Acute non‐hemolytic transfusion reactions and HLA class I antibody: advantages of solid phase assay compared with conventional complement‐dependent assay

To evaluate the specific reactivity of HLA Class I antibodies (HLA‐I Abs) in acute non‐hemolytic transfusion reactions (ANHTRs) using solid phase assays (SPAs) and conventional complement‐dependent lymphocyte cytotoxicity test (LCT). ANHTRs are major issues in transfusion medicine. Anti‐leukocyte antibodies have been implicated as one of the causative agents of transfusion‐related acute lung injury (TRALI) and febrile reaction. Antibodies to HLA Class I and/or Class II (HLA Abs) have been intensively studied using SPAs for TRALI, but not for febrile reaction. About 107 patients and 186 donors associated with ANHTRs were screened for HLA Abs by SPAs such as enzyme‐linked immunosorbent assay (ELISA) and the Luminex method. When HLA‐I Ab was detected, its specific reactivity was evaluated by comparing its specificity identified by the Luminex method using recombinant HLA molecules and cognate HLA antigens (Ags), as well as LCT with or without anti‐human globulin (AHG). The incidences of HLA Abs were as high as 32·7% of patients' serum samples and 16% of donors' serum samples. The incidence of HLA‐I Abs did not differ significantly between cases of febrile and allergic reactions. However, HLA‐I Abs associated with febrile reaction showed a significantly higher rate of possessing specific reactivity to cognate HLA Ags than those associated with allergic reactions. In addition, the Luminex method enabled the detection of HLA‐I Abs much earlier than AHG‐LCT in serum samples from a patient with febrile reaction and platelet transfusion refractoriness (PTR). SPAs seem more useful than AHG‐LCT for evaluating reactivity of antibodies in ANHTR cases.     

Allo-exposure status and leucocyte antibody positivity of blood donors show a similar relation with TRALI

Introduction: The fraction of transfusion‐related acute lung injury (TRALI) cases preventable by deferral of allo‐exposed donors has previously been estimated, under the assumption this indirectly estimated the contribution of leucocyte antibodies to the occurrence of TRALI. Our aim was to estimate the fraction preventable by deferral of leucocyte antibody positive donors and to investigate the validity of allo‐exposure as a marker for leucocyte antibodies. Methods: All donors involved in a series of previously published TRALI patients were tested for leucocyte antibodies. The observed number of antibody positive donors was compared to the expected number. From this comparison we estimated the contribution of leucocyte antibodies to the occurrence of TRALI and compared this to the previously reported estimate for allo‐exposed donors. Results: Sixty‐one TRALI patients were included. Of 288 involved donors 43 were expected and 67 were observed to be leucocyte antibody positive. The observed percentage of positive donors was 8·3% (95% confidence interval (CI): 5·1–11·5%) in excess of the expected. Overall 59% (95% CI: 34–85%) of TRALI cases was estimated to be preventable by the exclusion of all leucocyte antibody positive donors. For plasma‐poor products this was 16% (95% CI: ?5·0 to 36%). Conclusions: These estimates were similar to those previously published for allo‐exposed donors. This suggests allo‐exposure status can effectively be used in donor deferral strategies.     

Screening of multiparous women to avoid transfusion‐related acute lung injury: a single centre experience

summary The aim of this study was to investigate which approach for serological testing of multiparous donors might be feasible and effective to reduce the risk of transfusion‐related acute lung injury (TRALI). TRALI is a serious adverse event of blood transfusion. Antibodies to granulocytes and human leucocyte antigens (HLAs) are frequently detected in sera of implicated donors. These donors are often multiparous women. A general deferral of female plasma or screening strategies for leucocyte antibodies has been proposed to increase blood safety. A prospective study was initiated in 2003. Until 2006, serum samples from all female donors reporting three or more pregnancies (n = 229) were screened for the presence of antibodies against granulocytes and HLAs by immunofluorescence and agglutination tests as well as by a commercial HLA enzyme immunoassay. In total, 40% of all multiparous women were reactive in one of the assays. Twenty‐nine percent of the reactive sera contained antibodies to granulocytes but not to HLAs. During the observation period, three TRALI reactions occurred in our hospital, two of which would have been prevented if the screening program had been extended to all previously pregnant donors. We conclude from these data that, not unexpectedly, the number of previous pregnancies is not a reliable indicator for the likelihood of inducing TRALI. More importantly, screening strategies for antibodies that might induce TRALI should probably not be reduced to HLA antibody screening. This finding awaits further research.     

