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.     

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.     

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.     

输血相关性急性肺损伤2例并文献复习

目的 探讨输血相关性急性肺损伤(TRALI)的临床表现、治疗及预后.方法 报道2例致死性TRALI的临床资料和治疗经过.并复习相关文献.结果 2例患者在输血后出现明显的呼吸困难、低氧血症、低血压等非心源性肺水肿表现,病情发展迅速,均抢救无效死亡.结论 TRALI死亡率高,危害性大,临床应提高对其的防范意识.     

中和IL-17A对输血相关急性肺损伤小鼠的保护作用

目的观察IL-17A在输血相关急性肺损伤小鼠中的表达,探讨中和IL-17A对输血相关急性肺损伤小鼠的影响。方法采用"二次打击"(LPS+MHC-Ⅰm Ab)模型,8~10周BALB/C雄性小鼠32只,应用随机数据表完全随机分成4组:正常(normal)组、LPS+MHC-Ⅰm Ab组、LPS+isotype组、LPS+PBS组,每组8只。腹腔注射LPS 0.1 mg/kg,24 h后尾静脉分别给予MHC-Ⅰm Ab(1 mg/kg)或等体积的isotype和PBS,2 h后检测肺泡灌洗液和外周血中IL-17的表达。另选取32只BALB/C雄性小鼠,观察anti-IL-17A抗体预处理对肺损伤的影响,随机分为4组:normal组、LPS+MHC-Ⅰm Ab+anti-IL-17A组、LPS+MHC-Ⅰm Ab+isotype组、LPS+MHC-Ⅰm Ab+PBS组,提前1 h尾静脉注射anti-IL-17A(50μg/只)、isotype(50μg/只)或等体积的PBS,二次打击造模后2 h取材,测定肺泡灌洗液中蛋白浓度和肺干湿重比,检测肺泡灌洗液和外周血中细胞因子水平,计数肺脏中性粒细胞,评估各组小鼠肺损伤和炎症反应程度。数据采用Prism5.0(Graph Pad Software,USA)软件包进行统计学处理。结果与其他三种相比,二次打击模型(LPS+MHC-Ⅰm Ab)组小鼠肺泡灌洗液和外周血中IL-17A表达显著升高,且肺组织中性粒细胞数明显增多。anti-IL-17A预处理后,肺组织中性粒细胞浸润减少,肺干湿重比减小,肺泡灌洗液蛋白含量降低,外周血促炎因子水平显著下调。结论 IL-17A在输血相关急性肺损伤中显著升高,anti-IL-17A预处理后显著改善输血相关急性肺损伤小鼠炎症反应和肺组织损伤。     

Transfusion-related acute lung injury caused by two donors with anti-human leucocyte antigen class II antibodies: a look-back investigation

Transfusion-related acute lung injury (TRALI) is considered as one of the most important complications of blood transfusion. Previous look-back investigations have revealed unrecognized cases. We report two cases of TRALI in brief and the outcomes of transfusion in the recipients of previous components from the implicated donors. This look-back investigation was a retrospective case-note study assessing whether there were any untoward events associated with the previous transfusions. 18 patients were identified as having received a blood component transfusion from one of the two donors with anti-human leucocyte antigen (HLA) antibodies to antigens occurring frequently in the local population. One of the five patients receiving a unit of fresh frozen plasma had an evidence of TRALI, which was not diagnosed at the time. A second patient, who had been HLA typed and who carried a full match of antigens for the antibody specificities of the plasma received, had no evidence of a reaction. There were no documented reactions in 13 recipients of red cells in optimal additive (OA) solution. Cases of TRALI may go unrecognized. Not all patients with antibody/antigen concordance will develop clinical signs. Red cells in OA solution from donors with anti-HLA antibodies appear to have a low risk of causing clinically evident lung damage.     

急性胰腺炎并发急性肺损伤的影响因素及临床意义

目的　探讨急性胰腺炎患者并发急性肺损伤的影响因素及临床意义。方法　对 2 5 0例急性胰腺炎患者进行回顾性分析 ,观察不同临床分型、病程不同时期和有无全身炎症反应综合征 (SIRS)及持续时间对肺损伤发生率的影响。同时分析急性胰腺炎并发急性肺损伤时与病情严重程度如急性生理学与慢性健康状况 (APACHE )评分、急性呼吸窘迫综合征 (ARDS)和多器官功能障碍综合征 (MODS)发生率以及预后的关系。结果　急性胰腺炎的不同临床分型、病程不同时期急性肺损伤的发生率有显著差异 (P均 <0 .0 1) ;SIRS组的急性肺损伤的发生率和非 SIRS组有显著差异 (P<0 .0 1) ;SIRS持续时间越长 ,急性肺损伤的发生率越高。并发急性肺损伤组患者 APACHE 评分以及 ARDS和 MODS的发生率明显增加 ,两组间有显著差异 (P均 <0 .0 1)。急性肺损伤组治愈率下降、病死率增加 ,两组间有显著差异 (P<0 .0 5 )。结论　 SIRS是引起并发急性肺损伤的重要因素 ,急性肺损伤对急性胰腺炎患者病情和预后有重要影响。     

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.     

