Transfusion-related acute lung injury induced by human leucocyte antigen-II antibodies: Analysis of antibody typing and source.

BACKGROUND AND OBJECTIVES: To explore transfusion-related acute lung injury (TRALI) induced by human leucocyte antigen (HLA)-II antibodies, and to analyse antibody typing and source. MATERIALS AND METHODS: We retrospectively analysed the clinical symptoms and signs of two leukaemia patients with suspected TRALI from the same female donor. HLA phenotyping was performed on the two patients, the platelet donor, her husband and her two children. The HLA and human neutrophil antigen antibodies in the donor's plasma were identified. RESULTS: The clinical manifestations of two leukaemia patients were those of TRALI, and we treated them with timely ventilator support. A high titre of HLA-II antibodies was in the plasma of the platelet donor. The antibodies were directed at HLA-DRB3*03:01, HLA-DRB1*09:01, HLA-DRB1*12:02, HLA-DRB3*01:01 and HLA-DRB1*12:01:01G, which were specific to the HLA antigens of the two patients. High-resolution HLA genotyping suggested that the donor's HLA-II antibodies were derived from immune stimulation by the husband's antigens during pregnancy. CONCLUSIONS: This study described two cases of TRALI caused by HLA-II antibodies from the same female donor. Appropriate management of blood donors with a history of multiple pregnancies is crucial.

Adverse effects of microparticles on transfusion of stored red blood cell concentrates.

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.

Preservation of recipient plasma sphingosine-1-phosphate levels reduces transfusion-related acute lung injury.

Cold-stored (CS) platelets are once again being reintroduced for clinical use. Transfused CS platelets offer benefits over room temperature-stored (RTS) platelets such as increased hemostatic effects and prolongation of shelf-life. Despite these advantages little is known about their association with transfusion-related acute lung injury (TRALI). TRALI is associated with prolonged storage of RTS platelets and has a mortality of >15%. Determining the safety of CS platelets is important considering their proposed use in TRALI-vulnerable populations with inflammation such as surgical patients or patients with trauma. Donor platelet-derived ceramide causes TRALI, whereas donor platelet sphingosine-1-phosphate (S1P) is barrier protective. Females have higher plasma levels of S1P than males. Cold temperatures increase S1P levels in cells. Therefore, we hypothesized that female (donors or recipients) and/or CS platelets would decrease TRALI. To test this, we compared how male and female donor and recipient allogeneic platelet transfusions of CS (4°C) versus RTS (23°C) platelets stored for 5 days influence murine TRALI. Transfusion of CS platelets significantly reduced recipient lung tissue wet-to-dry ratios, bronchoalveolar lavage total protein, lung tissue myeloperoxidase enzyme activity, histological lung injury scores, and increased plasma sphingosine-1-phosphate (S1P) levels compared with RTS platelet transfusions. Female as opposed to male recipients had less TRALI and higher plasma S1P levels. Female donor mouse platelets had higher S1P levels than males. Mouse and human CS platelets had increased S1P levels compared with RTS platelets. Higher recipient plasma S1P levels appear protective considering females, and males receiving platelets from females or male CS platelets had less TRALI.NEW & NOTEWORTHY Transfusion-related acute lung injury (TRALI) though relatively rare represents a severe lung injury. The sphingolipid sphingosine-1-phosphate (S1P) regulates the severity of platelet-mediated TRALI. Female platelet transfusion recipient plasmas or stored platelets from female donors have higher S1P levels than males, which reduces TRALI. Cold storage of murine platelets preserves platelet-S1P, which reduces TRALI in platelet-transfused recipients.

Transfusion-Related acute lung injury (TRALI) caused by antibodies to HLA-DRB1* 07:01 and HLA-DQB1*02:02: A case report.

Transfusion-related acute lung injury (TRALI) is characterized by non-cardiogenic pulmonary edema and acute hypoxemia. There are few reports of HLA-II antibodies causing TRALI in China.

Lesión pulmonar aguda producida por transfusión (TRALI): Reporte de caso / Transfusion-induced acute lung injury (TRALI): Case report

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.