Impact of a transfusion-related acute lung injury reduction strategy on apheresis platelet collections

Background: Most blood centers in the US have implemented transfusion‐related acute lung injury (TRALI) mitigation strategies for apheresis platelet (AP) donations based on theoretical impact of donor loss. The aim of this study is to determine the actual impact of a TRALI mitigation strategy in a US blood center. Study Design and Methods: Daily collection events and resulting products were retrospectively obtained before and after implementation of a TRALI reduction strategy (HLA antibody testing female AP donors four or more pregnancies) for comparison. The retention rate of reassigned donors was determined by reviewing whole blood (WB) and/or apheresis red blood cell (AR) donations post reassignment. Data were obtained to compare donor frequency and split rate from reassigned (historical data) and new AP donors. Results: Mean daily collections (27.7 vs. 30.0) and total products (12,211 vs. 12,957) were significantly higher after implementation, but the number of products/collection event was lower (1.49 vs. 1.40). Mean collections/donor/year (4.0 vs. 1.8) and split rate (36% vs. 27%) were historically higher for reassigned (n = 45) versus new AP donors (n = 1,090). Seventy‐three of 112 donors (65%) testing positive for HLA antibodies returned for WB or AR donations, 31 of 45 (69%) active AP donors returned. Conclusions: Donor loss may not be adequate to estimate impact on AP inventory, as donation characteristics may differ between new donors and those reassigned. We show successful implementation of a TRALI mitigation strategy by increasing collection goals and AP donor recruitment efforts beyond donor loss. Retaining the majority of reassigned donors is feasible. J. Clin. Apheresis 2012. © 2012 Wiley Periodicals, Inc.     

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.     

Transfusion-related acute lung injury (TRALI) following autologous stem cell transplant for relapsed acute myeloid leukaemia: a case report and review of the literature

A fatal case of transfusion-related acute lung injury (TRALI) in a child post-autologous stem cell transplant for relapsed acute myeloid leukaemia is described. The implicated product was a single unit platelet concentrate containing anti-HLA A2 and granulocyte-specific anti-NA1 antibodies. The recipient typed as HLA A2/A2, NA1/NA1. This is the first reported case of TRALI following a transplant procedure for a haematological condition. It is also unusual in that the patient failed to make a full recovery and that two relevant leucocyte antibodies of clear specificity were identified in the donor plasma. The literature relating to the pathophysiology, clinical sequelae and management of TRALI is reviewed.     

The German Haemovigilance System–reports of serious adverse transfusion reactions between 1997 and 2007

Data of the German Haemovigilance System were collected from 1997 to 2007 and assessed on the basis of pre‐defined safety standards. Suspected cases of serious adverse reactions following transfusions reported to the Paul‐Ehrlich‐Institut were evaluated on the basis of national criteria, and the definitions of International Society of Blood Transfusion (ISBT) in compliance with defined causality criteria. The suspected cases were rated as confirmed and unconfirmed transfusion reactions. Assessment of causality took into consideration the clinical course of the adverse reaction and, if necessary, information about donation and manufacturing. Of the 5128 suspected serious adverse reactions, 1603 could be confirmed. Referring to the absolute figures, acute transfusion reactions (e.g. allergic reactions, hypotension and dyspnoea) were recorded most frequently, followed by transfusion‐related acute lung injury (TRALI), haemolytic reactions, transfusion‐related bacterial infections and virus infections. The majority of the 52 transfusion‐related fatalities (14 each) were due to TRALI and acute transfusion reactions (mostly severe allergic reactions). Referred to the blood products administered, immune TRALI cases and TRALI‐related fatal courses were most frequently reported after administration of fresh frozen plasma (FFP) (15/10⁶ and 3.5/10⁶ units, respectively), transfusion‐related bacterial infections after administration of platelet concentrates (7/10⁶ units), acute haemolytic transfusion reactions after administration of red blood cell concentrates (2.3/10⁶units) and acute transfusion reactions after administration of red blood cell or platelet concentrates (7.8/10⁶ and 13/10⁶ units, respectively). Despite the high safety standard required for blood products in Germany, there is still room for reducing the frequency of isolated cases of transfusion reactions by targeted action.     

