1、Aplastic Anemia (再生障碍性贫血再生障碍性贫血)Wang liHaematology DepartmentThe First Affiliated HospitalReview What is the function of bone marrow 骨髓骨髓Hematopoiesis造血造血Red blood cells-transport oxygen and nutrientsWhite blood cells-fight infectionplateletshelp blood clot 凝结凝结v Bone marrow haematopoiesis failure,H
2、SC 造造血干细胞血干细胞 injuredv Peripheral blood pancytopenia 全血细胞减少全血细胞减少v Typical symptoms:anemia,infection,bleeding v Direct and indirect pathophysiologic pathways causing A.AThe main characters of Aplastic AnemiaGeneral IntroductionClassification SevereModerateAbroadAcuteChronicHomeEpidemiologyIncidence
3、China Annual incidence 7.4 per 100,000 AcuteChronic6.01.4DistributionEpidemiologyfemalemaleInfant70sChemical factors:drug (anticarcinogen 抗癌药抗癌药,chloramphenicol 氯氯霉素霉素,sulfonamide 磺胺磺胺,NSAIDs etc)chemicals (benzene 苯苯,insecticides 杀虫剂杀虫剂 etc)Physical factors radiation,X rayBiological factors viruses
4、,severe bacterium,infectionOther pathogenic factorsUnknownEtiology Pathogenesis Failure in hematopoietic stem or progenitor 祖祖 cells Defect in microenvironment of haematopoiesis Immuno-mediated 免疫介导的免疫介导的 bone marrow failure Genetic aspects:HLA associated susceptibility 敏感敏感SeedsSoilHarmful InsectsP
5、resenting symptomsAcute AAChronic AAOnsetacute,short historyslowly onset,longer historyAnemiasevere,remarkable 显著的显著的relatively moderateBleeding heavy bleeding,Multiorgan 多器官多器官Hemorrhage 出血出血 moderate,skin and mucus Infection more frequent,moderate,upper respiratory infectionSepsis 败血症败血症Laboratory
6、 findings Blood count（x109/L）granulocytes 0.5 platelets 20 reticulocytes 15 BM morphology 骨髓形态学骨髓形态学Acute AAChronic AAmultiplace hypocellularity lack of megakaryocyteslack of E,G increase in marrow fat increased non-HCSimilar findings,focal area active haematopoiesisLaboratory findings Blood count（x
7、109/L）粒细胞粒细胞 0.5 血小板血小板 20 网织红细胞网织红细胞 15 BM morphology 骨髓形态学骨髓形态学Acute AAChronic AA多种细胞减少多种细胞减少巨核细胞缺乏巨核细胞缺乏红细胞、粒细胞缺乏红细胞、粒细胞缺乏 骨髓脂肪增多骨髓脂肪增多非造血细胞增多非造血细胞增多相似表现相似表现,核心核心区域造血活跃区域造血活跃Bone marrow aspiration 吸吸Normal BM biopsyThis marrow is taken from a middle aged person,so it is about 50%cellular,with ste
8、atocytes 平衡细胞（？）平衡细胞（？）admixed 混合混合 with the marrow elements.Normal BM(high power magnification 放大放大)Note the presence of megakaryocytes,erythroid islands,and granulocytic precursors 粒细胞前体细胞粒细胞前体细胞.This marrow is taken from the posterior iliac crest 髂后上嵴髂后上嵴 in a middle aged person,so it is about 50
9、%cellular,with steatocytes admixed with the marrow elements.Aplastic anemia biopsyHematopoietic elements in this bone marrow biopsy are markedly 明显的明显的 reduced.Of course,RBC,platelets and granulocytes will often be diminished 减少的减少的.Marrow FatAplastic anemia(HP)BM morphology of Acute AABM morphology
10、 of Acute AARecover phase Recover phase 恢复恢复阶段阶段Diagnostic standard of AA(1987)DiagnosisDiagnosisSignBMPeri Blood外周血外周血Exclusion排除排除Diagnostic standard of AA(1987)Decreased peripheral blood count，absolute number 绝对数量绝对数量 of reticulocytes reduced Without megalosplenia 脾肿大脾肿大DiagnosisBM morphology Dia
11、gnosisModerate or severe hypocellularity 细胞细胞缺乏缺乏 found at least one aspiration(biopsy)site.Nonhaematopoietic cells 非造血细胞非造血细胞 increase in BM.Other diseases which may cause decreased blood count are carefully excluded，such as myelodysplastic syndrome 骨髓增生异常综合症骨髓增生异常综合症(MDS),acute myelogenous leukemi
12、a 急性骨髓急性骨髓性白血病性白血病(AML).Routine therapies for anemia fail to work.Diagnosis Myelodysplastic syndrome -dysmorphic 异形的异形的 features Paroxysmal nocturnal haemoglobinuria 阵发性睡眠性血红蛋白尿阵发性睡眠性血红蛋白尿(PNH)Hypoplastic Acute Leukemia 低增生性急低增生性急性白血病性白血病 OthersDifferential Diagnosis Pancytopenia全血细胞减少全血细胞减少 An acqu
13、ired haematopoietic stem cell defect with predominant 主要的 haemolytic anaemia 溶血性贫血.A descriptive term 描述词 for the clinical manifestation of haemolysis 溶血 and haemoglobinuria 血红蛋白尿 manifest by dark coloured urine in the morning.PNH-Paroxysmal nocturnal haemoglobinuria Paroxysmal nocturnal haemoglobin
14、uria.Historically 历史上的 test was Hams test;showed red cell lysis 溶解 by complement 补体 activation in acidified 酸化的 serum.Currently test for absent proteins on cell surface.CD55 and CD59TreatmentSupportive CareGrowth HormonesImmune Suppressive TherapyHematopoietic Stem Cell Transplantation Red cell tran
15、sfusion Platelet transfusion Management of neutropenia 中性粒细胞减少 private room face mask hand wash broad-spectrum antibiotics 广谱抗生素 if feverSupportive Care Indicated for patients 50 years Patients with no HLA matched sibling donors 同胞捐助者 Anti-Thymocyte Globulin 抗胸腺细胞球蛋白(ATG)or anti-lymphocyte globulin
16、抗人淋巴细胞球蛋白(ALG),cyclosporin,methylprednisone Best results are for combination therapy.Response is slow,4-12 weeks to see early improvementImmunosuppressive therapy Response rates 60-70%Relapses 复发 are common and continued supportive care needed.Up to 50%of relapsed patients will respond to 2nd course
17、 of immunosuppressive therapy Age 55 years.Conditioning 调节 with Cyclophosphamide 环磷酰胺&antithymocyte globulin 抗胸腺细胞球蛋白,with cyclosporine 环孢菌素 and methotrexate 甲氨蝶呤.Long term overall survival=80-90%Chronic graft versus host disease 慢性移植物抗宿主病(GVHD)remains a problem for 25-40%of patients.HSCT-HLA identi
18、cal sibling HSCT 造血干细胞移植造血干细胞移植 21 year man Presented with fatigue,pale,tiredness Hb 11.0 WBC 2.6,neutrophils 1.1,platelets 45,MCV 104.B12/folate 叶酸/ferritin 铁蛋白 were normal.Main physical examination was unremarkable.Case Presentation Marrow aspirate hypocellular 细胞减少 Marrow biopsy hypocellular Diagnosis?Treatment?Case PresentationThank youJohn Radcliffe Hospital
