1、TRANSFUSION RISKS(NON-INFECTIOUS)Hua Shan,M.D.,Ph.DJohns Hopkins Medical InstitutionsBaltimore,Maryland,USA输血风险（非感染性）华山 M.D.，Ph.D约翰 霍伯金斯医学院美国，马里兰州，巴尔的摩危 险 肝炎 同种致敏作用 循环超负荷 过敏反应 败血症InfectionsUSA Non-infectiousUSAHIV1/1.9 millionDeath:acute hemolytic1:600,000(New York 1990-1991)HCV1/1.8 millionHBV1/205
2、,000感染性USA USA 非感染性USAUSAHIV1/190万万死亡：死亡：急性溶血急性溶血1:600,000(New York 1990-1991)HCV1/180万万HBV1/205,000Transfusion ReactionsPotentially severe TR:Hemolytic TRAnaphylactic TRTransfusion-related Acute Lung Injury Circulatory overloadSeptic TRTransfusion-associated Graft-vs-Host Disease 输血反应(TR)潜在的严重输血反应：
3、溶血输血反应过敏性输血反应输血相关性急性肺损伤 循环超负荷败血症输血相关性移植物抗宿主病Transfusion ReactionsCommon and usually mild:Febrile nonhemolytic TRMild allergic TR(Circulatory overload)Acute pain TR输 血 反 应 常见的，通常轻度的输血反应：非溶血性发热输血反应轻度过敏输血反应（循环超负荷）急性疼痛Hemolytic TRCause:Immunological incompatibility between donor and recipient ABO,Rh,oth
4、er RBC alloantigens Mechanism:Antibody mediated destruction of RBC (Non-immune-mediated hemolysis:Wrong infusion fluid,wrong needle size,or incorrect use of blood warmer,etc)溶血性输血反应原因：原因：捐献者和受者之间的免疫不相容性，ABO，Rh和其它红细胞血型同种抗原机制机制：抗体介导的红细胞破坏非免疫介导的溶血：非免疫介导的溶血：输液错误、针的大小错误或血液不当预热等等）Subtypes of Hemolytic TRA
5、cute(AHTR)vs.Delayed(DHTR)TimeHemolysis Antibody Acute:24hr Extravascular Rh/others(IgG)溶血性输血反应 急性溶血性输血反应对比迟发性溶血性输血反应 时间 溶血 抗体 急性 24hr 血管外 IgG类抗体ANTIBODY-MEDIATED HEMOLYSIS IgM antibodies are typically naturally occurring,best example is the ABO system IgG antibodies are typically alloantibodies ind
6、uced by pregnancy or transfusions;best example is the Rh system.抗体介导的溶血 IgM抗体是典型的天然存在的血型抗体，最好的例子是ABO血型系统n IgG抗体是典型的同种抗体，由怀孕或输血诱导产生的；最好的例子是Rh血型系统ABO Antigens Critical Role in Transfusion High antigen density on red cells Reciprocal arrangement whereby patients who are group A have naturally occurring
7、 anti-B in their serum.ABO antibodies are high titer IgM antibodies which produce intravascular hemolysis Group O is universal donor;group AB is universal recipientABO抗原 输血中的重要角色 红细胞上的高密度抗原 有A抗原的病人的血清中天然存在抗-B ABO抗体是高滴度的IgM抗体，它们会造成血管内溶血 O型血是万能献血者，AB型是万能受血者Rh BLOOD GROUP 1939-Levine and Stetson report
8、 case of mother of a stillborn who suffered severe HTR after transfusion of husbands blood.1940-Landsteiner and Wiener immunized rabbits with rhesus cells and found sera that agglutinated cells from 85%of NYC donors 1941-Levine confirmed association between Rh incompatibility and HDNRh血型 1939年 Levin
