细胞因子及C-反应蛋白与输血相关急性肺损伤的研究进展

输血相关急性肺损伤(TRALI)是指输注血液制品6 h内发生的急性呼吸窘迫综合征,是输血导致死亡的主要原因之一,且尚未有完善的特异性治疗及预防方案。到目前为止,TRALI的发病机制尚未完全清楚,普遍认为与"二次打击学说"及"阈值学说"有关。研究者们证实细胞因子及C-反应蛋白(CRP)与TRALI的发病机制有关,本文旨在概括几种细胞因子及CRP在TRALI发生发展机制中的作用,为国内临床研究者们在TRALI诊断、治疗和预防方面提供新的策略。     

输血相关急性肺损伤的发病机制及预防策略

输血相关急性肺损伤(TRALI)是指输入血制品6 h内发生的急性肺损伤,是输血导致患者死亡的主要原因之一。TRALI的发病机制有抗体介导和非抗体介导两种,同时较为认可的"二次打击学说"和阈值模型也得到许多动物模型试验的支持。在TRALI的发病机制中中性粒细胞的激活扮演着重要作用。因此,临床制定严格的输血策略是预防TRALI的最有效方法,供血机构排除高风险献血者(如有多次妊娠史的女性献血者)也会有效降低TRALI的发生发展。同时,临床和供血机构仍在探讨"量身输血"、血浆汇集等策略对降低TRALI发生的可行性。     

输血相关急性肺损伤研究进展

输血相关急性肺损伤(transfusion related acute lung injury,TRALI)系指输入血液、血浆及相关制品6h内急性发作的临床综合症[1],主要表现为肺部受损的症状,是一种严重的非传染性的输血并发症,发作快,预后不佳,致死率可达6％～10％[2-4].TRALI目前已成为输血医学界关注和研究的焦点,但仍有诸多机制尚不明确.笔者从其发病机制、临床表现及诊断、治疗及预防等方面综述如下. 1发病机制 1.1抗原抗体学说抗原抗体学说的主要观点认为,献血者血液中存在有抗受体细胞的抗体,而受体血液中也可存在抗供体细胞的抗体,输血后双方抗原抗体相结合后发生一系列的反应从而导致肺损伤[3].临床上最常见的主要是供者血液成分中含有抗对受血者白细胞抗原的抗体,而受血者的白细胞抗体与供血者的白细胞抗原发生反应则较少见.抗原抗体发生反应后,抗体可直接黏附并损伤受血者肺部内皮细胞或肺泡上皮细胞,从而增加肺毛细血管的通透性,最终导致肺水肿的发生;此外,Nishimura等[5]证实抗原抗体反应还能激活补体,产生的补体片段可促使肺部毛细血管渗漏,迅速加重急性肺损伤.但并不是所有的TRALI患者都表现为抗原抗体阳性,说明TRALI还存在其他的发病机制.     

输血相关性急性肺损伤

输血相关性急性肺损伤（TRALI）是指输入血液或血液制品后数小时内出现的以急性非心源性肺水肿和低氧血症为主要表现的临床综合征。起病急，病情重，死亡率高，是住院患者输血过程中的常见严重并发症。确切的发病机制尚未完全明了，抗体介导的肺损伤、“二次打击”学说是其可能的发病机制。提高对TRALI的认识，对引起TRALI的供体血液进行识别分离，对经产妇或者含有HLA抗体的血液成分进行筛选，以及去白细胞处理，可有效防止TRALI的发生。     

输血相关急性肺损伤的研究进展

输血相关急性肺损伤(TRALI)是一种可以致命的输血并发症,主要表现为在输血后6 h内出现急性呼吸困难、双肺水肿、低血压、发热和低氧血症等。多种血液制品均可诱发TRALI,包括全血、红细胞、血小板、新鲜冷冻血浆、粒细胞、冷沉淀及免疫球蛋白(IVIG)。但是目前还没有关于输注清蛋白可以导致TRALI的报道。输注总量与TRALI发生的关系不明显,极少量(10 mL)血液制品即可引发TRALI。     

