输血风险非感染性.ppt

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1、TRANSFUSION RISKS (NON-INFECTIOUS),Hua Shan, M.D., Ph.D Johns Hopkins Medical Institutions Baltimore, 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,Risks of Transfusion: infectious vs. non-infectious,输血风险：感染性对比非感染性,Transfusion Reactions,Potentially severe

2、 TR: Hemolytic TR Anaphylactic TR Transfusion-related Acute Lung Injury Circulatory overload Septic TR Transfusion-associated Graft-vs-Host Disease,输血反应(TR),潜在的严重输血反应： 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 Reactions,Common and usually mild: Febrile nonhemolytic TR Mild allergi

3、c 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 TR,Cause: Immunological incompatibility between donor and recipient ABO, Rh, other RBC alloantigens Mechanism: Antibody mediated destruction of RBC (Non-immune-mediated hemolysis: Wrong infusi

4、on fluid, wrong needle size, or incorrect use of blood warmer, etc),溶血性输血反应,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： 抗体介导的红细胞破坏 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 TR Acute (AHTR) vs. Delayed (DHTR),Time Hemolysis Antibody Acute: 24hr Extravascular Rh/others(IgG),溶血性输血反应 急性溶血性输血反

5、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 induced 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

6、血型系统 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 anti-B in their serum. ABO antibodies are high titer IgM antibodies which produce intravascular hem

7、olysis Group O is universal donor; group AB is universal recipient,ABO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 case of mother of a stillborn who suffered severe HTR after transfusion of husbands blood. 194

8、0- 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 HDN,Rh血型,1939年 Levine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%

9、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 incompatibility RhD: 85% positive, 15% negative (USA). D c E Major problem in US for transfusion recipients Prior to RhIg, major cause of hemolytic disease of the newborn,Rh抗原 临床

10、重要性,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 reactions. Other antibodies can cause serologic incompatibility but do not affe

11、ct 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:

12、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 patients,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抗原和抗体 -不规则抗体 输血前：确认病

13、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,核实病人身份 确定ABO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

14、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,

15、274 14 0.035 错误标签（拒绝） 496 7 1.4,Elements of a Compatibility Testing,System,Elements of a Compatibility Testing,System, Patient identification, Sample identification, ABO/Rh/Ab screen, Records check, Unit selection, Crossmatching, Labeling, Recipient identification, Patient identification, Sample ide

16、ntification, ABO/Rh/Ab screen, Records check, Unit selection, Crossmatching, Labeling, Recipient identification,1/2,900 samples,contains blood from,the wrong patient,1/2,900 samples,contains blood from,the wrong patient,Lumadue JA,et al. Transfusion,1997;37:1169-72.,Lumadue JA,et al. Transfusion,199

17、7;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 Reactions Signs and Symptoms,Fever and chills 81% Rigors Anxiety, feeling of doom Facial flushing Abdominal, back, or flank pain Nausea and vomiting 12% Dyspnea 7% Hypotension/tachycardia 12% Pain at infusion site 16% Oliguria/a

18、nuria 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、如果怀疑溶血反应 ，重复相容性实

19、验,Laboratory Investigations,实验室调查,Therapy,治 疗,AHTR SUMMARY,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

20、溶血性输血反应小结,ABO不相容是溶血最常见的原因 血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 DHTR,Hemoglobin Level Change During DHTR,*Many patients may be asymptomatic,血管外溶血性输血反应,症状： 虚弱 不舒服 头疼 体征 红细胞压积降低 黄疸（高胆红素血症） 发热 直抗试验阳性 *很多病人可能没有症状,DHTR- Criteria,Pr

21、e-transfusion: Negative pretransfusion antibody screen Negative crossmatch Post-transfusion: Crossmatch with post-transfusion serum becomes positive Alloantibody detected Clinical 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

22、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 DHTR Johns Hopk

23、ins series,Anti-E 47% Anti-Jka 23% ( clinically important) 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 Timeline,延迟性溶血性输血反应时间表,DHTR Prevention,Improved patient care by developing mechanism to identify patients, counsel them about future transfusions, provide early warnings

24、 to health care providers. Prevention with 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 transfusion Middle: 2 hrs post

25、transfusion, showing bilateral pulmonary infiltrates c/w pulmonary edema Right: 48 hours posttransfusion, showing clearing of pulmonary infiltrates,Chest X-ray in a post-transfusion patient,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 (T