9、e和Stetson报道了一例出现死胎的母亲在输注了丈夫的血液后发生严重溶血性输血反应 1940年 Landsteiner和Wiener用恒河猴的细胞免疫兔子，发现其血清能与85%的纽约市献血者血液发生凝集 1941年 Levine证实 Rh不相容性和新生儿溶血病之间存在联系Rh Antigens Clinical Importance Immunogenicity:strong High frequency of incompatibilityRhD:85%positive,15%negative(USA).D c E Major problem in US for transfusion r
10、ecipients Prior to RhIg,major cause of hemolytic disease of the newbornRh抗原 临床重要性 免疫原性：强免疫原性：强 RhD：85%阳性，15%阴性（美国）D c E 成为美国受血者的主要问题 在RhIg之前是新生儿溶血病的主要原因Other Red Cell Antigens At least 300 blood groups have been described.Many antibodies are clinically significant,causing hemolysis and transfusion r
11、eactions.Other antibodies can cause serologic incompatibility but do not affect red cell survival clinically insignificant Antibodies causing transfusion reactions vary among populations depending upon antigen frequencies其他红细胞抗原 已报道至少有300种血型抗原 很多抗体具有临床意义，会造成溶血和输血反应 其他抗体可能造成血清学不相容性，但不会影响红细胞存活无临床意义 抗体
12、造成的输血反应在不同人群中不同，其主要依赖于抗原频率Prevention of Hemolytic TR At sample collection:Correct patient and sample identification Pre-transfusion Testing ABO/RH antigen and antibody Unexpected antibodies Before transfusion:correct patient and unit identification During and after transfusion:close monitoring of pa
13、tients溶血输血反应的预防 标本的采集：确认病人和标本正确无误 输血前实验室检查-ABO/Rh-ABO/Rh抗原和抗体抗原和抗体-不规则抗体不规则抗体 输血前：确认病人和输血量的正确无误 输血中和输血后：密切观察病人PRETRANSFUSION TESTING Verify patient identity Determine ABO and Rh Perform antibody screen(to detect unexpected antibodies)Perform compatibility test-final verification输血前实验前实验 核实病人身份 确定ABO
14、和Rh血型 进行抗体筛查（检测不规则抗体）相容性试验最后确认表1 标本贴签要求和拒绝标准 要求 手写标签符合申请表资料 病人全名 病人住院的身份号 绝对拒绝 有证据显示贴标签不是在床边完成 打印或自动生成的标签 名字错误或没有 姓错误或没有 没有病人的住院身份号 身份号超过1个数字有误，除非只有2 位数，数字顺序颠倒 脐带样本没有标明“脐带”或“婴儿”或“男孩/女孩”难以执行 只有首写字母，罕见的姓氏 手写标签在自动标签上 样本标签符合臂章，但与申请表的资料不符可接受 名字错误但可以理解，或者两个名字 姓有细微的拼写错误 病人身份号的一个数字错误或两个数字颠倒；罕见名字 抽取血标本的病人的住院
15、病房、床号和日期必须写在标本的标签上或是输血申请单上 不良事件的报告和咨询表2：ABO和/或Rh血型错误的频率 标本 标本分型 错误 百分比正确标签 40,274 14 0.035错误标签（拒绝）496 7 1.4Elements of a Compatibility Testing SystemElements of a Compatibility Testing System Patient identification Sample identification ABO/Rh/Ab screen Records check Unit selection Crossmatching Lab
16、eling Recipient identification Patient identification Sample identification ABO/Rh/Ab screen Records check Unit selection Crossmatching Labeling Recipient identification 1/2,900 samples contains blood from the wrong patient1/2,900 samples contains blood from the wrong patient Lumadue JA et al.Transf
17、usion 1997;37:1169-72.Lumadue JA et al.Transfusion 1997;37:1169-72.相容性试验的组成元素确认病人确认标本 抽错血标本的几率是1/2900确认受者Acute Hemolytic ReactionsSigns and Symptoms Fever and chills81%Rigors Anxiety,feeling of doom Facial flushing Abdominal,back,or flank pain Nausea and vomiting 12%Dyspnea 7%Hypotension/tachycardia
