大四下内科202血液052aplastic anemia li wang

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 marrowHematopoiesisRed blood cells - transport oxygen and nutrientsWhite blood cells - fight infectionplateletshelp blood clotv Bone marrow haematopoiesis failure, HSC injure

2、dv Peripheral blood pancytopeniav Typical symptoms: anemia,infection,bleeding v Direct and indirect pathophsiologic pathways causing A.AThe main characters of Aplastic AnemiaGeneral IntroductionClassification SevereModerateAbroadAcuteChronicHomeEpidemiologyIncidence China Annual incidence 7.4 per 10

3、0,000 6.01.4DistributionEpidemiologyfemalemaleInfant70sChemical factors: drug (anticarcinogen, chloramphenicol, sulfonamide, NSAIDs etc) chemicals (benzene, insecticides etc)Physical factors radiation, X rayBiological factors viruses, severe bacterium, infectionOther pathogenic factorsUnknownEtiolog

4、y Pathogenesis 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 h

5、istoryAnemiasevere, remarkablerelatively moderateBleeding heavy bleeding, multiorganhemorrhage moderate, skin and mucus Infection more frequent,moderate, upper respiratory infectionsepsisLaboratory findings Blood count（x109/L） granulocytes 0.5 platelets 20 reticulocytes 15 BM morphologyAcute AAChron

6、ic AAmultiplace hypocellularity 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

7、the marrow elements. 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.A

8、plastic anemia biopsyHematopoietic 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 AABM morphology of Acute AARecover phase Recover phase Diagnostic standard of AA (198

9、7) DiagnosisDiagnosisSignBMPeri BloodexclusionDiagnostic 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.Nonhaematopoie

10、tic cells increase in BM. Other diseases which may cause decreased blood count are carefully excluded，such as myelodysplastic syndrome(MDS), acute myelogenous leukemia(AML). Routine therapies for anemia fail to work.Diagnosis Myelodysplastic syndrome -dysmorphic features Paroxysmal nocturnal haemogl

11、obinuria (PNH) Hypoplastic Acute Leukemia OthersDifferential Diagnosis - Pancytopenia An 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. P

12、NH- Paroxysmal nocturnal haemoglobinuria Paroxysmal nocturnal haemoglobinuria. 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 Suppressiv

13、e TherapyHematopoietic Stem Cell Transplantation Red cell transfusion Platelet transfusion Management of neutropenia private room face mask hand wash broad-spectrum antibiotics if feverSupportive Care Indicated for patients 50 years Patients with no HLA matched sibling donors Anti-Thymocyte Globulin

14、(ATG) or anti-lymphocyte globulin (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 are common and continued supportive care needed. Up to 50% of relapsed patien

15、ts will respond to 2nd course of immunosuppressive therapy Age 55 years. Conditioning 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 HSCT 21 year man Presented with fatigue,pale,tiredness Hb 11.0 WBC 2.6,neutrophils 1.1, p