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BACKGROUND: Systemic and pulmonary coagulopathy and inflammation are important characteristics of transfusion-related acute lung injury (TRALI). Whether microparticles that accumulate in transfused red blood cell concentrates (RBCs) have proinflammatory and procoagulant potential and contribute to adverse reactions of RBC transfusions is unclear. AIM: To investigate the ability of microparticles in stored RBCs to promote thrombin generation and induce human pulmonary microvascular endothelial cell (HMVEC) activation and damage. METHODS: The number and size of microparticles were determined by flow cytometric and nanoparticle tracking analyses, respectively. Thrombin generation and the intrinsic coagulation pathway were assayed by a calibrated automated thrombogram and by measuring activated partial thromboplastin time (aPTT), respectively. The expression of ICAM-1 and the release of cytokines by endothelial cells were detected by flow cytometric analyses. HMVEC damage was assessed by incubating lipopolysaccharide-activated endothelial cells with MP-primed polymorphonuclear neutrophils (PMNs). RESULTS: The size of the microparticles in the RBC supernatant was approximately 100-300 nm. Microparticles promoted thrombin generation in a dose-dependent manner and the aPTT was shortened. Depleting microparticles from the supernatant of RBCs stored for 35 days by either filtration or centrifugation significantly decreased the promotion of thrombin generation. The expression of ICAM-1 on HMVECs was increased significantly by incubation with isolated microparticles. Furthermore, microparticles induced the release of interleukin-6 (IL-6) and interleukin-8 (IL-8) from HMVECs. Microparticles induced lipopolysaccharide-activated HMVEC damage by priming PMNs, but this effect was prevented by inhibiting the PMNs respiratory burst with apocynin. CONCLUSION: Microparticles in stored RBCs promote thrombin generation, HMVEC activation and damage which may be involved in TRALI development.

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Introducción: La lesión pulmonar aguda (TRALI) y la sobrecarga circulatoria (TACO) son las principales causas de morbilidad y mortalidad relacionadas con la transfusión. La TRALI se presenta durante o después de las transfusiones de plasma y sus derivados, o por inmunoglobulinas en alta concentración intravenosa; se asocia a procesos sépticos, cirugías y transfusiones masivas. La TACO es la exacerbación de manifestaciones respiratorias en las primeras 6 horas postransfusión. Reporte caso: Paciente de sexo masculino de 38 días de vida, ingresó al servicio de urgencias con un cuadro clínico de 8 días de evolución, caracterizado por dificultad respiratoria dado por retracciones subcostales y aleteo nasal sin otro síntoma asociado, con antecedentes de importancia de prematuridad y bajo peso al nacer. El reporte de hemograma arrojó cifras compatibles con anemia severa, por lo que requirió transfusión de glóbulos rojos empaquetados desleucocitados. El paciente presentó un cuadro respiratorio alterado en un periodo menor a 6 horas, por lo que se descartaron causas infecciosas y finalmente se consideró cuadro compatible con TRALI. Conclusiones: Se debe considerar una lesión pulmonar aguda relacionada con una transfusión de sangre si se produce una insuficiencia respiratoria aguda durante o inmediatamente después de la infusión de hemoderivados que contienen plasma.

Introduction: Acute lung injury (TRALI) and circulatory overload (TACO) are the main causes of transfusion-related morbidity and mortality. TRALI occurs during or after transfusions of plasma or its derivatives, or by immunoglobulins in high intravenous concentration; it is associated with septic processes, surgeries, and massive transfusions. TACO is the exacerbation of respiratory manifestations in the first 6 hours post transfusion. Case report: A 38-day-old male was admitted to the emergency department with clinical symptoms experienced over the course of 8 days and characterized by respiratory distress due to subcostal retractions and nasal flaring with no other associated symptoms. Important antecedents included prematurity and low birth weight. The hemogram report showed figures compatible with anemia, which benefited from transfusion of packed red blood cells without leukocytes. In a period of less than 6 hours, the patient presented altered respiratory symptoms, practitioners ruled out infectious causes and finally considered clinical signs compatible with TRALI. Conclusion: Acute lung injury related to blood transfusion should be considered if acute respiratory failure occurs during or immediately after infusion of plasma-containing blood products.