儿童手术患者输血相关急性肺损伤调查

目的调查输血相关性急性肺损伤(TRALI)在儿童手术输血患者发病情况。方法对2007年1月～2010年12月期间住院的2 495名手术输血儿童调查,分析发生呼吸窘迫或者肺水肿的患者输血情况,结合临床症状和发病时间判断是否为TRALI。同时分析发生TRALI的临床发病特点、实验室检查、影像检查、治疗措施、预后。结果 2 495名儿童3 423次输血,其中35名患者输血后发生出现呼吸系统疾病,2名符合TRALI的临床表现,这2名患者输注的血液制品为女性献血者新鲜冰冻血浆。结论儿童手术输血患者发生TRALI的率为0.58‰,富含血浆的血液制品是引起儿童手术患者发生TRALI的危险因素。     

输血相关急性肺损伤的发生率和预防策略

输血相关急性肺损伤(TRALI)是输血相关死亡的首要原因,也是输血相关发病的最常见原因之一。在某些患者人群中有较高的TRALI发生率和死亡率。目前尚无治疗TRALI的特效方法,主要通过预防达到降低TRALI发病;已有多个国家实施排除女性献血者血浆、或有妊娠史的女性献血者血浆、或白细胞抗体筛查有反应性的有妊娠史女性献血者血浆的策略,有效降低了免疫性TRALI发生率。排除所有女性献血者捐献机采血小板似乎不可行,会导致献血者大量损失,影响临床供应。用献血者健康问卷调查识别具有任何妊娠史的同种免疫的高风险献血者,筛查这些献血者的抗-HLA-A2、抗-HLA-Ⅱ类和抗-HNA-3a等白细胞抗体,排除具有这些抗体的献血者献血,可能是1种即经济又有效的TRALI缓解策略。     

经溶剂和去污剂处理过的血浆（S／D血浆）中检测不出白细胞活性抗体

背景输血相关急性肺损伤(TRALI)是一种能危及到生命的并发症,虽然各种血液制品都与TRALI有关联,但其中新鲜冰冻血浆(FFP)是最常被提到。由于献血者血浆中的白细胞活性抗体常与此病症同时出现,因此假定TRALI的发生是由免疫介导的。相对于源于单个献血者的FFP,溶剂/去污剂(S/D)血     

非抗体介导的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,TRALI)是输血导致死亡的首要原因,但临床缺乏有效的防治手段,了解其病理生理机制有助于更有效地预防TRALI。根据介导因子不同,可将其分为抗体介导(免疫性)和非抗体介导(非免疫性)TRALI;前者主要由被动输注内源性抗体导致,后者主要由血制品中的可溶性分子和某些细胞成分介导。本文旨在对非抗体介导TRALI的发病机制及研究现状进行综述,为临床工作提供理论指导。     

输血相关性急性肺损伤回顾性调查分析——附2例报告

目的通过对2例输血相关性肺损伤(transfusion-related actute lung injury,TRALI)的调查并分析其发病因素,为TRALI的预防提供参考。方法回顾性调查2名抢救性患者在输血治疗过程中发生TRALI反应的临床病历和献血者的相关资料,分析发生TRALI的危险因素。结果 2名创伤性手术患者均在输血治疗过程中输入了富含血浆的血液成分而导致TRALI发生,虽经积极抢救,1例治愈,1例死亡。2名TRALI患者所输血液成分来自4名供血者,其中2人为经产妇,另2人均为男性献血者,追踪4名供血者以往的受血者,无1人发生TRALI反应。结论患者输血治疗时有大的创伤性因素存在,是发生TRALI的危险因素;富含血浆是引起发生TRALI的直接诱因,存在TRALI高危因素的患者应尽量减少血浆制品的输入以预防TRALI的发生。     

Transfusion-related acute lung injury

Transfusion-related acute lung injury (TRALI) is characterized by the sudden development of noncardlogenic pulmonary edema (acute lung Injury) after transfusion of blood products. Poor awareness of TRALI outside of the blood transfusion medicine community has led to a serious underestimation of this condition, currently the most Important severe complication of blood transfusion. Concern for the transfer of donor antileukocyte antibodies has prompted major changes in the management of the blood supply in some countries; however, recent studies have suggested alternative pathophyslological mechanisms for TRALI related to the shelf life of cellular blood products. Although all blood products have been implicated, most reported cases were associated with fresh frozen plasma, red blood cell, and platelet transfusions. Because many patients have additional predisposing factors for acute lung injury, carefully designed prospective studies are needed to fully assess attributable risk related to transfusion. The treatment of TRALI is supportive, and the prognosis is generally better than for other causes of acute lung Injury. As many as one third of all patients who develop acute lung injury have been exposed to blood products. TRALI may be an important and potentially preventable cause of acute lung injury.     

