[荟萃]《溶血性贫血》课件.ppt

1、Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 溶血性贫血溶血性贫血Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 一、溶血性贫血发病机理一、溶血性贫血发病机理Our greatest weakness lies in giving up.The most cer

2、tain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies i

3、n giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time（一）（一）红细胞内在缺陷与红细胞外红细胞内在缺陷与红细胞外因素因素（二）先天性和后天获得性（二）先天性和后天获得性（三）血管内溶血与血管外溶血（三）血管内溶血与血管外溶血二、溶血病的分类二、溶血病的分类Our greates

4、t weakness lies in giving up.The most certain way to succeed is always to try just one more time 红细胞本身的异常：红细胞本身的异常：*酶缺陷酶缺陷 丙酮酸激酶缺乏症丙酮酸激酶缺乏症 葡萄糖葡萄糖-6-6-磷酸脱氢酶缺乏症磷酸脱氢酶缺乏症 *血红蛋白缺陷血红蛋白缺陷 结构异常结构异常:异常血红蛋白病异常血红蛋白病 生成异常生成异常:珠蛋白生成障碍性贫血珠蛋白生成障碍性贫血 (海洋性贫血海洋性贫血)*膜异常膜异常 先天：遗传性球形红细胞增多症先天：遗传性球形红细胞增多症 遗传性椭圆形红细胞增多症遗传性

5、椭圆形红细胞增多症 遗传性口形红细胞增多症遗传性口形红细胞增多症 遗传性带刺红细胞增多症遗传性带刺红细胞增多症 后天：阵发性睡眠性血红蛋白尿后天：阵发性睡眠性血红蛋白尿（一）红细胞内在缺陷与红细胞外因素（一）红细胞内在缺陷与红细胞外因素Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 红细胞外在因素所致红细胞外在因素所致：*抗体作用抗体作用 免疫性溶血性贫血免疫性溶血性贫血 自身免疫性：自身免疫性：温反应抗体温反应抗体AIHA(原

6、发性、继发性原发性、继发性)冷反应抗体冷反应抗体冷凝聚素病冷凝聚素病(原发性、继发性原发性、继发性)异体免疫性异体免疫性 免疫性新生儿溶血免疫性新生儿溶血*机械性损伤机械性损伤 微血管性溶血性贫血微血管性溶血性贫血*生化、物理、化学因素损伤生化、物理、化学因素损伤 疟疾、梭状芽胞杆菌疟疾、梭状芽胞杆菌 感染、高温、砷、铜、蛇毒感染、高温、砷、铜、蛇毒*扣押破坏扣押破坏 脾脏肿大脾脏肿大Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more tim

7、e 除阵发性睡眠性血红蛋白尿症除阵发性睡眠性血红蛋白尿症(PNH)以外，所有红细胞内在缺以外，所有红细胞内在缺陷都是先天性的，而绝大多数红陷都是先天性的，而绝大多数红细胞外溶血因素所致都是后天获细胞外溶血因素所致都是后天获得性的。有些情况是在红细胞内得性的。有些情况是在红细胞内在缺陷的基础上又有外界因素诱在缺陷的基础上又有外界因素诱发溶血。发溶血。（二）先天性和后天获得性（二）先天性和后天获得性Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one mor

8、e time（三）血管内溶血与血管外溶血（三）血管内溶血与血管外溶血教材第176页Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 三、发病情况三、发病情况 溶血性贫血约占同期贫血病人中的溶血性贫血约占同期贫血病人中的1015%其中遗传性溶血病约占其中遗传性溶血病约占55%不同溶血病在不同地区和民族中的发生不同溶血病在不同地区和民族中的发生率不同率不同 Our greatest weakness lies in giving up

9、.The most certain way to succeed is always to try just one more time 广州广州344例溶血性贫血中例溶血性贫血中 异常血红蛋白病异常血红蛋白病 48.3%酶缺乏症酶缺乏症 25.9%自身免疫性溶血性贫血自身免疫性溶血性贫血(AIHA)8.1%阵发性睡眠性血红蛋白尿阵发性睡眠性血红蛋白尿(PNH)7.6%遗传性球形红细胞增多症遗传性球形红细胞增多症(HS)1.2%哈尔滨哈尔滨110例溶血性贫血病人中，例溶血性贫血病人中，PNH 58.2%AIHA 34.6%HS 2.7%Our greatest weakness lies in

10、 giving up.The most certain way to succeed is always to try just one more time（一）实验室诊断（一）实验室诊断：可分为以下两类：可分为以下两类 1、红细胞破坏过多的直接证明：、红细胞破坏过多的直接证明：游离血红蛋白代谢四、溶血的诊断四、溶血的诊断教案第5页（资料）（资料）生化指标检测（教材第（教材第133页）页）Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more t