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Resumen Las complicaciones pulmonares asociadas a la transfusión de hemoderivados son reacciones adversas graves y potencialmente mor tales. La Lesión Pulmonar Aguda Relacionada a Transfusión (TRALI), es una de las más frecuentes y con mayor mortalidad asociada. Es una entidad infradiagnosticada debido a su sintomatología inespecífica, a la ausencia de biomarcadores séricos específicos para su diagnóstico y a que aún la evidencia acerca de sus causas es heterogénea. El objetivo del presente artículo es documentar un caso clínico de TRALI y posteriormente, basados en la literatura actual, consolidar los aspectos fundamentales para la identificación oportuna de esta entidad y de dos diagnósticos diferenciales en el contexto de transfusión de hemoderivados y trauma: la Sobrecarga Circulatoria Asociada a Transfusión (TACO) y el Embolismo graso (EG). Así pues, se expone el caso clínico de una paciente adulto joven quien en el contexto de un politraumatismo requiere transfusión de hemoderivados, desarrollo de cuadro clínico compatible con TRALI; de esta manera, la discusión incluye aspectos epidemiológicos, fisiopatología, hallazgos imagenológicos y diagnóstico. Se logra concluir que es preciso poner a disposición de los profesionales del área de la salud literatura científica que favorezca la identificación de estas patologías con base en criterios clínicos, paraclínicos e imagenológicos, para así mismo, disminuir el riesgo de presentación y la mortalidad asociada.

Abstract Pulmonary complications associated with the transfusion of blood products are severe, potentially mortal adverse reactions. The transfusion-related acute lung injury (TRALI) is one of the most common and with higher associated mortality. It is an underdiagnosed entity due to its unspecified symptoms, the absence of diagnosis-specific serum biomarkers and the fact that the evidence about its causes is still heterogeneous. The objective of this article is to document a clinical case of TRALI and then, basing on the current literature, consolidate key aspects for the timely identification of this disease and of two differential diagnoses within the context of transfusion of blood products and trauma: the transfusion-associated circulatory overload (TACO) and fat embolism (FE). So, we pres ent the clinical case of a female young adult patient requiring a transfusion of blood products due to a polytraumatism whose clinical condition is compatible with TRALI; thus, the discussion includes epidemiological aspects, physiopathology, imaging findings and diagnosis. We conclude that it is necessary to provide healthcare professionals with scientific literature that favors the identification of these diseases basing on clinical, paraclinical and imaging criteria so as to reduce the risk of presentation and associated mortality.

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Transfusion-Related Acute Lung Injury (TRALI) is an immune-inflammatory lung pathology that manifests within the first 6-72 hours after administration of blood products. However, due to reduced awareness of TRALI, it continues to be an underreported and often underdiagnosed complication of transfusion therapy. We report a case of a 6-year-old girl with myelodysplastic syndrome and TRALI developed in the first hour after platelet transfusion. Diagnosis of TRALI is based on the exclusion of etiologic factors such as volume overload and cardiogenic pulmonary edema following transfusion. Symptoms responded to high-flow oxygen therapy, so intubation was not attempted and full recovery was achieved.

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RESUMEN La lesión pulmonar aguda producida por transfusión (TRALI, por sus siglas en inglés) es un síndrome clínico relativamente raro, que puede constituir una amenaza para la vida y que se caracteriza por insuficiencia respiratoria aguda, edema pulmonar no cardiogénico e hipotensión arterial durante o en el transcurso de 6 horas después de una transfusión de productos hemáticos. Aunque su verdadera incidencia es desconocida, se le ha atribuido 1 caso por cada 5000 transfusiones de cualquier producto hemático y ha sido una de las causas más frecuentes de muerte relacionada con la transfusión. Se presenta un caso de TRALI en el perioperatorio de una cirugía cardíaca con manifestaciones clínicas extremas, cuyo abordaje terapéutico fue extremadamente difícil para el equipo médico-quirúrgico, debido al contexto clínico en el que se presentó: cirugía cardíaca con circulación extracorpórea por diagnóstico de endocarditis infecciosa, lesión pulmonar previa y antecedente de otro tipo de reacción postransfusional.

ABSTRACT Transfusion-Related Acute Lung Injury (TRALI) is a relatively unusual, life-threatening clinical syndrome, characterized by acute respiratory failure, hypotension, and non-cardiogenic pulmonary edema during or within 6 hours after a blood product transfusion. Although its true incidence is unknown, it has been attributed one case per 5.000 transfusions of any blood product and has been one of the most frequent causes of transfusion-related death. We present a case of TRALI in the perioperative period of cardiac surgery with extreme clinical manifestations, whose therapeutic approach was extremely difficult for the medical-surgical team, due to its complex clinical setting: cardiac surgery with cardiopulmonary bypass due to diagnosis of infective endocarditis, previous lung injury and history of other post-transfusion reaction.

