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.

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.

Study on transfusion-related acute lung injury caused by HLA-Ⅱ antibody / 中国输血杂志

【Objective】 To explore the risk factors of transfusion-related acute lung injury (TRALI). 【Methods】 The clinical symptoms, signs, imaging examinations, and laboratory test results of two patients with TRALI after blood transfusion were retrospectively analyzed, and human leukocyte antigen (HLA) genotyping of the patient and HLA antibodies typing of the plasma donors were performed. 【Results】 The clinical manifestations and laboratory parameters of two patients were consistent with those of TRALI after blood transfusion. After timely clinical respiratory support treatment, all patients were improved. Blood donors produced high titers of HLA-Ⅱ antibodies after pregnancy, including antibodies that specifically recognize the patient′s HLA antigen. 【Conclusion】 Two patients developed TRALI after platelet transfusion from a female blood donor, which was caused by HLA-Ⅱ antibodies.

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.

Tirofiban interferes with antibody-mediated transfusion-related acute lung injury by inhibiting platelet-neutrophil binding / 中国输血杂志

【Objective】 To explore the feasibility of tirofiban, a platelet surface glycoprotein (GP)Ⅱb/Ⅲa receptor antagonist intervene in transfusion-related acute lung injury (TRALI), by inhibiting platelet activation and by preventing platelet and neutrophil binding to form aggregates. 【Methods】 1) Fifty wild-type male Balb/c mice, aged 8 to 10 weeks, were randomly divided into TRALI, normal, tirofiban TRALI intervention, isotype control and tirofiban normal intervention groups. In the TRALI model, tirofiban TRALI intervention and isotype control groups, each mouse was injected intraperitoneally with lipopolysaccharide (LPS) 0.1 mg/kg, and after 18 h with 4.5 mg/kg anti-MHC-I or IgG2a isotype control antibody, in which 0.5 μg/g tirofiban was injected 30 min before anti-MHC-I injection, and was labeled as tirofiban TRALI intervention. The group without any treatment was set as normal group. The tirofiban normal intervention group was injected with only 0.5 μg/g tirofiban into the tail vein, 30 min before the injection of anti-MHC-I. 2) After antibody injection, the mice were observed for 2 h, then executed with their lungs removed, and the extent of lung injury and the intervention effect of tirofiban were analyzed by comparing the differences in lung dry to wet ratio, total protein, myeloperoxidase (MPO), inflammatory factors and quantitative results of HE staining. The platelet activation level in whole blood and immunofluorescence (IF) quantification of platelet and neutrophil fluorescence were detected by flow cytometry to analyze the mechanism of tirofiban on TRALI. 【Results】 1) The indexes of lung injury in the tirofiban TRALI intervention group and TRALI model group for HE staining were 0.663 3±0.141 9 vs. 0.173 3±0.120 4 (P<0.05), respectively; 2) Platelet activation levels(%)in whole blood in the TRALI group, normal group and tirofiban TRALI intervention group were 22.87±9.943 vs 5.070±2.234 vs 5.767±3.224(P<0.05), respectively. 3) The mean fluorescence density of platelet neutrophil aggregates for IF detection in the tirofiban intervention group and TRALI model group was 21.89±3.536 vs. 32.77±0.9624 (P<0.05). 【Conclusion】 The platelet GP Ⅱ b/Ⅲa-specific inhibitor tirofiban inhibited platelet-neutrophil binding in mice, thus could possibly intervene in TRALI.

Function of platelet-derived extracellular vesicles in adverse reactions to blood transfusion / 中国输血杂志

Recent studies have shown that a series of structural and functional changes would occur during the process of platelet collection, storage and transfusion. The storage of platelets would induce the production of extracellular vesicles. During the process of platelet transfusion, extracellular vesicles play a critical role by carrying diverse substances under various pathophysiological conditions, which causes adverse reactions to blood transfusion. Ceramide and soluble CD40L (sCD40L) carried by platelet-derived extracellular vesicles may lead to transfusion-related acute lung injury (TRALI). Extracellular vesicles containing mtDNA are considered as damage-associated molecular patterns (DAMPs), which can mediate local and systemic inflammation and promote inflammation through interactions with leukocytes and monocytes. Platelet derived extracellular vesicles contain lots of procoagulant substances, which are considered as prethrombotic substances. The RNA of varying species or content carried by vesicles during the process of platelet storage may also related to the occurrence of adverse reactions to blood transfusion.