输血相关急性肺损伤及其预防与控制策略的研究进展

输血相关急性肺损伤(TRALI)是指输血后6h内发生的急性肺损伤(ALI),是输血导致患者死亡的主要原因之一.目前对TRALI发病机制的假说包括“二次打击”学说与“阈值模型”学说等.超过80％ TRALI是由输注的血液制品中含特异性抗人类白细胞抗原(HLA)或人类中性粒细胞抗原(HNA)抗体介导的,并且导致TRALI发生的血液制品,主要来源于有多次妊娠史的女性献血者.目前,多个国家实行以男性献血者为主体,供应高血浆含量血液制品的临床预防、控制TRALI策略,以效降低TRALI发生率.笔者拟就TRALI的定义、发病机制、诊断、预防控制策略进行综述.     

半相合造血干细胞移植中发生的输血相关急性肺损伤:1例病例报告附文献复习

目的探讨HLA半相合造血干细胞移植过程中发生输血相关急性肺损伤(TRALI)的风险性及其处理、预防措施。方法对1名行HLA半相合造血干细胞移植治疗的患者在移植过程中出现的TRALI的临床发病特点、实验室检查、影像检查、治疗措施进行分析,并对相关文献做复习。结果发现该患者在移植过程中因输注机采新鲜血小板而导致TRALI,经积极抢救无效,最终病情恶化死亡。结论半相合造血干细胞移植过程中若反复输血(包括血液成分),存在发生TRALI的较大风险,积极有效的预防和及时的处理措施显得尤为必要。     

单侧肺滴入酸后急性肺损伤的研究

目的：观察酸滴入侧的急性肺损伤（ＡＬＩ）的形成及对测肺有无损伤形成。方法：１８只新西兰兔随机分为生理盐水（ＮＳ）滴入对照组和盐酸入损伤组。以向右肺内滴入ＮＳ或ＨＣｌ后的血气、气道压力、动静态顺应性、肺湿／干比（Ｗ／Ｄ）和支气管肺泡灌洗液（ＢＡＬＦ）中总蛋白（ＴＰ）、总磷脂（ＴＰＬ）、饱和磷脂占总磷脂比（ＤＳＰＣ／ＴＰＬ）及肺组织形态学来判断有无ＡＬＩ及其严重程度。结果：损伤组在酸滴入后ＰａＯ２较基     

脓毒症急性肺损伤大鼠肺组织细胞凋亡的研究

目的观察脓毒症急性肺损伤（ALI）大鼠肺组织的细胞凋亡情况。方法24只SPF级SD大鼠采用盲肠结扎穿孔术（CLP）复制脓毒症模型,分别于CLP后0、12、36和72h颈椎脱臼法处死大鼠,取肺组织。行肺组织HE染色,观察病理变化,以透射电镜、TUNEL法检测细胞凋亡。结果HE染色可见,CLP后12、36、72h肺泡间隔增宽,间质充血水肿,肺泡腔变窄,炎症细胞渗出。TUNEL法检测发现,CLP后12、36、72h肺组织内细胞凋亡指数（Al）增加,其中36hAl值最高（P〈0．01）。透射电镜证实细胞凋亡的特征性改变。结论脓毒症大鼠肺组织的Al明显增加,细胞凋亡可能在脓毒症ALI发生、发展中起着重要作用。     

急性肺损伤环氧合酶2表达的研究

目的：探讨急性肺损伤（ＡＬＩ）肺组织环氧合酶 ２（ＣＯＸ ２）ｍ ＲＮＡ 表达和ＡＬＩ中前列腺素（ＰＧｓ）变化的关系,以及ＣＯＸ ２ 在ＡＬＩ发病中的可能作用。方法：在脂多糖（ＬＰＳ）诱发的ＡＬＩ模型,采用逆转录聚合酶链反应,检测肺组织ＣＯＸ ２ ｍ ＲＮＡ表达情况,并观察了ＰＧｓ的变化。结果：生理盐水对照组的大鼠肺组织有极少量的ＣＯＸ ２ ｍ ＲＮＡ表达（０．３２±０．１１）;而在ＡＬＩ大鼠,肺组织ＣＯＸ ２ｍ ＲＮＡ表达显著增加,比生理盐水对照组升高达５～８ 倍,同时伴有ＰＧｓ的升高〔生理盐水对照组为（１４１．６４±４１．７９）μｇ·Ｌ－ １ ·ｇ－ １ ,ＡＬＩ大鼠分别为（１９０．５３±４７．９１）～（４７０．９５±１８４．１７）μｇ·Ｌ－ １·ｇ－ １ 〕。结论：正常肺组织有极少量的ＣＯＸ ２ ｍ ＲＮＡ表达,ＣＯＸ ２参与ＡＬＩ的发病,并可能是引起ＡＬＩ时ＰＧｓ升高的主要同工酶。     