The relation between aged blood products and onset of transfusion-related acute lung injury. A review of pre-clinical data

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion related morbidity and mortality. TRALI is suggested to be a "two hit" event. The "first hit" is the underlying condition of the patient which results in sequestration and priming of neutrophils in the pulmonary compartment. The "second hit" is the transfusion of either human leukocyte antibodies or aged blood products which results in activation of the primed neutrophils and finally in pulmonary edema. The present review focuses on pre-clinical studies investigating the role of blood products containing aged cells (red blood cells, RBCs, and platelet concentrates, PLTs) and the onset of TRALI. Several mechanisms are under scrutiny. The first suggested mechanism is that soluble mediators accumulating during storage of RBCs and PLTs may play a role, including bio-active lipids or soluble CD40L. These soluble factors were found to cause lung injury in the presence of a "first hit". Another proposed mechanism involves the aged erythrocyte itself. During storage, the erythrocyte undergoes numerous changes in its biochemical and structural condition and acquires pro-inflammatory properties, sometimes collectively referred to as the "red cell storage lesion". Although it could be speculated that all of these factors may be involved in the onset of TRALI, only one pre-clinical study shows an association between the aged erythrocyte and the onset of TRALI. The suggested mechanism is a decrease in the chemokine scavenging function of the erythrocyte by reduction of the Duffy antigen expression resulting in an increase in lung injury. Further research is needed to elucidate possible mechanisms of onset of TRALI by aged blood products.     

Transfusion-related acute lung injury

Transfusion-related acute lung injury (TRALI) refers to a clinical syndrome of acute lung injury that occurs in a temporal relationship with the transfusion of blood products. Because of the difficulty in making its diagnosis, TRALI is often underreported. Three not necessarily mutually exclusive hypotheses have been described to explain its etiogenesis: antibody mediated, non-antibody mediated, and two hit mechanisms. Treatment is primarily supportive and includes supplemental oxygen. Diuretics are generally not indicated, as hypovolemia should be avoided. Compared with many other forms of acute lung injury, including the acute respiratory distress syndrome, TRALI is generally transient, reverses spontaneously, and carries a better prognosis. A variety of prevention strategies have been proposed, ranging from restrictive transfusion strategies to using plasma derived only from males.     

TRALI : aspects physiopathologiques

Transfusion-related acute lung injury (TRALI) is defined clinically as a pulmonary edema occurring within 6 hours after transfusion of blood products. This is a major cause of morbidity and mortality associated with blood transfusion. Its pathophysiology is complex and not fully understood. TRALI is the result of a neutrophil-mediated damage to the pulmonary endothelium. Possible causal agents include alloantibodies against leucocytes and biologically active mediators accumulated in stored blood products. Leucostasis in the recipient??s lung is a predisposing state due to leucocyte priming preceding the activation of neutrophils by blood transfusion leading to lung injury. TRALI is frequent in critical ill patients as they meet several risk factors associated with this injury. This review focuses on the pathogenesis of TRALI based on epidemiologic and experimental published data.     

Complications non infectieuses et non immunologiques des transfusions érythrocytaires

Red blood cells transfusion can cause both hemodynamic pulmonary edema and acute lung injury. Transfusion related acute lung injury (TRALI) is frequently unrecognized. TRALI is due to recipient’s leukocytes activation induced by antibody directed against leukocytes or by reactive lipid products generated during blood storage. Massive transfusions are associated with specific risks: hypothermia, citrate toxicity, dyskalemia, dilutional coagulopathy. Per or postoperative autotransfusion of retrieved blood raises the question of the possible contamination of the transfused blood with cells or bioactive products.     

Transfusion reactions: newer concepts on the pathophysiology, incidence, treatment, and prevention of transfusion-related acute lung injury

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality. TRALI presents as acute lung injury (ALI) within 6 hours after blood product transfusion. Diagnosing TRALI requires a high index of suspicion, and the exclusion of circulatory overload or other causes of ALI. The pathophysiology of TRALI is incompletely understood, but in part involves transfusion of certain anti-neutrophil antibodies, anti-HLA antibodies, or other bioactive substances, into susceptible recipients. Recent studies have identified both recipient and transfusion risk factors for the development of TRALI. This article describes these TRALI risk factors, as well as diagnosis, treatment and prevention strategies.     