Potential of modulating fibrinolytic activity in intervention of transfusion-related acute lung injury / 中国输血杂志

Transfusion-related acute lung injury (TRALI), with clinical manifestation, diagnosis and pathological mechanism consistent with acute lung injury(ALI), belongs to a sub-category of ALI. Excessive deposition of fibrin in lung is one of the characteristic of ALI, and reversing fibrin formation is of great significance to intervene ALI. The decrease of fibrinolytic activity is one of the important causes of excessive deposition of fibrin in lung, and also the important pathological feature of TRALI. This article discusses the potential of modulating fibrinolytic activity to intervene TRALI from the perspective of regulating the effectiveness of fibrinolytic activity to intervene ALI.

Microparticles in red cell concentrates prime polymorphonuclear neutrophils and cause acute lung injury in a two-event mouse model.

Red cell-derived microparticles (RMPs) are potential mediators of transfusion-related acute lung injury (TRALI). The aim of this study was to investigate the effects of microparticles present in red cell concentrates (RCC) on polymorphonuclear neutrophil (PMN) respiratory burst and acute lung injury (ALI) in mice. Microparticles (MPs) in RCC supernatant were quantified using flow cytometry. The priming activity of either isolated MPs or RCC supernatant toward human PMN was measured in vitro. Mice were injected with lipopolysaccharide (LPS), followed by an infusion of either isolated MPs or heat-treated RCC supernatant. The lungs were harvested to assess myeloperoxidase (MPO) activity, histology and pulmonary edema. Protein content in bronchoalveolar lavage fluid (BALF) was measured. The number of RMPs increased significantly during storage. Both isolated MPs and the supernatants from RCCs that had been stored for 28 and 35days effectively primed the PMN respiratory burst. The infusion of isolated MPs or supernatants that had been stored for >28days into LPS-treated mice caused ALI. The filtered supernatant resulted in significantly ameliorated mouse ALI. MPs that accumulate during RCC storage prime the PMN respiratory burst and cause ALI in a two-event mouse model.

Rare antibody-associated hemolytic transfusion reaction and transfusion-related acute lung injury: a case report.

BACKGROUND: Hemolytic transfusion reactions and transfusion-related acute lung injury (TRALI) are life-threatening complications associated with the transfusion of blood products. Hemorrhage is one of the most common surgical complications and the risk of bleeding is particularly acute in patients with hematologic deficiencies. Management of surgical bleeding can be divided into two phases. The first phase centers on immediate control of acute bleeding and the second phase focuses on keeping the patient stable and on reducing the sequelae associated with blood transfusions and blood loss. CASE PRESENTATION: We present the case of a 53-year-old woman with long-standing immune thrombocytopenia who underwent repair of a symptomatic ventral hernia. On post-operative day one the patient developed hemoperitoneum, requiring exploratory laparotomy and massive transfusion of blood products. The patient's recovery was complicated by consistently low hemoglobin, hematocrit and platelets, prompting frequent transfusion of additional blood products. Shortly after activation of the massive transfusion protocol, the patient developed TRALI. Compounding the situation, on post-operative day sixteen the patient's serum started to show hemolysis: lactate dehydrogenase (LDH) levels rose to 1,845 IU/L, with haptoglobin at less than 5.8 mg/dL and with a high reticulocyte count (4.38%). Previous testing had shown that the patient was positive for most major antigens implicated in antibody formation and was only producing anti-E and anti-K antibodies (considered for all transfusions). Initial pre- and post-transfusion direct antiglobulin tests (DAT) were indeed negative. However, repeat DATs in the days following the noted serum changes were consistent with new allo-antibody formation. These findings prompted immediate withholding of all blood products and a thorough blood bank work up. Despite strong evidence for new allo-antibody formation, no specific known antibody could be identified. The patient recover well when blood products were withheld. DISCUSSION: We present the case of a 53-year-old woman with long-standing immune thrombocytopenia who underwent repair of a symptomatic ventral hernia. On post-operative day one the patient developed hemoperitoneum, requiring exploratory laparotomy and massive transfusion of blood products. The patient's recovery was complicated by consistently low hemoglobin, hematocrit and platelets, prompting frequent transfusion of additional blood products. Shortly after activation of the massive transfusion protocol, the patient developed TRALI. Compounding the situation, on post-operative day sixteen the patient's serum started to show hemolysis: lactate dehydrogenase (LDH) levels rose to 1,845 IU/L, with haptoglobin at less than 5.8 mg/dL and with a high reticulocyte count (4.38%). Previous testing had shown that the patient was positive for most major antigens implicated in antibody formation and was only producing anti-E and anti-K antibodies (considered for all transfusions). Initial pre- and post-transfusion direct antiglobulin tests (DAT) were indeed negative. However, repeat DATs in the days following the noted serum changes were consistent with new allo-antibody formation. These findings prompted immediate withholding of all blood products and a thorough blood bank work up. Despite strong evidence for new allo-antibody formation, no specific known antibody could be identified. The patient recover well when blood products were withheld. Suspicion for hemolytic transfusion reactions should be high in patients with prior allo-antibody formation; these may present as acute hemolysis or as a delayed hemolytic transfusion reaction. Withholding blood products from these patients until compatible products have been identified is recommended. Moreover, TRALI is the leading cause of transfusion-related fatalities and should always be considered in transfusion settings. CONCLUSIONS: Suspicion for hemolytic transfusion reactions should be high in patients with prior allo-antibody formation; these may present as acute hemolysis or as a delayed hemolytic transfusion reaction. Withholding blood products from these patients until compatible products have been identified is recommended. Moreover, TRALI is the leading cause of transfusion-related fatalities and should always be considered in transfusion settings.