甘遂辅助治疗重症急性胰腺炎并发急性肺损伤的临床研究

目的观察中药甘遂对于重症急性胰腺炎(SAP)并发急性肺损伤(ALI)的疗效。方法将35例SAP并发ALI患者随机分为2组,对照组予以常规治疗方案,治疗组在对照组基础上加用甘遂治疗。对比2组肺功能指数、血气分析指数以及肿瘤坏死因子-α(TNF-α)的水平变化。结果治疗第5天时,治疗组的血清TNF-α浓度明显低于对照组(P<0.01)。治疗组PaO2/FiO2、PaO2及RR指标明显优于对照组(P<0.01或P<0.05)。治疗组住院时间、ICU治疗时间明显短于对照组,ARDS发生率亦明显低于对照组(P<0.01)。结论甘遂可以有效控制或缓解SAP患者ALI的进展。     

外源性肺表面活性物质治疗脓毒性急性肺损伤的机制研究

目的;观察外源性肺表面活性物质早期治疗对脓毒性急性肺损伤的疗铲及对内源性ＰＳ的影响。方法：实验动物在机械通气下建立脓毒性ＡＬＩ模型,早期气管内稍许主有机提取的ＰＳ１００ｍｇ／ｋｇ,连续治疗６小时,观察氧合指数,肺内分流,肺动脉顺应性的变化;并对支气管肺泡灌洗液磷脂含量和表面张力进行分析。用Ｗｅｓｔｅｒｎ ｄｏｔ ｂｌｏｔ法测定ＰＳ特异性结合蛋白含量,用Ｎｏｒｔｈｅｒｎ ｂｌｏｔ法测定ＳＰ－ＡｍＲＮ     

髓系细胞触发受体2在急性肺损伤小鼠肺泡巨噬细胞上的表达

目的：研究髓细胞触发受体2（TREM2）在脂多糖（LPS）致急性肺损伤（ALI）小鼠肺泡巨噬细胞（AM）上的表达,并探讨其作用机制及意义。方法：采用动物实验,以腹腔注射大剂量LPS诱导ALI模型;以腹腔注射生理盐水作为对照。用荧光定量逆转录-聚合酶链反应（RT—PCR）对AM表达的TREM2mRNA做定量分析。用ELISA对支气管肺泡灌洗液中的肺肿瘤坏死因子（TNF—α）定量检测。结果：AM在正常情况下表达大量的TREM2,在LPS造成急性损伤后表达大幅度下降。TREM2与TNF—α的表达呈负相关（P〈0．001）。结论：TREM2可能在LPS致ALI中起重要的抗炎作用。     

静脉注射内毒素致大鼠急性肺损伤模型的病理生理学指标评价

目的 观察静脉注射内毒素所致大鼠急性肺损伤（ALI）模型的病理生理学指标，全面评价该模型。方法 将33只Wistar大鼠随机分为实验组和对照组，对照组于静脉注射生理盐水后2h处死动物，实验组静脉注射革兰阴性菌脂多糖后分别于2、4和6h后处死，比较各组死亡率、呼吸频率、肺脏病理、血气指标、肺顺应性、右肺湿重／体重比值、血清和支气管肺泡灌洗液（BALF）中肿瘤坏死因子-α（TNF-α）水平。结果实验组6h动脉血氧分压（PaO）跌至69．18mmHg（1mmHg=0．133kPa）；肉眼肺脏可见明显淤血、出血点和水肿；光镜下肺泡正常结构消失，间质水肿增宽，大量炎性细胞浸润，毛细血管明显扩张、充血，白细胞附壁；肺顺应性跌至正常值的47％，右肺湿重／体重比值相当于正常值的137％；血清、BALF中TNF-α水平急剧升高。结论以肺部特征性病理改变和PaO2下降大于30％（与基线值相比）作为判定大鼠ALI模型是否成功的主要指标；以肺顺应性、湿重／体重比值作为辅助指标，可能更适合于大鼠ALI模型。     

Activation of polymorphonuclear neutrophils by immune complex: possible involvement in development of transfusion-related acute lung injury

Transfusion-related acute lung injury (TRALI) is a serious side-effect of transfusion. We presumed that immune complex (IC)-activated polymorphonuclear neutrophils (PMNs) are involved in the development of TRALI. The aim of this study is to examine the various effects of ICs on normal human PMNs. ICs used here were artificially formed by combining soluble human leucocyte antigen (HLA) class II-positive serum and anti-HLA class II antiserum. The abilities of ICs to trigger PMNs and induce the production of soluble mediators and the involvement of the Fc receptor (FcR) in the activation of PMNs by ICs were investigated. Moreover, the ability of the culture supernatant of PMNs incubated with ICs regarded to induce the apoptosis of lung microvascular endothelial (LME) cells was examined. The results proved that PMNs are triggered by ICs resulting in the acceleration of the production of tumour necrosis factor-alpha (TNF-alpha), perforin and Fas ligand, in which FcR on PMNs appears to be involved. Furthermore, the culture supernatants of PMNs cultured with ICs were revealed to induce the apoptosis of LME cells. In conclusion, the ICs used here were proved to induce PMNs to release cytotoxic factors upon activation. These results suggest that ICs are mediators of the development of TRALI.