White blood cell-reactive antibodies are undetectable in solvent/detergent plasma

BACKGROUND: Transfusion-related acute lung injury (TRALI) is a life-threatening complication of transfusion. Although all types of blood products have been associated with TRALI, fresh-frozen plasma (FFP) is the most commonly implicated component. It has been postulated that TRALI is an immune-mediated event, because white blood cell (WBC)-reactive antibodies in the donor's plasma are frequently associated with the syndrome. In contrast to single donor-derived FFP, solvent/detergent (S/D) plasma is produced from multiple donations, leading to an at least 500-fold dilution of a single plasma unit. It was hypothesized that WBC-reactive antibodies are undetectable in S/D FFP. STUDY DESIGN AND METHODS: Twenty batches of S/D FFP (5 of each ABH group) were analyzed with well-established routine techniques to detect WBC antibodies. RESULTS: All samples tested negative for granulocyte-specific as well as HLA Class I and Class II antibodies. CONCLUSIONS: Different strategies to reduce the risk of TRALI are currently discussed. These include screening of all potentially immunized donors for WBC-reactive antibodies and exclusion of multiparous or all women from donating FFP. Here, it is demonstrated that neither granulocyte- nor lymphocyte-reactive antibodies are detectable in S/D FFP. Thus, S/D FFP may represent a potential alternative to reduce the risk of TRALI associated with the transfusion of FFP.     

Transfusion-Related Acute Lung Injury: Incidence, Pathogenesis and the Role of Multicomponent Apheresis in Its Prevention

SUMMARY: Although transfusion-related acute lung injury (TRALI) is now appreciated as the most common cause of death from transfusion, its incidence remains unknown. The most frequently cited figure is 1:5,000 plasma-containing components. Certain patient groups may be at significantly higher risk. TRALI is both underdiagnosed and un-derreported. It is misdiagnosed as transfusion-associated circulatory overload. Several mechanisms have been proposed for its pathogenesis-leukocyte antibodies and the 2-hit model. These may overlap, and both involve transfusion of leukocyte antibodies. Passive transfusion of leukocyte antibodies is strongly associated with TRALI; these are identified in 60-85% of cases. Multiparous blood donors are the most frequent source of these antibody-containing components. The antibodies are HLA class I and II and/or granulocyte-specific. In 50% of cases the antibody corresponds to an epitope in the patient. HLA class I antibodies have been shown to prime and activate neutrophils. Clinical reports and animal models link HNA-3a antibodies with severe lung injury. A number of TRALI prevention and risk mitigation strategies have been proposed. In the UK and the USA, these strategies have centered upon excluding 'high risk' (HLA/HNA antibody containing) plasma from fresh frozen plasma and platelet products. Multicomponent apheresis collection of platelets, plasma and red blood cells is a means of accomplishing this objective.     

Conversion to low transfusion-related acute lung injury (TRALI)-risk plasma significantly reduces TRALI

BACKGROUND: Transfusion‐related acute lung injury (TRALI) is an uncommon but serious transfusion reaction. Studies have shown that the transfusion of HLA and HNA antibodies in donor plasma can lead to TRALI. Female donors are more likely to have such antibodies due to alloantigen exposure during pregnancy. Many blood suppliers have now implemented various TRALI risk reduction strategies to unknown effect. A retrospective analysis of TRALI reactions in plasma recipients before and after the conversion to low‐TRALI‐risk plasma (all‐male donor plasma, male‐predominant plasma, nulliparous female plasma, and HLA antibody–tested plasma) is reported. STUDY DESIGN AND METHODS: Transfusion reaction reports at three large hospitals 16 months before and 16 months after the conversion to low‐TRALI‐risk plasma were analyzed. Respiratory reactions were categorized as TRALI, possible TRALI, or other (e.g., transfusion‐associated circulatory overload or allergic reactions). Reactions were reported as a percentage of total units transfused and rates for the two time periods were compared. Trends in reaction rates for other components were also compared. RESULTS: A total of 2156 transfusion reactions in association with 461,598 transfused blood components were reviewed. The incidence of combined TRALI or possible TRALI reactions, due to the transfusion of plasma, decreased from 0.0084% to zero (p = 0.052). The rate of TRALI or possible TRALI reactions in red blood cell and platelet recipients did not change significantly. CONCLUSION: The conversion to low‐TRALI‐risk plasma has reduced the incidence of TRALI reactions in plasma recipients.     

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.