Presentation on theme: "Anemia due to impaired hematopoietic function of bone maarrow"— Presentation transcript:
1Anemia due to impaired hematopoietic function of bone maarrow Wu Chunmei
2Aplastic anemia Pure red cell aplasis Apastic crisis Anemia due to impaired hematopoietic function of bone maarrowA group of clinical syndromes results in a reduction in one, two or all three cell lines(red cells，neutrophils and platelets) in peripheral blood and aplasia in bone marrow which caused by disturbance in HSC proliferation and differatiation and/or destruction of hematopoietic microenviroment.Aplastic anemiaPure red cell aplasisApastic crisis
3Aplastic AnemiaDefinitionAplastic anemia is a group of disorders characterized by a failure of bone marrow hematopoietic function that results in varying degrees of pancytopenia with a marked bone marrow hypocellularity.
4Classification and Etiology: Aplastic Anemia (AA)-Congenital : (Fanconi anemia)-Acquired IdiopathicSecondary toAR inheritanceDrugsa and chemicals,BiologicalPhysicalEndocrine agents>90%
8Fanconi anemia is an autosomal recessive inherited condition that is associated with abnormal skin pigmentation, short stature, abnormal radii and thumbs, renal abnomalies, microcephaly, and an elfin-like appearance.
11Mechanism of AA 1. defects in HSC (seed) 2. failure of the stromal microenvironment of marrow (soil) and impaired production or release of hematopoietic growth factors.(huafei)3. cellular or humoral immune suppression of the marrow. （worm）4. Genetic events : predisposition HLA-II DR2, DPw3combination
12induced factors (secondary） Genetic eventsimmune suppressionmicroenvironment and growth factorsHSCHSC pool decreaseFail to proliferate and matureDifferent PrecursorsG,E,P productionanemiainfectionbleedingpancytopenia
13Clinical features of AA 1.varying degrees of anemia (more severe)2.hemorrhage ( bruising, petechiae, bleeding gum, cerebral or retinal hemorrhage)3.infection (fever, chill, sore throat, ulceration of mouth and paryngitis)4. Without hepatosplenomegaly or lymphadenopathy
14Clinical types and Characteristics Acute aplastic anemia(AAA)(SAA-I)AAA: acute episodes and developing rapidly, leading to death. The degree of anemia is getting worse with extensive bleeding, infection, etc. that called severe AA-I.Chronic aplastic anemia(CAA)Acute episode(SAA-II)CAA: The onset may be insidious, with a gradual fall in red cells leading to pallor,weakness, and fatigue，bleeding and infection not often occur or slightly.
17Laboratory features Blood: -- varying degrees of pancytopenia(RBC,WBC, BPC )--an absolute low of reticulocyte ( PNH：ret. increased)--normocytic or with macrocytosis (due to high level of EPO, or abnormal clone, such as MDS and PNH)-- absolute neutrophil count low(suggest prognostic--less than 500/ul ,or 200/ul)--relative lymphocytosis
21Bone marrow:The marrow aspirate typically contains numerous spicules with empty fatty spaces and relatively few hemopoietic cells.Mass of non-hemopoietic cells (lymphocytes, plasma cells, macrophages, and mast cells) may be prominent, but this probably reflects a lack of other cells rather than an increase in these elements.
22Typical figure--most often hypocellular(some are cellular or even hypercellular, but megakaryocytes usually reduced.)--dyserythropoiesis (or mild or megaloblastoid features )--dysgranulocytopoiesis(or normal)--absent or rare megakaryocytes--Increase of intracellular and extracellular iron
31Marrow biopsy: --hypocellular marrow --increased fat cells --absence of myelofibrosisSAA has been defined as a marrow of less than 25 percent cellularity or less than 50% cellularity with less than 30% hemopoietic cell, with at least two of the following:neutrophil count less than 0.5×109/l;platelets less than 20×109/l;anemia with a corrected reticular index of less than 1% or less than 15×109/l.
32Other tests: Ham test APL Tc subtypes in peripheral blood (Ti/Th ) EPO FEPHematopoietic stem cell culture
33Hematopoietic stem cell culture for: diagnosis ; study of mechanism ; guide therapy;observation of effective therapy;assessment to diseaseCFU-GM BFU-E CFU-E CFU-MG
34Cause patient’s marrow Lc serum Therapy Mechanism GM-CFUCause patient’s marrow Lc serum TherapyN marrow N marrowStem cell normal normal BMTimmune Tc normalSuppression serum normalME normal normal normalImmune suppressive agents
35Diagnostic criterion of AA Pancytopenia, low reticulocyteabsence of hepatosplenomegalymass of non-hematopoietic cells in marrow granules and hypoplastic marrow from one or more aspirating site(if cellularity, mainly late normoblasts, and megakaryocytes )4. Exclude the following disordersPNH, MDS, Mf, AL5. The common drugs for anemia without effect
36Differential diagnosis With pancytopenia and hypoplastic marrow 1.hypoplastic myelodysplastic syndrome(MDS)2.PNH(Ham ,sucrose test or CD59)3.hypoplastic acute lymphocytic leukemia4.hairy cell leukemiaImmunophenotyping using flow cytometryTartrate-resistance acid phosphatase
38Relationship of AA and PNH: AA-PNH syndromeAA crisisPNHAATypicalatypicalClinical features of AAHam test positive or Hburia,Rous test positive
39Aplastic crisisAcute temporary failure of hepatopoietic function in bone marrow caused by infection, tumor, hemolytic disorders and other events, called aplastic crisis. It is self-limited and recovery when the induced events disappear.
40Pure red cell aplastic anemia () Pure red cell aplasia is caused by a selective destruction or inhibition of erythroid progenitor cells. It is characterized by an anemia and reticulocytopenia and occurs as an acute or chronic condition.Aplastic crisisAcute PRCA: transient disorderChronic PRCA: constitutionalacquired-- autoimmune disorderthymic tumor
41QuestionsHow to differentiate acute AA and chronic AA.PRCAWhat is acute arrest of hemopoiesis or acute aplastic crisis?(temporary, selflimiting , secondary and induced )Non-hematopoietic cells
42Secondary anemiaMYELOPATHIC ANEMIASThese anemias are due to the bone marrow infiltration or replacement by abnormal tissues such as malignant metastases, myelosclerosis, leukemia and myeloma.
43Pathogenesis of myelopathic anemia: --bone marrow damage--hemorrhage--hemolysis
44Clinical Features--severe anemia--bleeding problems may occur--splenomegaly and hepatomegaly is common--symptoms referable to underlying disease
45Lab FindingsBlood--varying degrees of anemia (most normocytic; slightly macrocytic)--distinct anisocytosis and poikilocytosis--leukoerythroblastic anemia:--reticulocytosis and polychromatophilia--The WBC count may be variable--The platelet count is often low, giant, bizarre shaped with abnormal function.
46What is leukoerythroblastic anemia? The patients suffering from anemias with nucleated RBCs and immature granulocytes in the peripheral blood.disruption of marrow sinusoidshematopoiesis in extramedullary sitesWhy?
47.Bone marrow--The marrow aspiration may fail or show metastatic cells and so on.--The marrow biopsy is necessary to establish the diagnosis.Other tests:--x-ray--NAP--CD