迟发性输血相关性急性肺损伤

输血相关性急性肺损伤(transfusion-related acute lung injury,接受输血的危重患者发生迟发性TRALI,病死率高达40%.本文对迟发性TRALI从诊断、治疗及预防几个方面做简单的讨论,该综合征的临床判断及实验室检查水平仍有待提高.TRALI)是一种与输入含血浆血制品相关的可危及生命的临床综合征,虽然很多资料认为TRALI通常发生在输血后6小时内,但一些来自危重患者的资料显示存在一种称为迟发性TRALI的情况,即发生在输血6小时后的TRALI.迟发性TRALI综合征常发生在输血后6～72小时,多达25%的     

Recurrent transfusion-related acute lung injury

BACKGROUND: Transfusion-related acute lung injury (TRALI) is a rare condition that is commonly associated with the transfusion of donor plasma containing WBC antibodies. Biologically active lipids that accumulate during storage of RBCs and platelets may also cause TRALI. There has been only one previously reported case of recurrent TRALI. CASE REPORT: A patient received a transfusion 2 days after undergoing hysterectomy; she developed TRALI after receiving the transfusion. The patient recovered after being on ventilation for 6 days but received an additional transfusion and had a second episode of TRALI, which required further ventilation. RESULTS: Laboratory investigation of the first episode of TRALI suggested the presence of HLA-A2 (N = 1) and granulocyte-specific IgM antibodies (N = 2) in the sera from three of the donors. All three sera reacted in crossmatch studies with the patient's granulocytes and lymphocytes. Lymphocyte-specific IgG antibodies were detected in the patient's serum. There was no evidence to suggest the involvement of WBC antibodies in the second episode of TRALI. Antibody screening of the donors' samples and both forward and reverse crossmatch studies were negative. CONCLUSION: The first episode of TRALI seems to be due to the action of HLA-A2 and granulocyte-specific IgM antibodies. The second episode may have been due to the action of lipid neutrophil-priming agents in the donors' units in association with the patient's underlying pulmonary condition (i.e., recovering from lung injury). TRALI can recur if a patient requires further transfusion support shortly after an initial episode of TRALI.     

Reducing transfusion-related acute lung injury risk: evidence for and approaches to transfusion-related acute lung injury mitigation

Transfusion-related acute lung injury (TRALI) is a major cause of transfusion-related morbidity and mortality. Although the pathogenesis of TRALI is incompletely understood, substantial data from hemovigilance systems, large case series, clinical trials, and animal models have identified antileukocyte antibodies as a major precipitant and have contributed to the development of concrete interventions to reduce the risk of TRALI. This review presents the clinical data supporting specific donor management strategies to reduce TRALI risk and their observed clinical efficacy. Novel strategies that use the donor health questionnaire combined with testing are discussed, and important challenges that remain going forward are explored.     

Experimental models of transfusion-related acute lung injury

Transfusion-related acute lung injury (TRALI) is defined clinically as acute lung injury occurring within six hours of the transfusion of any blood product. It is the leading cause of transfusion-related death in the United States, but under-recognition and diagnostic uncertainty have limited clinical research to smaller case control studies. In this review we discuss the contribution of experimental models to the understanding of TRALI pathophysiology and potential therapeutic approaches. Experimental models suggest that TRALI occurs when a host, with a primed immune system, is exposed to an activating agent such as anti-leukocyte antibody or a biologic response modifier such as lysophosphatidylcholines. Recent work has suggested a critical role for platelets in antibody-based experimental models and identified potential therapeutic strategies for TRALI.     

Diagnostic and pathogenetic considerations in transfusion-related acute lung injury

Transfusion-related acute lung injury (TRALI) is an infrequent but life- threatening complication of hemotherapy. The findings in 36 cases are described. The typical clinical presentation includes acute respiratory distress characterized by hypoxemia and fulminant pulmonary edema. The onset is usually within 4 hours of transfusion and is accompanied by hypotension. In most patients (81%), recovery is rapid and complete. In 89 percent of cases, granulocyte or lymphocytotoxic antibodies are found in the serum of the implicated blood product which contained plasma. HLA-specific antibodies were identified in donor serums in 65 percent of cases evaluated. The passive transfer of these antibodies may promote complement activation and subsequent pulmonary injury. TRALI is an important cause of transfusion-associated morbidity and is probably often misdiagnosed. Blood banks need to identify donors whose plasma causes these reactions in order to prevent their recurrence.     

HLA class II antibodies in transfusion-related acute lung injury

BACKGROUND: Transfusion-related acute lung injury (TRALI) is a serious, sometimes fatal, complication of transfusion. Granulocyte and HLA class I antibodies present in blood donors have been associated with TRALI. HLA class II antibodies have recently been described in a few cases of TRALI. STUDY DESIGN AND METHODS: Donors involved in TRALI reactions reported to a blood center over an 18-month period were tested for HLA class I and II antibodies as well as granulocyte antibodies, if HLA antibodies were not identified. RESULTS: HLA class II antibodies were identified, in at least one donor, in 7 (64%) of 11 cases of TRALI. HLA class I antibodies were identified in combination with HLA class II antibodies in 5 of these 7 cases. HLA class I antibodies were exclusively identified in 2 cases. Granulocyte antibodies were identified in 1 case, and no antibodies were identified in another. CONCLUSION: In addition to HLA class I antibodies, HLA class II antibodies are associated with TRALI. Testing of donors for HLA class II antibodies as well as HLA class I and granulocyte antibodies is recommended as part of the investigation of suspected cases of TRALI.     