A Case Report of Inhaled Nitric Oxide for Transfusion-Related Acute Lung Injury.

Transfusion-related acute lung injury (TRALI) is an acute respiratory distress syndrome (ARDS) occurring during or within six hours after transfusion. On the other hand, while inhaled nitric oxide (iNO) temporarily improves arterial oxygenation with selective pulmonary vasodilation, there is no evidence of mortality reduction in ARDS. We herein report a case in which TRALI was diagnosed with severe hypoxemia during cardiovascular surgery, and extracorporeal membrane oxygenation (ECMO) was avoided by using iNO for respiratory management. Administering iNO to patients with acute respiratory failure may be useful as a bridging therapy to help patients recover. However, further evidence is needed before this treatment can become standard practise.

Extracellular vesicles: effectors of transfusion-related acute lung injury.

Respiratory transfusion reactions represent some of the most severe adverse reactions related to receiving blood products. Of those, transfusion-related acute lung injury (TRALI) is associated with elevated morbidity and mortality. TRALI is characterized by severe lung injury associated with inflammation, pulmonary neutrophil infiltration, lung barrier leak, and increased interstitial and airspace edema that cause respiratory failure. Presently, there are few means of detecting TRALI beyond clinical definitions based on physical examination and vital signs or preventing/treating TRALI beyond supportive care with oxygen and positive pressure ventilation. Mechanistically, TRALI is thought to be mediated by the culmination of two successive proinflammatory hits, which typically comprise a recipient factor (1st hit-e.g., systemic inflammatory conditions) and a donor factor (2nd hit-e.g., blood products containing pathogenic antibodies or bioactive lipids). An emerging concept in TRALI research is the contribution of extracellular vesicles (EVs) in mediating the first and/or second hit in TRALI. EVs are small, subcellular, membrane-bound vesicles that circulate in donor and recipient blood. Injurious EVs may be released by immune or vascular cells during inflammation, by infectious bacteria, or in blood products during storage, and can target the lung upon systemic dissemination. This review assesses emerging concepts such as how EVs: 1) mediate TRALI, 2) represent targets for therapeutic intervention to prevent or treat TRALI, and 3) serve as biochemical biomarkers facilitating TRALI diagnosis and detection in at-risk patients.

Anesthetic Management of a Patient With Massive Pulmonary Secretion During Cardiopulmonary Bypass Probably Due to Transfusion-Related Acute Lung Injury Type â ¡.

Transfusion-related acute lung injury (TRALI) is potentially life-threatening adverse reaction associated with blood transfusion and can induce perioperative pulmonary secretion. TRALI that develops during cardiopulmonary bypass (CPB) may be difficult to detect; however, the pathophysiology might manifest as derangements in CPB operations. A 79-year-old man was scheduled to undergo partial replacement of the aortic arch with CPB. Two units of red blood cells were loaded into the priming solution. Although the vital signs, including oxygenation, remained stable in the prebypass period, perfusionists noticed a decreasing trend in the venous reservoir level early in the CPB operations. The trend continued even during circulatory arrest with selective cerebral perfusion, resulting in the termination of the modified hemofiltration. Surgical procedures were accomplished uneventfully; however, a large amount of fluid was required to maintain the minimal reservoir level and CPB flow. The total fluid balance during CPB was +8,233 mL, which was quite unusual in our practice. When 800 mL of massive pulmonary secretion was detected before CPB withdrawal, the etiology could not be determined simultaneously; nonetheless, systemic vascular hyperpermeability was speculated to be the underlying pathophysiology. Our therapeutic approach following the treatment of acute respiratory distress syndrome contributed to halting the deterioration of lung injury. Although the pneumothorax developed on the first postoperative day, the patient was treated with the insertion of a chest drainage tube. Subsequently, the patient had a good course and was discharged without respiratory complications. In conclusion, massive pulmonary secretion, probably due to TRALI type II, was associated with derangements in CPB operations. Prompt identification of the underlying pathophysiology and appropriate intervention is crucial.