18、 12%Pain at infusion site 16%Oliguria/anuria 36%Diffuse bleeding(DIC)8%急性溶血反应体征和症状 发热发寒 僵直 焦急、感觉不幸 脸发红 腹、背或腰疼 头晕、恶心 呼吸困难 低血压/心动过速 输血部位疼痛 尿少/无尿 弥漫性出血(DIC)81%12%7%12%16%36%8%溶血性输血反应的治疗1、停止输血2、维持静脉通路3、开始利尿4、输液5、维持血压6、监测肾功能 7、监测凝血状态 8、避免输注抗原阳性血 溶血性输血反应的调查 1、停止输血2、取血样3、检查是否有笔误4、进行直接抗球蛋白试验 5、观察血浆的溶血状况或黄疸6
19、、如果怀疑溶血反应，重复相容性实验Laboratory InvestigationsBlood ProductConfirm ABO,Rh Confirm other antigensBlood Bank LaboratoryDirect antiglobulin testConfirm ABO,A/S,patient IDLook for hemolysisClinical LaboratoryComplete blood countBilirubin,creatinineDIC evaluation实验室调查血液制品确认ABO，Rh血型确认其他血型抗原血库实验室直接抗球蛋白试验确认ABO，
20、A/S，病人身份寻找溶血症临床实验室全血计数胆红素，肌酐，弥漫性血管内凝血评估TherapyGeneralRenalPulmonaryDICVenous accessMaintain BP and urine outputMonitorPulmonaryFunctionConsider HeparinVital signsDiureticsOxygenPlateletsICU DopamineVentilatorFFPPulmonaryArtery cathDialysis治治 疗疗总的总的肾的肾的肺的肺的弥漫性弥漫性血管内凝血血管内凝血静脉途径维持血压和排尿监测肺功能考虑肝素重要信号利尿剂氧
21、血小板重症监护多巴胺呼吸器新鲜冰冻血浆肺动脉导管 透析AHTRSUMMARY ABO Incompatible blood is the most common cause Intravascular hemolysis can lead to fever,shock,renal failure,DIC.Clerical errors and wrong blood in tube are the major cause:(51%of 355 reported deaths in 100 million units 1976-1985)急性溶血性输血反应小结 ABO不相容是溶血最常见的原因 血
22、管内溶血会导致发热、休克、肾衰、弥漫性血管内凝血 书写错误和血标本错误是主要原因：（1976-1985年间，1亿单位输血量355例死亡报导中51%是由此造成）Hemoglobin Level Change During DHTRHemoglobin Level Change During DHTR*Many patients may be asymptomatic血管外溶血性输血反应 n症状：l虚弱l不舒服l头疼n体征l红细胞压积降低l黄疸（高胆红素血症）l发热l直抗试验阳性*很多病人可能没有症状DHTR-Criteria Pre-transfusion:Negative pretransfu
23、sion antibody screenNegative crossmatchPost-transfusion:Crossmatch with post-transfusion serum becomes positiveAlloantibody detectedClinical and laboratory evidence of hemolysis Past history of pregnancy or transfusions延迟性溶血性输血反应诊断标准输血前：输血前抗体筛查阴性交叉配血试验阴性输血后：用输血后的血清进行交叉配血试验呈阳性检测到同种抗体 临床和实验室证明溶血 既往有怀孕
24、或输血史DHTR-Laboratory Findings Unexplained anemia Positive direct antiglobulin test(DAT)Antibody in posttransfusion RBC eluate:Non-ABO RBC alloantibodies延迟性溶血性输血反应实验室发现 无法解释的贫血 直抗阳性 输血后红细胞洗出液存在抗体：非-ABO红细胞同种抗体Antibodies Implicated in DHTRJohns Hopkins series Anti-E 47%Anti-Jka 23%(clinically important)
25、Anti K 15%延迟性溶血性输血反应中的抗体霍普金斯医院资料 抗-E 47%抗-Jka 23%（临床意义）抗-K 15%DHTR TimelineTIME(DAYS)EVENTCAUSE0Negative testsAntibody not detectable1RBCs given3-10Clinical hemolysisAccelerated RBC destruction10-21Positive DAT and A/S detectedAntibody titer increases and sensitizes cells21DAT negativeSensitized don
