientes de la unidad transfundida (tipo de componente, presencia de sustancias biológicamente activas, etc.) y el estado de las respuestas celulares en el receptor. La heterogeneidad en cuanto al cuadro clínico de los pacientes afectados,la variación en el volumen infundido, el tipo de componente implicado y el tiempo desde el inicio de la transfusión hasta la aparición de los síntomas, ha hecho evolucionar la explicación a la génesis de este evento adverso, en el afán de incluir los casos sin explicación mediante las distintas hipótesis. Dos interesantes acercamientos patogénicos resultan la teoría de dos golpes y el modelo basado en el umbral que impone la relación entre los distintos factores de riesgo. La naturaleza multicausal del TRALI y el sinnúmero de variables que pueden influir en su aparición y reconocimiento, continúan haciendo de este un reto médico importante en el contexto de la medicina transfusional, donde su mejor enfoque terapéutico sigue siendo el preventivo(AU)

Transfusion-related acute lung injury (TRALI) defined as the onset of an acute respiratory distress in a recently transfused patient, has passed from been considered a rare complication of transfusion therapy to be the leading cause of transfusion-associated death, as reported by hemovigilance systems in Europe and America. In a previous paper definition, epidemiology and some clinical aspects of TRALI are reviewed. Now we focused our efforts in reviewing the incompletely understood world of its pathogenesis. Clinically recognizable TRALI´s development depends on the interaction between risk factors from both the transfused component unit (as the kind of component and substances within it) and receiver patient´s cellular response. Heterogeneity of clinical features, transfused volumes, component type and time elapsed from the beginning of transfusion to the onset of symptoms have pushed the explanations for its genesis to evolve in an effort to include as much cases as the different hypotheses allowed. Two interesting approaches to TRALI´s pathogenesis are the two hit; theory and the threshold; model imposed by risk factors interactions. The large diversity of variables and causes which can influence its onset and clinical recognition continue to make it a real challenge for clinicians, mainly within transfusion medicine, where the best therapeutic approach available is prevention(AU)