11、ime 2、红细胞破坏增多的间接证明：、红细胞破坏增多的间接证明：血象、骨髓象教案第5页网织红细胞Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in givin

12、g up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greates

13、t weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just o

14、ne more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed

15、 is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The mos

16、t certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness l

17、ies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time

18、 3、病因诊断思路、病因诊断思路 4、鉴别诊断、鉴别诊断 缺铁性贫血缺铁性贫血 巨幼细胞贫血恢复网织红细胞增高期巨幼细胞贫血恢复网织红细胞增高期 Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 遗传性球形红细胞增多症Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time

19、遗传性椭圆形红细胞增多症Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 微血管病性贫血Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time（一）遗传性球形红细胞增多症（一）遗传性球形红细胞增多症（hereditary spherocytosis HS）HS是一种红细胞膜

20、膜蛋白基因异常所致的遗传性溶血病，多呈常染色体显性遗传（第8号染色体短臂缺失），患者可有不同程度的贫血、黄疸和脾肿大贫血、黄疸和脾肿大，外周血球形红外周血球形红细胞明显增多和红细胞渗透性增加细胞明显增多和红细胞渗透性增加是其主是其主要特征，要特征，脾切除疗效良好。五、红细胞膜缺陷溶血性贫血五、红细胞膜缺陷溶血性贫血Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in givi

21、ng up.The most certain way to succeed is always to try just one more time 2.临床表现临床表现 多成年发病，贫血、黄疸和脾肿大为主要临床表现。青少年生长迟缓并伴有巨脾。感染可加重临床症状。本病患者可并发再障危象，常为短小病毒感染或叶酸缺乏所引起。1.病因及发病机制病因及发病机制 Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 3.检验检验 （1）血象）血象

22、 血片中的红细胞呈球形，直径6.27.0m，细胞大小比较均一，厚度增加2.23.4m，染色后红细胞淡染区消失，染成较深的红色；网织红细胞增加（0.050.20）。（2）骨髓象）骨髓象 红系统增生活跃，有核红细胞高达2560%。Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is alwa

23、ys to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time （3）红细胞渗透脆性试验）红细胞渗透脆性试验 原理：原理：正常红细胞在低渗盐水中膨胀的适应性较大，对低渗盐水有抵抗力，氯化钠浓度为3.84.6g/L时开始溶血，2.83.2g/L时完全溶血。当红细胞膜有缺陷时，红细胞在低渗盐水中的适应性降低，即脆性增加。病人与正常对照相差0.4g/L以上为阳性。遗传性球形红细胞增多症时为阳性

24、，阳性还见于自身免疫性溶血性贫血伴球形红细胞增多。教材136页Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 管号 12345678910 11 1210g/LNaCl(ml)1.71.61.51.41.31.21.11.00.90.80.70.6蒸馏水（ml）0.80.91.01.11.21.31.41.51.61.71.81.9NaCl（g/L）6.86.46.05.65.24.84.44.03.63.22.82.4NaCl

25、（mmol/L）116.3109.4102.695.888.982.175.268.461.654.747.941.0NaCl（%）0.680.640.600.560.520.480.440.400.360.320.280.24Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is alw

26、ays to try just one more time （4 4）自身溶血试验及其纠正试验）自身溶血试验及其纠正试验 离体的红细胞仍能依靠自身能量代谢维持一定的生存时间。正常人红细胞37、48h孵育后，红细胞体积增大，逐渐产生轻度溶血。溶贫时，自身溶血程度明显增强，但加入葡萄糖或三磷酸腺苷（ATP）后，若葡萄糖代谢的酶无缺陷，可获得不同程度的纠正。该试验有助于溶贫的鉴别诊断，但不能作为确诊试验，可作为丙酮酸激酶缺乏症的筛选试验。Our greatest weakness lies in giving up.The most certain way to succeed is always

27、to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time （5 5）酸化甘油溶血试验）酸化甘油溶血试验：膜磷脂被甘油提取，发生溶血，AGLT50150秒。此试验对本病的特异性和敏感性均较高。（6 6）高渗冷溶血试验）高渗冷溶血试验：溶血率增高。（7 7）特殊试验）特殊试验 红细胞膜电泳分析红细胞膜电泳分析：SDS-PAGE电泳（聚丙烯酰胺凝胶电泳）可得到红细胞膜蛋白组分的百分率。红细胞蛋