Transfusion-related acute lung injury during plasma exchange: Suspecting the unsuspected

Transfusion-related acute lung injury (TRALI) has been implicated with use of almost all types of blood products that contain variable amounts of plasma. Even though the reported incidence of TRALI is rare, its overall occurrence is thought to be more common, as less severe cases remain unreported. More TRALI cases are unrecognized and misdiagnosed due to lack of suspicion and absence of appropriate investigation. There are exceedingly rare reports of TRALI during plasma exchange despite the fact that liters of plasma may be used for replacement during a single procedure. We describe a mild case of TRALI during plasma exchange for thrombotic thrombocytopenic purpura in a 56-year-old woman, status post autologous hematopoietic stem cell transplant for non-Hodgkin's lymphoma. She developed severe rigors, peripheral cyanosis, hypoxia, and a transient diffuse pulmonary infiltrate. Of the 10 U of plasma used, one was from a multiparous female donor with HLA antibodies reactive with patient's granulocytes in immunofluorescence and agglutination assays. This case emphasizes the fact that the physicians and apheresis staff should consider TRALI in the differential diagnosis for patients developing respiratory distress during or soon after the procedure. Diagnosing TRALI has implications not only for the plasma exchange recipient, but also for the management of donors found to have leukocyte antibodies.     

Transfusion-related acute lung injury: a thrombotic thrombocytopenic purpura treatment-associated case report and concise review

Blood products are frequently required immediately prior to, during, or just after an apheresis procedure. Transfusion-related acute lung injury (TRALI) is now the leading cause of transfusion-related mortality, surpassing ABO-incompatible hemolytic reactions. The reported incidence of TRALI varies but is estimated at 1 in 5,000 transfusions. The true incidence could be higher because of under-reporting and under-diagnosis. Plasma is the most frequently implicated blood product. While the pathogenesis of TRALI appears multifactorial, one contributing factor seems to be donor antibodies to cognate recipient neutrophil antigens. Biologically active neutrophil-priming substances may also play a role. New diagnostic criteria have recently been proposed to aid in the diagnosis of TRALI. We report a thrombotic thrombocytopenic purpura (TTP) treatment-associated case of TRALI and review the history, pathogenesis, diagnosis and management of this syndrome. Current risk reduction strategies are also discussed.     

Acute Respiratory Failure during Routine Blood Transfusion: A Case Report and Review of the Literature

Background

Transfusion medicine is a common practice in the emergency department (ED) and other outpatient settings, and may be complicated by a low rate of potentially fatal transfusion-related reactions.

Objectives

This article presents a case of transfusion-related acute lung injury (TRALI) diagnosed and treated in the ED and reviews the differential diagnosis of acute transfusion reactions.

Case Report

A 74-year-old woman presented to the ED from the hospital's transfusion center with fever and respiratory distress immediately after the start of her second unit of red blood cell transfusion. Chest radiograph demonstrated a pattern consistent with acute respiratory distress syndrome (ARDS). After 48 h of respiratory support and antibiotic therapy, the patient's condition improved.

Conclusion

TRALI is a clinical diagnosis with presentation similar to that of ARDS. Prompt differentiation from other transfusion reactions and initiation of appropriate treatment is crucial in minimizing the morbidity and mortality associated with this syndrome.     

血小板输注无效患者血小板同种抗体及血小板特异性糖蛋白抗体表达的研究

目的 探讨血小板输注无效与血小板同种抗原或血小板特异性抗原的相关性.方法 选择65例临床确诊血小板输注无效患者作为研究对象,应用酶联免疫吸附实验(ELISA)方法检测血清、血小板洗脱液中血小板特异性抗体;应用HLA抗体特异性检测试剂盒,对组合反应性抗体(PRA)阳性的患者进行HLA抗体特异性分析;用HPA分型试剂盒检测8个血小板同种抗原系统HPA-1、2、3、4、5、6、9、15;用HLA分型试剂盒对HLA-A/B抗原进行基因分型.结果 65例患者HLA-A/B抗原,HPA-1、2、4、5、6、9、15抗原的基因频率分布与健康献血员比较差异无统计学意义.HPA-3a、3b抗原频率分别为0.65、0.35,与健康献血员比较差异有统计学意义(P＜0.05).65例患者中HLA抗体单独阳性24例(36.9%),HLA抗体和血小板特异性糖蛋白抗体共同阳性14例(21.5%);HLA抗体和血小板洗脱液特异性糖蛋白抗体共同阳性6例(9.2%),血小板洗脱液特异性糖蛋白抗体阳性13例(20%),HLA抗体、血小板特异性糖蛋白抗体及血小板洗脱液特异性糖蛋白抗体共同阳性4例(6.2%);HLA-A/B特异性抗体中,HLA-A*9抗体占全部抗体的46.2%,HLA-B*40抗体占33.6%.血清血小板特异性抗体以GPⅡb/Ⅲa为主(26.2%),其次为GP Ⅰa/Ⅱa(21.5%),血小板洗脱液中,血小板特异性抗体以GPⅡb/Ⅲa和GP Ⅰb/Ⅸ为主(41.5%).对2例患者进行了遗传学调查,发现产生的血小板特异性糖蛋白抗体和HLA抗体与父母血小板抗原及HLA抗原不相合呈密切相关.结论 血小板输注无效患者中,HLA抗体占主要地位,其次为血小板特异性糖蛋白抗体.     

