1、Aplastic Anemia (再生障礙性貧血)Wang liHaematology DepartmentThe First Affiliated HospitalReview What is the function of bone marrowHematopoiesisRed blood cells - transport oxygen and nutrientsWhite blood cells - fight infectionplateletshelp blood clotBone marrow haematopoiesis failure, HSC injuredPeripher

2、al blood pancytopeniaTypical symptoms: anemia,infection,bleeding Direct and indirect pathophsiologic pathways causing A.AThe main characters of Aplastic AnemiaGeneral IntroductionClassification SevereModerateAbroadAcuteChronicHomeEpidemiologyIncidence China Annual incidence 7.4 per 100,000 6.01.4Dis

3、tributionEpidemiologyfemalemaleInfant70sChemical factors: drug (anticarcinogen, chloramphenicol, sulfonamide, NSAIDs etc) chemicals (benzene, insecticides etc)Physical factors radiation, X rayBiological factors viruses, severe bacterium, infectionOther pathogenic factorsUnknownEtiology Pathogenesis

4、Failure in hematopoietic stem or progenitor cells Defect in microenvironment of haematopoiesis Immuno-mediated bone marrow failure Genetic aspects: HLA associated susceptibility SeedsSoilHarmful InsectsPresenting symptomsAcute AAChronic AAOnsetacute, short historyslowly onset,longer historyAnemiasev

5、ere, remarkablerelatively moderateBleedingheavy bleeding, multiorganhemorrhage moderate, skin and mucus Infectionmore frequent,moderate, upper respiratory infectionsepsisLaboratory findings Blood count（x109/L） granulocytes 0.5 platelets 20 reticulocytes 15 BM morphologyAcute AAChronic AAmultiplace h

6、ypocellularity lack of megakaryocyteslack of E,G increase in marrow fat increased non-HCSimilar findings, focal area active haematopoiesisBone marrow aspirationNormal BM biopsyThis marrow is taken from a middle aged person, so it is about 50% cellular, with steatocytes admixed with the marrow elemen

7、ts. Normal BM (high power magnification) Note the presence of megakaryocytes, erythroid islands, and granulocytic precursors. This marrow is taken from the posterior iliac crest in a middle aged person, so it is about 50% cellular, with steatocytes admixed with the marrow elements.Aplastic anemia bi

8、opsyHematopoietic elements in this bone marrow biopsy are markedly reduced. Of course, RBC, platelets and granulocytes will often be diminished. Marrow FatAplastic anemia (HP)BM morphology of Acute AARecover phase Diagnostic standard of AA (1987) DiagnosisDiagnosisSignBMPeri BloodexclusionDiagnostic

9、 standard of AA (1987) Decreased peripheral blood count， absolute number of reticulocytes reduced Without megalospleniaDiagnosisBM morphology DiagnosisModerate or severe hypocellularity found at least one aspiration (biopsy) site.Nonhaematopoietic cells increase in BM. Other diseases which may cause

10、 decreased blood count are carefully excluded，such as myelodysplastic syndrome(MDS), acute myelogenous leukemia(AML). Routine therapies for anemia fail to work.DiagnosisMyelodysplastic syndrome -dysmorphic featuresParoxysmal nocturnal haemoglobinuria (PNH)Hypoplastic Acute LeukemiaOthersDifferential

11、 Diagnosis - PancytopeniaAn acquired haematopoietic stem cell defect with predominant haemolytic anaemia.A descriptive term for the clinical manifestation of haemolysis and haemoglobinuria manifest by dark coloured urine in the morning. PNH- Paroxysmal nocturnal haemoglobinuriaParoxysmal nocturnal h

12、aemoglobinuria.Historically test was Hams test; showed red cell lysis by complement activation in acidified serum.Currently test for absent proteins on cell surface. CD55 and CD59TreatmentSupportive CareGrowth HormonesImmune Suppressive TherapyHematopoietic Stem Cell TransplantationRed cell transfus

13、ionPlatelet transfusionManagement of neutropenia private room face mask hand wash broad-spectrum antibiotics if feverSupportive CareIndicated for patients 50 yearsPatients with no HLA matched sibling donorsAnti-Thymocyte Globulin(ATG) or anti-lymphocyte globulin (ALG), cyclosporin, methylprednisoneB

14、est results are for combination therapy.Response is slow, 4-12 weeks to see early improvementImmunosuppressive therapy Response rates 60-70%Relapses are common and continued supportive care needed.Up to 50% of relapsed patients will respond to 2nd course of immunosuppressive therapyAge 55 years.Cond

15、itioning with Cyclophosphamide & antithymocyte globulin, with cyclosporin and methotrexate.Long term overall survival = 80-90%Chronic graft versus host disease (GVHD) remains a problem for 25-40% of patients.HSCT-HLA identical sibling HSCT21 year manPresented with fatigue,pale,tirednessHb 11.0 WBC 2.6,neutrophils 1.1, p