Transfusion-related acute lung injury under general anesthesia successfully treated with extracorporeal membrane oxygenation: A case report.

Transfusion-related acute lung injury (TRALI) is a serious complication of blood transfusion and can also develop severe hypoxemia. In TRALI cases with difficult blood oxygenation on mechanical ventilation support, temporary veno-venous extracorporeal membrane oxygenation support appears to maintain oxygen levels.

Update on transfusion-related acute lung injury: an overview of its pathogenesis and management.

Transfusion-related acute lung injury (TRALI) is a severe adverse event and a leading cause of transfusion-associated death. Its poor associated prognosis is due, in large part, to the current dearth of effective therapeutic strategies. Hence, an urgent need exists for effective management strategies for the prevention and treatment of associated lung edema. Recently, various preclinical and clinical studies have advanced the current knowledge regarding TRALI pathogenesis. In fact, the application of this knowledge to patient management has successfully decreased TRALI-associated morbidity. This article reviews the most relevant data and recent progress related to TRALI pathogenesis. Based on the existing two-hit theory, a novel three-step pathogenesis model composed of a priming step, pulmonary reaction, and effector phase is postulated to explain the process of TRALI. TRALI pathogenesis stage-specific management strategies based on clinical studies and preclinical models are summarized with an explication of their models of prevention and experimental drugs. The primary aim of this review is to provide useful insights regarding the underlying pathogenesis of TRALI to inform the development of preventive or therapeutic alternatives.

Standardized reporting of pulmonary transfusion complications: Development of a model reporting form and flowchart.

BACKGROUND: Pulmonary complications of blood transfusion, including transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), and transfusion-associated dyspnea, are generally underdiagnosed and under-reported. The international TRALI and TACO definitions have recently been updated. Currently, no standardized pulmonary transfusion reaction reporting form exists and most of the hemovigilance forms have not yet incorporated the updated definitions. We developed a harmonized reporting form, aimed at improved data collection on pulmonary transfusion reactions for hemovigilance and research purposes by developing a standardized model reporting form and flowchart. MATERIALS AND METHODS: Using a modified Delphi method among an international, multidisciplinary panel of 24 hemovigilance experts, detailed recommendations were developed for a standardized model reporting form for pulmonary complications of blood transfusion. Two Delphi rounds, including scoring systems, took place and several subsequent meetings were held to discuss issues and obtain consensus. Additionally, a flowchart was developed incorporating recently published redefinitions of pulmonary transfusion reactions. RESULTS: In total, 17 participants completed the first questionnaire (70.8% response rate) and 14 participants completed the second questionnaire (58.3% response rate). According to the results from the questionnaires, the standardized model reporting form was divided into various subcategories: general information, patient history and transfusion characteristics, reaction details, investigations, treatment and supportive care, narrative, and transfused product. CONCLUSION: In this article, we present the recommendations from a global group of experts in the hemovigilance field. The standardized model reporting form and flowchart provide an initiative that may improve data collected to address pulmonary transfusion reactions.

Patient Blood Management, Anemia, and Transfusion Optimization Across Surgical Specialties.

Patient blood management (PBM) is a systematic, evidence-based approach to improve patient outcomes by managing and preserving a patient's own blood and minimizing allogenic transfusion need and risk. According to the PBM approach, the goals of perioperative anemia management include early diagnosis, targeted treatment, blood conservation, restrictive transfusion except in cases of acute and massive hemorrhage, and ongoing quality assurance and research efforts to advance overall blood health.

Phenotyping and Genotyping of HNA: Prevalence, Risk of Alloimmunization, and HNA Incompatibilities in Indians.