Possible involvement of heparin-binding protein in transfusion-related acute lung injury

BACKGROUND: In antibody-mediated nonhemolytic transfusion reactions, transfusion-related acute lung injury (TRALI) tends to occur typically within 2 hours after a blood transfusion. White cell antibodies or immune complexes have been frequently shown to be associated with the syndrome, although the mechanisms by which they induce TRALI are poorly understood. The aim of this study was to characterize soluble mediators that are released from cells at an early stage after immune stimulation. STUDY DESIGN AND METHODS: To explore the mechanism of TRALI, an in vitro whole-blood cell culture assay was established in which cells were stimulated by human antibodies and the activation of neutrophils was monitored by a cell surface marker (Mac-1) with flow cytometry and by measurement of the release of soluble factors, including perforin, interleukin-6, tumor necrosis factor-alpha, and heparin-binding protein (HBP) with enzyme-linked immunosorbent assays. In addition, the involvement of two neutrophil FcgammaRs (FcgammaRIIIb and FcgammaRIIa, also known as CD16 and CD32, respectively) was examined during antibody-induced cell activation with anti-FcgammaR blocking antibodies. RESULTS: Substantial amounts of HBP were released within 30 minutes of stimulation by human antibodies, although other soluble mediators were not released within the same period. Furthermore, the release of HBP was mediated via signals through both FcgammaRIIIb and FcgammaRIIa. CONCLUSION: HBP appears to be one of the primary effector molecules of antibody-mediated nonhemolytic transfusion reactions including TRALI.     

Platelets induce neutrophil extracellular traps in transfusion-related acute lung injury

There is emerging evidence that platelets are major contributors to inflammatory processes through intimate associations with innate immune cells. Here, we report that activated platelets induce the formation of neutrophil extracellular traps (NETs) in transfusion-related acute lung injury (TRALI), which is the leading cause of death after transfusion therapy. NETs are composed of decondensed chromatin decorated with granular proteins that function to trap extracellular pathogens; their formation requires the activation of neutrophils and release of their DNA in a process that may or may not result in neutrophil death. In a mouse model of TRALI that is neutrophil and platelet dependent, NETs appeared in the lung microvasculature and NET components increased in the plasma. We detected NETs in the lungs and plasma of human TRALI and in the plasma of patients with acute lung injury. In the experimental TRALI model, targeting platelet activation with either aspirin or a glycoprotein IIb/IIIa inhibitor decreased NET formation and lung injury. We then directly targeted NET components with a histone blocking antibody and DNase1, both of which protected mice from TRALI. These data suggest that NETs contribute to lung endothelial injury and that targeting NET formation may be a promising new direction for the treatment of acute lung injury.     

Recurrent transfusion-related acute lung injury after a two-year interval

Transfusion-related acute lung injury (TRALI) is a life-threatening complication of blood transfusion. The epidemiology and pathogenesis of TRALI are not well established. A Medline literature search shows only rare reports of recurrent TRALI, all occurring soon after the first episodes. We report a case of recurrent TRALI after a 2-year interval. A patient developed TRALI after transfusion of 4 units of fresh frozen plasma for gastrointestinal bleeding due to oesophageal varices in September 2002. The patient required mechanical ventilation but recovered completely. Two years later, in October 2004, the patient experienced a second episode of TRALI during liver transplantation for hepatitis C virus /alcoholic cirrhosis. Again, the patient recovered after ventilator support. Laboratory investigation of the first TRALI episode (2002) showed antibodies against class II human leukocyte antigens (HLA) in three female donors. Laboratory investigation of the second episode (2004) showed anti-DR52 (HLA class II) antibodies in one female donor matching the DR-52 HLA class II antigen in the recipient. TRALI can rarely recur. Consideration of future blood needs for patients experiencing recurrent TRALI should include preventive measures against further TRALI reactions, such as blood from male donors or blood less than 14 days old.     

Storage time of blood products and transfusion-related acute lung injury

BACKGROUND: Besides white blood cell antibodies in plasma‐rich products, another cause of transfusion‐related acute lung injury (TRALI) could be release of biologically active substances during storage of cellular blood products. We aimed to investigate the association of storage time and risk of TRALI for different product types. STUDY DESIGN AND METHODS: We compared storage time of blood products transfused within 6 hours before the onset of TRALI to storage time of a representative sample of all blood products transfused in the Netherlands. Generalized linear models were used to correct for confounding variables. RESULTS: Platelets (PLTs) in plasma transfused to TRALI patients were stored for 0.7 (95% confidence interval [CI], 0.073 to 1.3) days longer than those transfused to controls. The relative risk of TRALI, after receiving PLTs stored for 4 or 5 days, compared to 3 days or less, was 5.8 (95% CI, 0.99 to 110) and increased to 6.3 (95% CI, 1.1 to 118) after more than 5 days (i.e., 6 or 7 days). CONCLUSIONS: While longer storage of buffy coat–derived PLTs was associated with an increased risk of TRALI, storage of plasma for up to 2 years and red blood cells for up to 35 days was not associated with the risk of TRALI.     

输血相关急性肺损伤大鼠模型建立及肺组织病理研究

目的 建立输注人类血浆大鼠输血相关急性肺损伤(TRALI)模型并分析其肺组织病理特点.方法 将分离存储21 d后人AB型全血中的血浆,经静脉输注给经脂多糖预处理后的雄性Sprague Dawley大鼠,建立TRALI 模型;分析大鼠肺组织病理及湿干比变化.结果 输注了从存储后人全血中分离血浆的大鼠成功建立起TRALI模型,大鼠肺组织出现肺泡间隔增厚、肺泡内纤维蛋白浸润、肺泡内出血、支气管壁增厚等病理变化,肺组织湿干比增高等改变.结论 所建立的输注(人)存储后全血中分离的血浆的TRALI大鼠模型具有可行性、实用性与稳定性等特点,为诊断和治疗TRALI提供了实验基础.