Transfusion Related Acute Lung Injury (TRALI): A Single Institution Experience of 15 Years.

Transfusion related acute Lung injury (TRALI) though a serious blood transfusion reaction with a fatality rate of 5-25 % presents with acute respiratory distress with hypoxaemia and noncardiac pulmonary oedema within 6 h of transfusion. In non fatal cases, it may resolve within 72 h or earlier. Although reported with an incidence of 1:5000, its true occurrence is rather unknown. Pathogenesis is believed to be related to sequestration and adhesion of neutrophils to the pulmonary capillary endothelium and its activation leading to its destruction and leaks. The patient's underlying condition, anti-neutrophil antibody in the transfused donor plasma and certain lipids that accumulate in routinely stores blood and components are important in its aetiopathogenesis. Patient's predisposing conditions include haematological malignancy, major surgery (especially cardiac), trauma and infections. The more commonly incriminated products include fresh frozen plasma (FFP), platelets (whole blood derived and apheresis), whole blood and Packed RBC. Occasional cases involving cryoprecipitate and Intravenous immunoglobulin (IVig) have also been reported. We present a 15 year single institution experience of TRALI, during which we observed 9 cases among 170,871 transfusions, giving an incidence of 1:19,000. We did not encounter cases of haematological malignancy or cardiac surgery in our TRALI patients. Among the blood products, that could be related to TRALI in our patients included solitary cases receiving cryoprecipitate, IVIg, and recombinant Factor VII apart from platelets and FFP. All patients were treated with oxygen support. Six patients required mechanical ventilation. Off label hydrocortisone was given to all patients. There were no cases of fatality among our patients.

A Case Report of Transfusion-Related Acute Lung Injury Induced in the Patient with HLA Antibody after Fresh Frozen Plasma Transfusion / 대한수혈학회지

Development of transfusion-related acute lung injury (TRALI), a non-cardiogenic pulmonary edema, after blood transfusion, is a rare but potentially leading cause of mortality from blood transfusion. We report on a case of TRALI in a 51-year male with acute calculous cholecystitis and liver cirrhosis. As preoperative treatment, he was given ten units of fresh frozen plasma (FFP) for 3 days before the operation. During the transfusion of the 10th unit of FFP, he experienced a sudden onset of hemoptysis, tachypnea, tachycardia, and cyanosis. Bilateral pulmonary infiltration not observed on the chest X-ray at the visit was newly developed. There was no evidence of volume overload but severe hypoxemia. Blood transfusion was stopped and he recovered fully after 8 days of oxygen therapy through a nasal cannula. Although HLA and HNA antibodies were not detected in the donor's blood, HLA antibodies (A2, B57, B58) were detected in the patient's blood. We reported this meaningful case of TRALI that occurred after transfusion of only fresh frozen plasma which did not contain human leukocyte antibody in a patient with HLA antibody.