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ABSTRACT Case report of a patient with an immunodeficiency who demands regular replacement of intravenous immunoglobulin. She presented an episode of transfusion-related acute lung injury shortly after using an immunoglobulin product different than the one she usually received. The patient evolved with respiratory changes (hypoxia, dyspnea, change in pulmonary auscultation) minutes after the end of the infusion, and received non-invasive respiratory support. She was discharged after 36 hours with good outcome. The patient achieved full recovery, showing no further reactions in subsequent immunoglobulin infusions (no longer receiving the product that was used when she had the episode of transfusion-related acute lung injury). Although rare, this reaction is potentially serious and has no specific treatment other than supportive therapy. The literature is scarce regarding the risk of recurrence. The decision on whether to proceed with immunoglobulin therapy after this adverse effect should be analyzed individually, assessing the possible risks and benefits for the patient.

RESUMO Relato de caso de paciente com imunodeficiência que necessitava de reposição regular de imunoglobulina endovenosa. Ela apresentou um episódio de lesão pulmonar aguda relacionada à transfusão após uso de produto de imunoglobulina diferente daquele que recebia habitualmente. Evoluiu com alterações respiratórias (hipóxia, dispneia e alteração de ausculta pulmonar) minutos após o fim da infusão, necessitando de suporte respiratório não invasivo. A paciente recebeu alta hospitalar após 36 horas, com boa evolução. Obteve recuperação total dos sintomas, sem mais reações nas infusões subsequentes de imunoglobulina (sendo optado por não mais prescrever o produto que foi usado quando ocorreu o episódio de lesão pulmonar aguda relacionada à transfusão). Apesar de rara, essa reação é potencialmente grave, não possui tratamento específico além de terapia de suporte, e há pouca informação na literatura sobre o risco de recorrência. A decisão sobre o seguimento da terapia com imunoglobulina após esse efeito adverso deve ser analisada individualmente, avaliando os possíveis riscos e benefícios para o paciente.

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Resumen: Los recién nacidos, sobre todo los pretérminos, constituyen uno de los grupos que reciben más hemoderivados. Si bien se han disminuido los riesgos asociados a las transfusiones, aun así pueden presentarse complicaciones1,2. TRALI (Tranfusion Related Acute Lung Injury; en español: lesión pulmonar aguda asociada a transfusión) es una complicación poco frecuente pero potencialmente grave. Reconocida inicialmente en adultos, posteriormente se describieron casos en niños. En neonatos solamente existe un caso confirmado y publicado a nivel internacional. La incidencia real es incierta, dado el poco conocimiento de la patología y el subreporte. TRALI resultaría de un daño del endotelio vascular pulmonar, causando edema pulmonar y subsecuentemente hipoxemia. El tratamiento es de sostén3. La prevención se basa principalmente en la revisión permanente de las indicaciones de transfusión de hemoderivados y en la comunicación fluida con el equipo de hemoterapia para su diagnóstico oportuno. Se describe el caso clínico de un recién nacido prematuro que durante una transfusión de concentrado de glóbulos rojos presentó hipoxemia con necesidad de asistencia ventilatoria mecánica, alteraciones hemodinámicas y fiebre. Se descartaron procesos infecciosos. La radiografía de tórax mostró infiltrados compatibles con edema pulmonar. Se descartó la falla cardíaca. El tratamiento realizado fue de sostén de las funciones vitales. La evolución fue favorable en el correr de 72 horas. Se comunicó el caso al servicio de hemoterapia. A fin de prevenir transfusiones innecesarias es importante que cada servicio revise periódicamente sus guías de transfusión de hemoderivados.

Summary: Newborns, especially preterm newborns, are one of the age groups that receive the most hemoderivatives. Although the progress made in the field of hemotherapy have made it possible to reduce the risks associated with transfusions, in some cases there are still complications1,2. TRALI (transfusion related acute lung injury) is a rare but potentially serious complication. It was initially detected in adults, though cases were later described in children. In newborns, only one case has been confirmed and published globally. The actual incidence is uncertain, given the insufficient knowledge of the pathology and the fact that findings have been under reported. TRALI results from pulmonary vascular endothelial damage and causes pulmonary edema and subsequent hypoxemia. Treatment is observed with supportive treatment3. Prevention is mainly based on the permanent review of the hemoderivatives' transfusion directives and on the fluent communication among members of the hemotherapy medical team in order to ensure a timely diagnosis. The clinical case described below is that of a preterm newborn who, during a transfusion of red blood cell concentrate, showed hypoxemia, hemodynamic alterations and fever and required mechanical ventilatory support. Infectious processes were ruled out. Chest X-Rays showed infiltrates compatible with pulmonary edema. Heart failure was ruled out. The treatment was performed to support vital functions. The evolution was favorable in the course of 72 hours. The case was reported to the Hemotherapy Service. Blood component transfusion guidelines should be regularly reviewed in order to prevent the performance of unnecessary transfusions.