26、or cells cleared延迟性溶血性输血反应时间表天事件原因0 试验阴性抗体不可被检测1RBCs given3-10临床溶血红细胞破坏加速 10-21直抗阳性，监测到A/S抗体滴度增加，细胞致敏21直抗阴性捐献者致敏细胞被清除DHTR Prevention Improved patient care by developing mechanism to identify patients,counsel them about future transfusions,provide early warnings to health care providers.Prevention wi
27、th careful transfusion history,registries of alloimmunized patients延迟性溶血性输血反应的预防 通过对病人身份鉴定、和他们商讨未来的的输血，对健康看护者提供早期警告来改进对病人的照顾 对同种免疫的病人备案，仔细询问既往输血史 预防延迟性溶血性输血反应Typical sequence of chest X-rays changes:Left:Normal CXR prior to transfusionMiddle:2 hrs posttransfusion,showing bilateral pulmonary infiltra
28、tes c/w pulmonary edemaRight:48 hours posttransfusion,showing clearing of pulmonary infiltratesChest X-ray in a post-transfusion patient一名病人输血后的胸片一名病人输血后的胸片典型的胸片改变左图输血前正常胸片中图输血后2小时显示肺两侧有浸润，肺水肿右图输血后48小时显示肺浸润清除Transfusion Related Acute Lung Injury(TRALI)Acute Lung Injury(ALI)Acute onset of hypoxiaBila
29、teral infiltrates on chest X-rayFever,mild hypotensionHappens within 6 hours of transfusionPlasma containing product(FFP,Plt,RBC)Rule out other reasons for ALISepsis,pneumonia,DIC,aspiration etcTRALI can cause patient deathThe#1 cause for transfusion related dealth in USA in 2001-2003输血相关性急性肺损伤急性肺损伤
30、组织缺氧急性发作透双侧浸润发热、轻度低血压输血后6小时内发生 血浆含有血制品（新鲜冰冻血浆、血小板、红细胞）排除其他急性肺损伤原因败血症、肺炎、弥漫性血管内凝血、吸入等输血相关急性肺损伤可使病人死亡是2001-2003年美国输血相关死亡的首位原因。TRALI-Differential DiagnosisAnaphylactic Transfusion ReactionCirculatory OverloadBacterial contaminationTRALI的鉴别诊断n过敏性输血反应n循环量超负荷n细菌污染TRALI-Mechanism Immunological reactionAnti
31、bodies to white cellsanti-HLA or granulocyte specific Usually in donorsLess often in recipientsTRALI发生机制免疫学反应白细胞的抗体抗-HLA或粒细胞特异性抗体通常在献血者中在受血者中不常见TRALI-Prevention Prevention:Exclude multiparous donors from plasma donoation(UK)Minimize the use of high-plasm-volume products from leukocyte-alloimmunized
32、donors(US)TRALI预防预防：不用经产妇血浆（英国）最小限度地使用白细胞同种免疫的捐献者的高血浆量的血制品TRALI-Treatment Respiratory support:Oxygen supplementationIntubation/mechanical ventilationMost patients improve clinically within 48-96 hrs if treated promptlyTRALI治疗呼吸支持：补充氧插管法/机械换气大部分病人如果治疗迅速在 48-96小时内临床缓解TRALI Summary Pulmonary leukoagglu
33、tination syndrome Reaction to donor antibodies against recipient white cells Respiratory distress,hypoxia,pulmonary edema,5 to 8%mortality Intubation,100%O2,defer donors Reactions more likely with larger quantities of plasma from multiparous donorsTRALITRALI小结小结 肺白细胞凝集综合症 受者白细胞对捐献者抗体的反应 呼吸困难、组织缺氧、肺水