Ibrutinib‐associated bleeding: pathogenesis,management and risk reduction strategies

Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase (Btk) that has proven to be an effective therapeutic agent for multiple B‐cell‐mediated lymphoproliferative disorders. Ibrutinib, however, carries an increased bleeding risk compared with standard chemotherapy. Bleeding events range from minor mucocutaneous bleeding to life‐threatening hemorrhage, due in large part to the effects of ibrutinib on several distinct platelet signaling pathways. There is currently a minimal amount of data to guide clinicians regarding the use of ibrutinib in patients at high risk of bleeding or on anticoagulant or antiplatelet therapy. In addition, the potential cardiovascular protective effects of ibrutinib monotherapy in patients at risk of vascular disease are unknown. Patients should be cautioned against using non‐steroidal anti‐inflammatory drugs, fish oils, vitamin E and aspirin‐containing products, and consider replacing ibrutinib with a different agent if dual antiplatelet therapy is indicated. Patients should not take vitamin K antagonists concurrently with ibrutinib; direct oral anticoagulants should be used if extended anticoagulation is strongly indicated. In this review, we describe the pathophysiology of ibrutinib‐mediated bleeding and suggest risk reduction strategies for common clinical scenarios associated with ibrutinib.     

Hypotension and acute pulmonary insufficiency following transfusion of autologous red blood cells during surgery: a case report and review of the literature

Transfusion of autologous blood is associated with fewer complications, although all untoward events of transfusion may not be negated with this strategy. We report a case of acute pulmonary insufficiency and hypotension following transfusion of autologous packed red blood cells (PRBCs) in a patient, who was undergoing major surgery. Anti-HLA class-I and class-II and anti-granulocyte antibodies were measured in the unit and in the recipient. Neutrophil (PMN)-priming activity was measured as the augmentation of the formyl-Met-Leu-Phe-activated respiratory burst. No immunoglobulins were identified; however, significant lipid-priming activity was present in the implicated, autologous PRBC unit that primed PMNs from both healthy people and the recipient. In addition, lipids, identical to those that accumulate during PRBC storage, caused significant hypotension when infused into rats at similar concentrations found in stored PRBCs. We conclude that the observed transfusion-related acute lung injury reaction with significant hypotension may be the result of two independent events: the first is related to inherent host factors, in this case major surgery, and the second is the infusion of lipids that accumulate during the routine storage of PRBCs.     

针对人类白细胞抗原的抗体对造血干细胞移植预后的影响及其临床干预措施

人类白细胞抗原(HLA)抗体产生于同种异体免疫过程,如妊娠、输血、异基因移植、感染、接触致敏原等.HLA抗体已被公认为是影响实体器官移植预后的重要免疫因素,近年来,多项研究结果表明HLA抗体亦为造血干细胞移植(HSCT)预后的不良影响因素,因此积极进行HLA抗体筛查及早期干预对改善HSCT预后具有重要意义.笔者拟就目前HSCT领域中HLA抗体相关研究进展及其干预治疗方案进行综述.     

常见输液不良反应原因分析及护理对策

[目的]探讨常见输液不良反应发生的原因,并提出相应的护理对策.[方法]回顾性分析输液不良反应发生的临床资料.[结果]输液不良反应主要包括药物不良反应、晕针反应、静脉炎、热源反应等.[结论]预见性的观察和针对性的护理干预是减少输液不良反应的重要措施.