26、RALI),Acute Lung Injury (ALI) Acute onset of hypoxia Bilateral infiltrates on chest X-ray Fever, mild hypotension Happens within 6 hours of transfusion Plasma containing product (FFP, Plt, RBC) Rule out other reasons for ALI Sepsis, pneumonia, DIC, aspiration etc TRALI can cause patient death The #1

27、 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 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 Diagnosis,Anaphylactic Transfusion Reaction Circulatory Overload Bacterial

28、contamination,TRALI的鉴别诊断,过敏性输血反应 循环量超负荷 细菌污染,TRALI-Mechanism,Immunological reaction Antibodies to white cells anti-HLA or granulocyte specific Usually in donors Less often in recipients,TRALI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 fr

29、om plasma donoation (UK) Minimize the use of high-plasm-volume products from leukocyte-alloimmunized 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 supplementation Intubation / mechanical ventilation Most patients improve clinically within

30、 48-96 hrs if treated promptly,TRALI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 leukoagglutination syndrome Reaction to donor antibodies against recipient white cells Respiratory distress, hypoxia, pulmonary edema, 5 to 8 % mortality Intubation, 100% O2, defer donors Reac

31、tions more likely with larger quantities of plasma from multiparous donors,TRALI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 transfusion Diminished cardiac reserve Pr

32、e-transfusion fluid overload IV infusion, chronic anemia etc Especially in old or very young patients Rapid infusion or massive transfusion Symptoms 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

33、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 diagnosis,TRALI Hypotension Pulmonary wedge pressure normal or low Chest x-ray Anaphylaxis Rapid onset (seconds to minutes) Erythmatous confluent rash Severe hypotension No pulmonary edema Bacterial contaminati

34、on 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-Prevention,Identify susceptible patients: Old, young, history of heart disease, fluid overload, chronic anemia etc Slow infusion: 1 ml/kg body weight/hour Concentrate components Split a component

35、 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, hypotension Gram stain, bacterial culture Platelets (room temp storage) Red cell reactions less common but often due to Yersini

36、a infection,败 血 症,微生物污染 发热、休克、低血压 革兰氏染色、细菌培养 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,Transfusion-Associated GVHD,Classic GVHD symptoms: diarrhea, 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

37、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-GVHD,In-utero transfusions Young children Patients with congenital immunedeficiency Patients with acquired immunosuppression Cancer Immunesuppressive 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

38、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, therefore eliminate risk of TA-GVHD Luokoreduction is NOT sufficient, because a very small number of live lymphocytes can still cause TA-GVHD,TA-GVHD预防 血液

39、辐照,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 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 antibodies in patient serum reacting with donor WBC or platelets Cytokines generated by stored WBC Must be distinguished from hemolytic and septic reactions,非溶

40、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 components May be applied for selected patients with previous reactions or universally to prevent reactions in all patients Pre-medication: Tylenol Washing co

41、mponents 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 血液成份洗涤也可有助于去除细胞因子或白细胞,病理 免疫介导的组胺的释放 处理 抗组胺剂 类固醇（严重） 肾上腺素（严重） 洗涤红细胞（抗-IgA）,过 敏 反 应,ALLERGIC REACTIONS,Hypersensitivity (IgE) response to donor plasma prote

42、ins; hives, flushing, tachycardia are most common signs and symptoms Bronchospasm or anaphylaxis can occur, often with IgA deficiency Benadryl, corticosteroids, concentrated 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（

43、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 Transfusion,Definition: Receiving 10 units of blood (replacing one blood volume) in 24 hours: Replacing 50% of the circulating blood volume in 3 hours Usually happens in: Trauma, ruptured aortic aneu

44、rysms, severe bleed (gastrointestinal, intraoperative, etc),大 量 输 血,定义 24小时内接受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-Complications,Hypothermia Hemostatic abnormalities Dilutional coagulopathy DIC Metabolic abnormalities Citrate toxicity (citrate delivery livers

45、 capacity for clearance) Hypocalcemia and hypomagnesemia Acid-base balance metabolic alkalosis Hyperkalemia,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 Transfusion,Use of a blood warmer Close monitoring of patient sign

46、s/symptoms and lab results Use Type 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 Transfusion,Impaired glucose homeostasis: Hypoglycemia H

47、ypocalcemia Hyperkalemia Susceptibility to circulatory 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 Complications,Irradiated blood Leukoreduced blood Fresh blood or washed blood Close monitoring Volume, metabolic

48、 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,CONCLUSIONS,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 components can reduce the residua