Background: Antibodies to human neutrophil alloantigens (HNA) are involved in the pathophysiology of several clinical conditions including transfusion-related acute lung injury (TRALI), alloimmune and autoimmune neutropenia, and febrile nonhemolytic transfusion reactions leading to neutropenia. The cognate antigens are polymorphic structures expressed on several glycoproteins on the neutrophils, i.e., antigens HNA-1a, -1b, -1c, and -1d on Fc-γ-receptor IIIb; HNA-2 on CD177; HNA-3a and -3b on choline transporter-like protein 2; HNA-4a and -4b on CD11b/αM subunit of the αMß2-integrin (CD11b/CD18, Mac-1, CR3); and HNA-5a and -5b on αL-subunit (CD11a) of the αLß2 integrin (CD11a/CD18), leukocyte function associated molecule (LFA)-1. Currently, there is a lacuna of diagnostic methods for detection of HNA in India. This study aimed to determine the HNA frequencies in Indians, estimate the risk of alloimmunization, and prepare typed neutrophil panels, which can be used to detect HNA antibodies in neutropenia cases. Material and Methods: EDTA blood samples were collected from random 1,054 blood donors. HNA-2 was phenotyped on fresh EDTA samples using FITC labelled monoclonal anti-CD177 by flowcytometry. HNA-1 (FCGR3B) genotyping was carried out by DNA sequencing and PCR-RFLP. Antigens of HNA-3 (SLC44A2) and HNA-5 (ITGAL) were genotyped by PCR-RFLP using TaqαI and Bsp1286I restriction enzymes, respectively, while HNA-4 (ITGAM) was genotyped by PCR-SSP. Results: Allele frequencies of FCGR3B*01, FCGR3B*02, and FCGR3B*03 were found to be 0.433, 0.444, and 0.087, respectively. FCGR3B*01+*02+*03- was the most common genotype (33.78%). Ten individuals showed deficiency of FCGR3B individuals, while 23 showed hyperexpression, i.e., FCGR3B*01+*02+*03+. FCGR3B*04and *05 occurred with a frequency of 0.002 and 0.024. HNA-2 was found to be a high frequency antigen occurring in 98.8% population. Four percent individuals showed atypical expression of CD177 on their neutrophils. Allele frequencies of SLC44A2*01 and SLC44A2*02were 0.812 and 0.188, respectively, and that of ITGAM*01, ITGAM*02, ITGAL*01, and ITGAL*02 were 0.9546, 0.0454, 0.2372, and 0.7628, respectively. Conclusion: This is the first study in India to report the frequencies of HNA among blood donors. Typed neutrophil panels identified in the present study will enable us to investigate suspected cases of immune neutropenia in future.

Transfusion-Related Acute Lung Injury Caused by HLA-II Antibodies: A Case Report.

OBJECTIVE: The aim of this study was to retrospectively analyze the etiology of a case of suspected transfusion-related acute lung injury (TRALI) occurring after blood transfusion. METHODS: The clinical symptoms, signs, imaging examinations, and laboratory test results of a patient with suspected TRALI after blood transfusion were retrospectively analyzed, and human leukocyte antigen (HLA) genotyping of the patient and HLA antibodies of the plasma donors were performed. RESULTS: The clinical manifestations of the patient were consistent with those of TRALI after blood transfusion. This TRALI was treated by timely ventilator support. The patient results of high-resolution HLA genotyping were HLA-A* 01:01, 11:01; HLA-B* 15:02, 37:01; HLA-C* 06:02, 08:01; DRB1* 10:01, 12:02; DRB3* 03:01, 03:01; DQA1* 01:05, 06:01; DQB1* 03:01, 05:01; DPA1* 01:03, 02:01; and DPB1* 02:01, 09:01. Of the 6 plasma donors tested, 3 were found to have HLA-II antibodies, which were HLA-DPA1*01:03, HLA-DQB1*03:01, and HLA-DQB1*03:01 antibodies. CONCLUSION: We described a case of TRALI caused by HLA-DQB1*03:01 antibody and DPA1*01:03 antibody.

Platelets play a dual role in the pathophysiology of transfusion-related acute lung injury.