28、白定量测定红细胞蛋白定量测定：绝大多数HS有一种或多种膜蛋白缺乏，应用放免可直接测定红细胞膜蛋白含量。分子生物学技术应用分子生物学技术应用：目前应用分子生物学技术可检出膜蛋白基因的突变位点。Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 4.诊断诊断（1）脾大、黄疸、贫血脾大、黄疸、贫血为主要临床表现（2）外周血小球形红细胞大于小球形红细胞大于10%（3）骨髓幼红细胞增生骨髓幼红细胞增生（4）红细胞渗透脆性试验增高红细胞渗透脆性

29、试验增高：开始溶血和完全溶血的盐水浓度，超过正常对照的0.8g/L以上（5）48小时自溶试验小时自溶试验；溶血率超过5%，葡萄糖、ATP能部分纠正（6）酸化甘油溶血试验：阳性酸化甘油溶血试验：阳性，AGLT50150秒（7）高渗冷溶血试验：阳性高渗冷溶血试验：阳性本病应与自身免疫性溶贫所致的继发性球形红细胞增多相鉴别。Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time（二）遗传性椭圆形红细胞增多症（二）遗传性椭圆形红细胞增多症 是一

30、组异质性家族遗传性血液病，其特征是外周血中含有大量的椭圆形红细胞25%（正常10%。有溶血的病例其临床表现和实验室检查均与遗传性球形红细胞增多症相似。（三）遗传性口形红细胞增多症（三）遗传性口形红细胞增多症 是一组常染色体显性遗传性溶血病，有家族史，少见。其特征是血片上出现较多的口形红细胞（正常人4%，其中央的淡然区不是圆形而变为狭长的裂缝，类似微张的鱼口。，临床表现与遗传性球形红细胞增多症相似。Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one mo

31、re time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 六、红细胞酶缺陷性溶血性贫血六、红细胞酶缺陷性溶血性贫血 红细胞酶缺乏症是指参与红细胞代谢（主要是糖代谢的酶），由于基因突变导致酶活性或酶性质改变所引起的溶血性疾病。临床上最常见的是红细胞葡萄糖-6-磷酸脱氢酶缺乏症。Our greatest weakness lies in giving up.The most certain way to succeed is

32、always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 细胞葡萄糖-6-磷酸脱氢酶缺乏症 1、概述 2、发病机制Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time （一）红细胞葡萄糖（一）红细胞葡萄糖-6-磷酸

33、脱氢磷酸脱氢酶缺乏症酶缺乏症 1.概述概述 2.发病机制发病机制Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 3.G6PD酶活性分类酶活性分类（1）无诱因的溶血性贫血：（2）蚕豆病或药物性贫血（3）药物性溶血性贫血：（4）酶活性轻度减低或正常的溶血性贫血：Our greatest weakness lies in giving up.The most certain way to succeed is always to tr

34、y just one more time 4.实验室检查实验室检查（1）过筛实验 高铁血红蛋白还原试验：G-6-PD荧光斑点试验：硝基四氮唑兰试验（NBT）纸片法：（2）变性珠蛋白小体（Heinz小体）生成试验：（3）红细胞G-6-PD活性测定：（4）分子生物学法：其中（3）（4）是确诊试验。Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The m

35、ost certain way to succeed is always to try just one more time 八、阵发性睡眠性血红蛋白尿症八、阵发性睡眠性血红蛋白尿症 （一）概述（一）概述 是一种后天获得性造血干细胞基因是一种后天获得性造血干细胞基因突变引起的，是红细胞膜的获得性缺陷突变引起的，是红细胞膜的获得性缺陷引起的对激活补体异常敏感的一种慢性引起的对激活补体异常敏感的一种慢性血管内溶血。临床以与睡眠有关的、间血管内溶血。临床以与睡眠有关的、间歇发作的血红蛋白尿（棕黑色尿）为特歇发作的血红蛋白尿（棕黑色尿）为特征，可伴有全血细胞减少或反复血栓形征，可伴有全血细胞减少或反复

36、血栓形成。成。Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time （二）发病机理（二）发病机理（三）临床表现（三）临床表现 1血红蛋白尿 2不同程度的贫血、感染与出血 3血栓形成Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time （四）实验室检查（四）实验室检查 1血象：

37、血红蛋白低于60g/L 2骨髓象：半数以上患者三系细胞增生活跃，尤以幼红细胞为甚。3溶血检查：血清游离血红蛋白可升高，结合珠蛋白可降低，提示血管内溶血。4尿液：血红蛋白尿发作期有蛋白尿，红细胞阴性但尿隐血试验阳性，患者尿含铁血黄素试验可持续阳性 Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 5特异性血清学试验：（1）酸溶血试验也称Hams试验：特异性高，敏感性略差，是诊断的重要依据。原理：PNH病人的红细胞膜对补体敏感，在酸性