Human Neutrophil Alloantigen-3a Alloimmunization among Pregnant Korean Women / 대한수혈학회지

BACKGROUND: Alloantibodies against human neutrophil alloantigen (HNA)-3a are associated with severe and fatal transfusion related acute lung injury (TRALI). HNA-3 genotyping and HNA-3a antibody (Ab) identification are essential to diagnosis and prevention of TRALI caused by HNA-3a Ab. However there had been no laboratory for HNA-3a Ab identification in Korea. The aims of this study were to establish the HNA-3a Ab test in Korea and to estimate the incidence of HNA-3a alloimmunization among pregnant Korean women. METHODS: HNA-3a homozygotes and HNA-3b homozygotes were identified by HNA-3 genotyping. Three HNA-3a homozygotes and three HNA-3b homozygotes are included in the granulocytes panel, which consisted of 10 donors for granulocytes. Sera from 650 pregnant Korean women were tested for granulocyte Ab using a mixed passive hemagglutination assay (MPHA). When a HNA-3a Ab was detected, the woman's HNA-3 was typed to support her HNA-3a alloimmunization. RESULTS: MPHA showed positive reactions in the sera from 26 women (4.0%, 26/650). HLA Abs were detected in 18 women (2.8%, 18/650), among whom HNA Abs were identified simultaneously in 7 women. Granulocyte Abs were detected in sera from 15 women (2.3%, 15/650). The incidence of HNA-3a, HNA-1b, HNA-1a, HNA-2a, and unidentified HNA Abs among pregnant Korean women was 0.77% (5/650), 0.77% (5/650), 0.62% (4/650), 0.15 (1/650), and 0.31% (2/650), respectively. CONCLUSION: In this study, we established the HNA-3a Ab test using MPHA for diagnosis and prevention of TRALI caused by HNA-3a Ab. The incidence of HNA-3a Ab in pregnant Korean women was 0.77% (5/650).

A case of transfusion-related acute lung injury induced by anti-human leukocyte antigen antibodies in acute leukemia.

Transfusion-related acute lung injury (TRALI) is a noncardiogenic pulmonary edema that occurs during or within 6 hours after transfusion. Risk factors for TRALI, which is relatively common in critically ill patients, include recent surgery, hematologic malignancy, and sepsis. Here, we report a case of TRALI induced by anti-human leukocyte antigen (anti-HLA) class II antibodies (HLA-DR) occurring after transfusion of platelet concentrates in a patient with acute leukemia. Although most patients with TRALI show improvement within 48-96 hours, our patient's condition rapidly worsened, and he did not respond to supportive treatment. TRALI is a relatively common and serious adverse transfusion reaction that requires prompt diagnosis and management.

A case of transfusion-related acute lung injury induced by anti-human leukocyte antigen antibodies in acute leukemia

Transfusion-related acute lung injury (TRALI) is a noncardiogenic pulmonary edema that occurs during or within 6 hours after transfusion. Risk factors for TRALI, which is relatively common in critically ill patients, include recent surgery, hematologic malignancy, and sepsis. Here, we report a case of TRALI induced by anti-human leukocyte antigen (anti-HLA) class II antibodies (HLA-DR) occurring after transfusion of platelet concentrates in a patient with acute leukemia. Although most patients with TRALI show improvement within 48-96 hours, our patient's condition rapidly worsened, and he did not respond to supportive treatment. TRALI is a relatively common and serious adverse transfusion reaction that requires prompt diagnosis and management.

Two cases of transfusion-related acute lung injury triggered by HLA and anti-HLA antibody reaction.

Transfusion-related acute lung injury (TRALI) is a serious adverse transfusion reaction that is presented as acute hypoxemia and non-cardiogenic pulmonary edema, which develops during or within 6 hr of transfusion. Major pathogenesis of TRALI is known to be related with anti-HLA class I, anti-HLA class II, or anti-HNA in donor's plasma. However, anti-HLA or anti-HNA in recipient against transfused donor's leukocyte antigens also cause TRALI in minor pathogenesis and which comprises about 10% of TRALI. Published reports of TRALI are relatively rare in Korea. In our cases, both patients presented with dyspnea and hypoxemia during transfusion of packed red blood cells and showed findings of bilateral pulmonary infiltrations at chest radiography. Findings of patients' anti-HLA antibodies and recipients' HLA concordance indicate that minor pathogenesis may be not as infrequent as we'd expected before. In addition, second case showed that anti-HLA class II antibodies could be responsible for immunopathogenic mechanisms, alone.