34、肿、5-8%死亡率 插管法、100%O2、捐献者延期献血 反应大多是由于输注大量经产妇献血者的血浆造成Transfusion Associated Circulatory Overload(TACO)Congestive heart failure cause by transfusionDiminished cardiac reservePre-transfusion fluid overloadIV infusion,chronic anemia etcEspecially in old or very young patientsRapid infusion or massive tra
35、nsfusionSymptoms caused by acute pulmonary edema:Dyspnea,tachycardia,orthopenea,BP increase,cyanosis,pulmonery/pedal edema输血相关性循环超负荷输血造成的充血性心衰 心力储备降低输血前输液过量静脉注射、慢性贫血等 特别是老年人和小年龄病人快速或大量输血急性肺水肿造成的症状：呼吸困难、心动过速、端坐呼吸、血压增高、紫绀、肺/下肢水肿TACO-Differential diagnosisTRALI Hypotension Pulmonary wedge pressure norm
36、al or low Chest x-ray Anaphylaxis Rapid onset(seconds to minutes)Erythmatous confluent rashSevere hypotensionNo pulmonary edemaBacterial contamination Fever Hypotension循环超负荷鉴别诊断急性输血相关性肺损伤 低血压 肺楔压正常或偏低 胸透过敏反应快速发作红斑综合性皮疹严重的低血压无肺水肿细菌污染发热 低血压TACO-PreventionIdentify susceptible patients:Old,young,history
37、 of heart disease,fluid overload,chronic anemia etcSlow infusion:1 ml/kg body weight/hour Concentrate componentsSplit a component Close monitoring of symptoms循环超负荷预防确定易感者：年老、小病人、有心脏病史、输液过量、慢性贫血等输血速度减慢每公斤体重每小时输1ml血 浓缩成份分离血液成份密切监测症状 SEPTIC REACTIONS Microbial contamination Fever(hours),shock,hypotensi
38、on Gram stain,bacterial culture Platelets(room temp storage)Red cell reactions less common but often due to Yersinia infection败 血 症 微生物污染微生物污染 发热、休克、低血压发热、休克、低血压 革兰氏染色、细菌培养革兰氏染色、细菌培养 血小板（室温保存）血小板（室温保存）红细胞反应少见，但经常是由于耶尔森氏菌感染红细胞反应少见，但经常是由于耶尔森氏菌感染Transfusion-Associated GVHD Classic GVHD symptoms:diarrhe
39、a,skin rash,hepatitis Bone marrow failure-aplastic anemia common with TA-GVHD Death(infection)2 to 3 weeks post transfusion输血相关的移植物抗宿主病 经典的症状：痢疾、皮疹、肝炎 骨髓衰竭再生障碍性贫血常见于是输血相关的移植物抗宿主病 输血后2-3周死亡（死于感染）PATIENTS AT RISK for TA-GVHDIn-utero transfusionsYoung childrenPatients with congenital immunedeficiencyPa
40、tients with acquired immunosuppressionCancerImmunesuppressive therapy Recipients of related donor blood存在有输血相关的移植物抗宿主病风险的病人 子宫内的输血 年幼儿童 有先天免疫缺陷的病人 有获得性免疫抑制、癌症、接受免疫抑制治疗的病人 亲缘性输血的受血者Prevention of TA-GVHD:IRRADIATED BLOOD Irradiation at the correct dose destroys lymphocytes ability to reproduce,therefo
41、re eliminate risk of TA-GVHD Luokoreduction is NOT sufficient,because a very small number of live lymphocytes can still cause TA-GVHDTA-GVHDTA-GVHD预防预防 血液辐照l适当剂量的辐照损坏白细胞的再生能力，因此可减少输血相关移植物抗宿主病的风险l去白是不够的，因为非常少量的活的白细胞仍旧可以造成输血相关移植物抗宿主病FEBRILE,NON-HEMOLYTIC REACTIONS Temperature elevation 1 C WBC antibod
42、ies in patient serum reacting with donor WBC or platelets Cytokines generated by stored WBC Must be distinguished from hemolytic and septic reactions非溶血的发热反应 温度升高1C 病人血清中的白细胞抗体与捐献者的白 细胞或血小板反应 储存的白细胞产生细胞因子 必须与溶血反应和败血症区别FEBRILE,NON-HEMOLYTIC REACTIONS Preventable by use of leukoreduced blood component