38、条件（PH6.46.5）下，经孵育，能被正常人新鲜血清中的补体溶解。若将正常人新鲜血清灭活，就不能溶解病人的红细胞。该试验是PNH的确诊试验。如骨髓增生不良使补体敏感的红细胞生成减低，或急性溶血发作后补体敏感的红细胞已被溶解，该试验可为阴性。所以，阴性时不能排除PNH。伴有大量球形红细胞的自身免疫性溶血性贫血或遗传性球形红细胞增多症可出现假阳性 Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 酸溶血试验酸溶血试验(Ham)正常人

39、：阴性 临床意义：阳性主要见于PNH。某些自身免疫性溶血性贫血发作严重时可呈阳性Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The

40、most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time （2）蔗糖溶血试验（3）蛇毒因子溶血试验 原理：蛇毒因子（C3b）可通过旁路途径激活补体，PNH患者的红细胞补体系统被激活后，促使PNH补体敏感细胞破坏溶血 Our greatest weakness lies in giving up.The most

41、certain way to succeed is always to try just one more time 九、免疫性溶血性贫血九、免疫性溶血性贫血 根据病因分类：自身免疫性 温抗体型 冷抗体型 异体免疫性 血型不合溶血 新生儿溶血症 药物免疫性 自身抗体型 免疫复合物型 半抗原型 Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 定义定义 AIHA是器官特异性自身免疫性疾病。红细是器官特异性自身免疫性疾病。红细胞作为自

42、身抗原，与相应的自身抗体结合胞作为自身抗原，与相应的自身抗体结合后，在红细胞膜上形成免疫复合物，并激后，在红细胞膜上形成免疫复合物，并激活补体，而杀伤红细胞。活补体，而杀伤红细胞。AIHA是是II型超敏型超敏型自身免疫疾病，又称细胞毒性自身免疫型自身免疫疾病，又称细胞毒性自身免疫疾病。疾病。Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 分类分类根据抗体作用于红细胞膜所需最佳温度根据抗体作用于红细胞膜所需最佳温度1、温抗体型、温

43、抗体型2、冷抗体型、冷抗体型 冷凝集素综合征冷凝集素综合征 阵发性冷性血红蛋白尿阵发性冷性血红蛋白尿Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 实验室检验 血象：为正常细胞性贫血，周围血片可见球形细胞、幼红细胞及

44、少量铁粒幼细胞。偶见红细胞被吞噬现象。网织红细胞增多。骨髓象：幼红细胞增生，偶见红细胞系统轻度巨幼样变。抗人球蛋白试验（Coombs试验）直接试验阳性，温抗体型AIHA主要为抗IgG和抗C3型，偶见有抗IgA型，冷抗体型AIHA几乎均为C3型。间接试验可为阳性或阴性。Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain w

45、ay to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 直接直接Coombs试验试验抗人免疫球蛋白自身抗体Our great

46、est weakness lies in giving up.The most certain way to succeed is always to try just one more time 同种异型抗体抗人免疫球蛋白间接间接Coombs试验试验Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 冷抗体型冷抗体型AIHA有冷凝集素试验阳性或冷热有冷凝集素试验阳性或冷热溶血试验阳性。溶血试验阳性。Our greatest wea

47、kness lies in giving up.The most certain way to succeed is always to try just one more time 七、血红蛋白病七、血红蛋白病血红蛋白病是一组珠蛋白合成缺陷的遗传性贫血性疾病，它是由于生成血红蛋白的珠蛋白肽链（、）的结构异常或合成肽链速率的改变，而引起血红蛋白功能异常所致的疾病。Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our great

48、est weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up.The most certain way to succeed is always to try just

49、 one more time 珠蛋白生成障碍性贫血珠蛋白生成障碍性贫血 1.概述概述 Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time 2珠蛋白生成障碍性贫血珠蛋白生成障碍性贫血 也称地中海贫血，本病是链合成减少，使HbA减少，引起小细胞低色素性贫血，相对过剩的链可与代偿性产生增多的链或链聚合，引起HbF（22）或HbA2（22）增高。而且多余的链可成为不溶性的变性产物，在幼红细胞膜上析出，损害膜和细胞功能，使之在骨髓内破坏、消灭

50、，故虽骨髓内幼红细胞增生很旺盛，但释放至循环血的红细胞不能相应增多，此即无效性造血。Our greatest weakness lies in giving up.The most certain way to succeed is always to try just one more time （1）地中海贫血可分为轻型、重型、中间型。轻型地中海贫血：是地中海贫血基因的杂合子，父母之一患此病。患者可完全无症状，称静止型或微型地中海贫血。重型地中海贫血：是地中海贫血基因的纯合子，父母双方都患轻型地中海贫血。患者多在2岁内发病，逐渐加剧。中间型地中海贫血：多在25岁之间出现贫血，症状介于轻、重