Platelets are increasingly recognized as key regulators of inflammatory and immune responses, through their interaction with endothelium and immune cells. Therefore they might have a role in transfusion-related acute lung injury (TRALI), in which endothelial cells and neutrophils are the key players. In this study, by a classic TRALI animal model, combining a custom-designed system for intravital confocal microscopy of pulmonary microvasculature and a platelet tracking technique, we found that thrombin-activated platelets transfusion aggravated TRALI while resting platelets transfusion alleviated TRALI. Promoting endogenous platelets activation also aggravated TRALI while inhibiting endogenous platelets activation alleviated TRALI. Activated platelets interfered with the stability of endothelial barrier function while resting platelets modulated the activation of neutrophils. Anti-thrombin could alleviate TRALI, which was not reproduced upon anti-GPIIbIIIa or anti-P-selectin In conclusion, platelets might play a dual role (protective and pathogenic) in TRALI, the balance between the two roles is highly dependent on whether platelets are activated by thrombin or not. This might explain the conflicting results of previous researches studying the contribution of platelets in TRALI by platelet depletion technology, in which the induction of TRALI and the condition of animals were different, hence the state of platelets during TRALI was different. Moreover, anti-platelet-activation (such as anti-thrombin) might be a better approach than anti-activated-platelets (such as anti-P-selectin) to search for potential therapies in TRALI. Considering the involvement of thrombin-activated platelets in TRALI, anti-thrombin might be needed when blood component transfusion is performed.

Crosstalk between neutrophil extracellular traps and immune regulation: insights into pathobiology and therapeutic implications of transfusion-related acute lung injury.

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-associated death, occurring during or within 6 hours after transfusion. Reports indicate that TRALI can be categorized as having or lacking acute respiratory distress syndrome (ARDS) risk factors. There are two types of TRALI in terms of its pathogenesis: antibody-mediated and non-antibody-mediated. The key initiation steps involve the priming and activation of neutrophils, with neutrophil extracellular traps (NETs) being established as effector molecules formed by activated neutrophils in response to various stimuli. These NETs contribute to the production and release of reactive oxygen species (ROS) and participate in the destruction of pulmonary vascular endothelial cells. The significant role of NETs in TRALI is well recognized, offering a potential pathway for TRALI treatment. Moreover, platelets, macrophages, endothelial cells, and complements have been identified as promoters of NET formation. Concurrently, studies have demonstrated that the storage of platelets and concentrated red blood cells (RBC) can induce TRALI through bioactive lipids. In this article, recent clinical and pre-clinical studies on the pathophysiology and pathogenesis of TRALI are reviewed to further illuminate the mechanism through which NETs induce TRALI. This review aims to propose new therapeutic strategies for TRALI, with the hope of effectively improving its poor prognosis.

Case report: Suspected transfusion-related acute lung injury type II in a child with refractory systemic juvenile idiopathic arthritis complicated by macrophage activation syndrome.

Introduction: Transfusion-related acute lung injury is a rare but potentially fatal complication, which may appear during or post-transfusion of blood products. Patients with macrophage activation syndrome, a serious life-threatening complication associated with systemic juvenile idiopathic arthritis, often require transfusion or administration of blood products for correction of cytopenia, coagulopathy and hypofibrinogenemia. Case report: A 6-year-old girl with a past medical history of systemic juvenile idiopathic arthritis had the first relapse of the disease during which she developed macrophage activation syndrome. During this life-threatening complication, she received a second dose of whole blood derived filtered and irradiated platelets from a single male donor due to profound thrombocytopenia. Approximately one hour post-infusion, the patient developed progressive dyspnea, hypoxemia and bilateral pulmonary edema. She was promptly intubated and placed on mechanical ventilation for 40 h. Clinical, laboratory and radiological findings, as well as the success of supportive ventilation therapy were highly suggestive of transfusion-related acute lung injury, a life-threatening complication that occurs within six hours of blood component transfusion. Blood immunology showed no presence of anti-human neutrophil antigen and anti-leukocyte antigen class I and class II antibodies in the donor's or patient's plasma. Conclusion: To the best of our knowledge, we report the first case of a child with systemic juvenile idiopathic arthritis complicated with macrophage activation syndrome who developed type II transfusion-related acute lung injury following platelet transfusion. It is important to consider transfusion-related acute lung injury in transfusion settings in these children and apply critical and restrictive approach for platelet transfusion.