43、s May be applied for selected patients with previous reactions or universally to prevent reactions in all patients Pre-medication:Tylenol Washing components may also help to remove cytokines or white cells from blood components非溶血性发热反应 通过使用去白血液制品可以预防 去白血制品可用于以前有反应的病人或者普遍用于 预防输血反应 输前用药：羟苯基乙酰胺 血液成份洗涤也
44、可有助于去除细胞因子或白细胞病理n免疫介导的组胺的释放处理n抗组胺剂n类固醇（严重）n肾上腺素（严重）n洗涤红细胞（抗-IgA）过 敏 反 应ALLERGIC REACTIONS Hypersensitivity(IgE)response to donor plasma proteins;hives,flushing,tachycardia are most common signs and symptoms Bronchospasm or anaphylaxis can occur,often with IgA deficiency Benadryl,corticosteroids,conc
45、entrated or washed products Most common cause of transfusion reaction,particularly with products containing plasma过敏反应 对捐献者的血浆蛋白超敏反应（IgE），麻疹、脸红、心动过速都是常见的体征和症状 会发生支气管痉挛或过敏反应，常常IgA缺乏 二苯醇胺、皮质类固醇，浓缩或洗涤血液产品 是最普遍的输血反应的原因，特别是含血浆的血制品Massive TransfusionDefinition:Receiving 10 units of blood(replacing one blo
46、od volume)in 24 hours:Replacing 50%of the circulating blood volume in 10U血液：在3小时内置换了50%循环血量通常发生在：外伤、主动脉瘤破裂、严重的出血（胃肠道、外科手术中等）Massive Transfusion-ComplicationsHypothermiaHemostatic abnormalities Dilutional coagulopathyDICMetabolic abnormalitiesCitrate toxicity(citrate delivery livers capacity for clea
47、rance)Hypocalcemia and hypomagnesemia Acid-base balance metabolic alkalosisHyperkalemia大量输血并发症体温降低止血异常稀释凝血障碍弥漫性血管内凝血代谢异常柠檬酸中毒（柠檬酸传递肝脏清 除能力）低钙和低镁血症酸碱平衡代谢性碱中毒高血钾症Prevention of Complications During Massive TransfusionUse of a blood warmerClose monitoring of patient signs/symptoms and lab resultsUse Typ
48、e O,Rh-red cells and type AB plasma Correct citrate toxicity,acid-base imbalance and hemostatic abnormalities在大量输血中预防并发症血液预温密切监控病人的体征/症状和实验室结果使用O型Rh红细胞和AB型血浆 纠正柠檬酸中毒、酸碱不平衡和止血异常Complications of Neonatal TransfusionImpaired glucose homeostasis:Hypoglycemia Hypocalcemia HyperkalemiaSusceptibility to ci
49、rculatory overload,TA-GVHD and other complications 新生儿输血并发症削弱的血糖稳态：低血糖 低血钙 高钾 对循环过载敏感，输血相关移植物抗宿主病和其他并发症Neonatal Transfusion-Prevention of ComplicationsIrradiated bloodLeukoreduced bloodFresh blood or washed bloodClose monitoringVolume,metabolic changes新生儿输血并发症的预防血液辐照血液去白新鲜血液或洗涤血液密切监视血容量和代谢改变 CONCLUS
50、IONS Many adverse effects of transfusion can be directly attributed to errors at the blood center,errors in the transfusion service,or errors in the hospital or clinic.Recognizing transfusion reactions and trying to fix these errors can prevent further reactions in other patients.Evolving blood comp