Resumo: Os recém-nascidos, especialmente os prematuros, são um dos grupos que recebem maior quantidade de hemoderivados. Embora os riscos associados tenham diminuído com o tempo, as transfusões ainda podem trazer complicações1,2. A TRALI (lesão pulmonar aguda relacionada à transfusão) é uma complicação rara, mas potencialmente grave. Inicialmente reconhecida em adultos, os casos foram posteriormente descritos em crianças. Em neonatos, há apenas um caso confirmado e publicado a nível internacional. A incidência real é incerta, dado que existe pouco conhecimento da patologia e é pouco relatada. A TRALI é provocada por danos no endotélio vascular pulmonar e causa edema pulmonar e subsequentemente hipoxemia. O tratamento é de suporte3. A prevenção baseia-se principalmente na revisão permanente das indicações de transfusão de hemoderivados e na comunicação fluida com a equipe de hemoterapia para o diagnóstico oportuno. Descrevemos o caso clínico de um recém-nascido prematuro que apresentou hipoxemia durante transfusão de concentrado de hemácias com necessidade de ventilação mecânica, alterações hemodinâmicas e febre. Descartamos processos infecciosos. A radiografia de tórax mostrou infiltrados compatíveis com edema pulmonar. Descartamos insuficiência cardíaca. Realizamos tratamento de suporte de funções vitais. A evolução foi favorável durante 72 horas. O caso foi relatado ao serviço de Hemoterapia. Para evitar transfusões desnecessárias, é importante que cada serviço revise periodicamente as diretrizes de transfusão de hemoderivados.

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La lesión pulmonar aguda producida por transfusión (TRALI) es un grave síndrome clínico que se presenta con hipoxemia aguda y edema pulmonar no cardiogénico dentro de las 6 h de una transfusión con productos sanguíneos. La incidencia reportada oscila entre 1 caso cada 5000-100.000 transfusiones. Se han propuesto dos teorías sobre su fisiopatología: inmunomediada y no inmune. El diagnóstico es clínico y el tratamiento, de sostén. La tasa de mortalidad puede llegar al 10%, y la morbilidad es alta. Presentamos un paciente que, durante el posoperatorio inmediato de una artrodesis posterior instrumentada por escoliosis, evoluciona con hipoxemia resistente. En la cirugía, requirió múltiples transfusiones con hemoderivados por sangrado activo, por lo que se arriba al diagnóstico de TRALI. Requirió asistencia respiratoria mecánica con altos parámetros por 72 h y sostén hemodinámico por bajo gasto cardíaco. La evolución fue favorable y recibió el alta hospitalaria a los 11 días, sin complicaciones(AU)

Transfusion-related acute lung injury (TRALI) is a serious clinical syndrome that occurs with acute hypoxemia and non-cardiogenic pulmonary edema within 6 hours of a transfusion with blood products. The reported incidence ranges from 1 case per 5,000-100,000 transfusions. Two theories have been proposed about its pathophysiology, an immune-mediated one and a non-immune one. The diagnosis is clinical, and the treatment is supportive. Mortality may reach 10%, with high morbidity. We report a patient who in the immediate postoperative period of posterior instrumented arthrodesis for scoliosis developed refractory hypoxemia. During surgery, he required multiple blood products transfusions due to active bleeding, so we diagnosed TRALI. The patient required mechanical ventilation with high parameters during 72 hours and hemodynamic support for low cardiac output. The outcome was favorable and he was discharged at day 11 without complications. (AU)

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Transfusion-related acute lung injury (TRALI) is a life-threatening intervention that develops within 6 hours of transfusion of one or more units of blood, and is an important cause of morbidity and mortality resulting from transfusion. It is necessary to dismiss other causes of acute lung injury (ALI), like sepsis, acute cardiogenic edema, acute respiratory distress syndrome (ARDS) or bacterial infection. There are two mechanisms that lead to the development of this syndrome: immune-mediated and no immune- mediated TRALI. A common theme among the experimental TRALI models is the central importance of neutrophils in mediating the early immune response, and lung vascular injury. Central clinical symptoms are dyspnea, tachypnea, tachycardia, cyanosis and pulmonary secretions, altogether with other hemodynamic alterations, such as hypotension and fever. Complementary to these clinical findings, long-term validated animal models for TRALI should allow the determination of the cellular targets for TRALI-inducing alloantibodies as well as delineation of the underlying pathogenic molecular mechanisms, and key molecular mediators of the pathology. Diagnostic criteria have been established and preventive measures have been implemented. These actions have contributed to the reduction in the overallnumber of fatalities. However, TRALI still remains a clinical problem. Any complication suspected of TRALI should immediately be reported.