Two Cases of Transfusion-related Acute Lung Injury Triggered by HLA and Anti-HLA Antibody Reaction

Transfusion-related acute lung injury (TRALI) is a serious adverse transfusion reaction that is presented as acute hypoxemia and non-cardiogenic pulmonary edema, which develops during or within 6 hr of transfusion. Major pathogenesis of TRALI is known to be related with anti-HLA class I, anti-HLA class II, or anti-HNA in donor's plasma. However, anti-HLA or anti-HNA in recipient against transfused donor's leukocyte antigens also cause TRALI in minor pathogenesis and which comprises about 10% of TRALI. Published reports of TRALI are relatively rare in Korea. In our cases, both patients presented with dyspnea and hypoxemia during transfusion of packed red blood cells and showed findings of bilateral pulmonary infiltrations at chest radiography. Findings of patients' anti-HLA antibodies and recipients' HLA concordance indicate that minor pathogenesis may be not as infrequent as we'd expected before. In addition, second case showed that anti-HLA class II antibodies could be responsible for immunopathogenic mechanisms, alone.

Transfusion-Related Acute Lung Injury (TRALI) in Patients with Aneurysmal Subarachnoid Hemorrhage (SAH) / 대한뇌혈관외과학회지

OBJECTIVE: Transfusion-related acute lung injury (TRALI) is a poorly understood, but life-threatening complication after transfusion of blood components. The present study was conducted to identify the incidence of TRALI in patients with aneurysmal subarachnoid hemorrhage (SAH) as well as to determine the risk factors for TRALI. METHODS: This retrospective study was carried out on our institute, during the period of Jan. 2006 and Dec. 2008 to a total of 237 patients who underwent microsurgical treatment for aneurysmal SAH. In this time period, 154 patients were finally enrolled in this study. Patients' demographics, clinical and radiographic factors relevant to the aneurysms and SAH, and parameters regarding transfusion were analyzed and compared. RESULTS: A total of 9 patients had TRALI among a total of 154 patients. The incidence of TRALI was 0.01% (9 in 836) for all transfused blood component, and 0.06% (9 in 154) for all transfused patients. Statistical analysis showed that Fisher grade III and IV (OR, 1.88; 95% CI, 1.13-3.07) and total amount of transfused units exceeding 1,200cc (OR 1.72; 95% CI, 1.22-2.65) were associated with the development of TRALI. On the other hand, sex, poor Hunt-Hess Grade (IV and V), preoperative hemoglobin less than 13, postoperative hemoglobin less than 11, use of volume expander, premorbid disease (hypertension, diabetes) were not associated with TRALI. CONCLUSIONS: The results of present study indicate that large amount SAH and transfusion of blood components more than 1,200cc are risk factors for the development of TRALI. Prospectively designed study with a larger cohort is mandated to confirm the etiology and risk factors of TRALI in stroke practice.

Transfusion related acute lung injury occurred in HLA half-matched hematopoietic stem cell transplantation:a case report and literature review / 中国输血杂志

Objective To clarify the risk,treatment and preventive measurement of transfusion related acute lung injury (TRALI) occurred in HLA half-matched hematopoietic stem cell transplantation. Methods A case of TRALI occurred in HLA half-matched hematopoietic stem cell transplantation was analyzed,including the clinical characteristics,the laboratory and instrumental examination,the treatment measure and prognosis,and then the associated literature was reviewed.Results Owing to the blood products(fresh platelet) transfusion during transplantation,the patient got TRALI. And after active rescue,the patient eventually died due to the worsen condition.Conclusion The risk of TRALI is very high in HLA half-matched hematopoietic stem cell transplantation since the blood products transfusion is inevitable,so the effective and timely treatment and preventive measurement are necessary.

A Case of Transfusion-related Acute Lung Injury / 대한수혈학회지

Transfusion-related acute lung injury (TRALI) is defined as a new episode of acute lung injury that occurs during or within 6 hours of a completed transfusion, which has been the leading cause of transfusion-related death. We report a case of TRALI in a 63-year old man with alcoholic liver disease. He developed hypoxemia and non-cardiogenic pulmonary edema after red blood cell transfusion. Given an oxygen support, he recovered after 4 days.