Transfusion-Related Acute Lung Injury (TRALI) in Postoperative Anesthesia Care Unit (PACU) After One Unit of Platelets: A Case Report.

Transfusion-related acute lung injury (TRALI) following transfusion of all plasma-containing blood products is a rare but serious syndrome characterized by the acute onset of non-cardiogenic pulmonary edema with severe hypoxemia with or without symptoms of hypotension, pinkish frothy secretions, fever, and cyanosis. In this report, we present a case of a 66-year-old female with a medical history significant for hypertension, hyperlipidemia, hepatitis C, liver cirrhosis, tobacco use disorder, metastatic spindle cell carcinoma of the lung status post chemotherapy who developed TRALI after administration of one unit of platelets. Although a rare occurrence, there can be a considerable risk of TRALI following transfusion of all plasma-containing blood products and there is great importance in considering each patient's risk factors for TRALI development prior to blood product administration.

Aged versus fresh autologous platelet transfusion in a two-hit healthy volunteer model of transfusion-related acute lung injury.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is a severe complication of blood transfusion that is thought of as a two-hit event: first the underlying patient condition (e.g., sepsis), and then the transfusion. Transfusion factors include human leukocyte antigen antibodies or biologic response modifiers (BRMs) accumulating during storage. Preclinical studies show an increased TRALI risk with longer stored platelets, clinical studies are conflicting. We aim to discover whether longer platelet concentrate (PC) storage time increases TRALI risk in a controlled human experiment. STUDY DESIGN AND METHODS: In a randomized controlled trial, 18 healthy male volunteers received a first hit of experimental endotoxemia (2 ng/kg lipopolysaccharide), and a second hit of fresh (2-day old) or aged (7-day old) autologous PC, or physiological saline. After 6 h, changes in TRALI pathways were determined using spirometry, chest X-ray, and bronchoalveolar lavage (BAL). RESULTS: All subjects reacted adequately to lipopolysaccharide infusion and satisfied SIRS criteria (increased pulse [>90/min] and temperature [>38°C]). There were no differences between the saline, fresh, and aged PC groups in BAL-fluid protein (95 ± 33 µg/ml; 83 ± 21 µg/ml and 104 ± 29 µg/ml, respectively) and relative neutrophil count (1.5 ± 0.5%; 1.9 ± 0.8% and 1.3 ± 0.8%, respectively), nor in inflammatory BAL-fluid BRMs (Interleukin-6, CXCL8, TNFα , and myeloperoxidase), clinical respiratory parameters, and spirometry results. All chest X-rays were normal. CONCLUSIONS: In a human endotoxemia model of autologous platelet transfusion, with an adequate first hit and platelet storage lesion, transfusion of 7-day-old PC does not increase pulmonary inflammation compared with 2-day-old PC.

Chronicle of Hypoxemia: Transfusion-Associated Circulatory Overload Versus Transfusion-Related Acute Lung Injury.

The preeminent causes of blood transfusion-related morbidity and mortality are transfusion-associated circulatory overload (TACO) and transfusion-related acute lung injury (TRALI). These occur within hours of blood transfusion and lead to acute respiratory distress. The differentiation between TACO and TRALI has always been a great challenge in the context of underlying etiology, whether it is volume overload or lung injury, or both. This is a case report of a 64-year-old female with multiple comorbidities, who was brought to the emergency department with generalized weakness. She was hemodynamically unstable and encephalopathic. Her hemoglobin was 6.5 gm/dl with no active evidence of bleeding. She was started on a norepinephrine drip and one unit of packed red blood cells was transfused. A few hours post-transfusion, she became extremely tachypneic and hypoxic. A chest x-ray post-transfusion showed diffuse bilateral fluffy alveolar infiltrates and the N-terminal (NT)-pro hormone Brain Natriuretic Peptide (NT-proBNP) was significantly elevated. The transfusion reaction workup was negative. Due to worsening hypoxia, she required a rapid transition from non-invasive to invasive mechanical ventilation. The chronology of this case report depicts a unique presentation of acute respiratory distress and the course of hypoxemia.