Presentation on theme: "Anemia due to impaired hematopoietic function of bone maarrow Wu Chunmei."— Presentation transcript:
Anemia due to impaired hematopoietic function of bone maarrow Wu Chunmei
Anemia due to impaired hematopoietic function of bone maarrow A 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 anemia Pure red cell aplasis Apastic crisis
Definition Aplastic 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. Aplastic Anemia
Classification and Etiology: Aplastic Anemia (AA) -Congenital : (Fanconi anemia)Fanconi anemia -Acquired Idiopathic Secondary to Drugsa and chemicalsDrugsa and chemicals, Biological Physical Endocrine agents >90% AR inheritance
Fanconi 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.
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, DPw3 Mechanism of AA combination
induced factors (secondary ） microenvironment and growth factors HSC HSC pool decrease Fail to proliferate and mature Different Precursors G,E,P production pancytopenia anemia infection bleeding Genetic events immune suppression
Clinical 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
Clinical types and Characteristics Chronic aplastic anemia(CAA) (SAA-II) Acute aplastic anemia(AAA) (SAA-I) Acute episode 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. 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.
Laboratory 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
Bone 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.
--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 Typical figure
Marrow biopsy: --hypocellular marrow --increased fat cells --absence of myelofibrosis SAA 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 0.5×10 9 /l; platelets less than 20×10 9 /l; anemia with a corrected reticular index of less than 1% or less than 15×10 9 /l.
Other tests: Ham test APL Tc subtypes in peripheral blood (Ti/Th ) EPO FEP Hematopoietic stem cell culture
Hematopoietic stem cell culture for: diagnosis ; study of mechanism ; guide therapy; observation of effective therapy; assessment to disease CFU-GM BFU-E CFU-E CFU-MG
Mechanism GM-CFU Cause patient’s marrow Lc serum Therapy N marrow N marrow Stem cell normal normal BMT immune Tc normal Suppression serum normal ME normal normal normal Immune suppressive agents
Diagnostic criterion of AA 1.Pancytopenia, low reticulocyte 2.absence of hepatosplenomegaly 3.mass 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 disorders PNH, MDS, Mf, AL 5. The common drugs for anemia without effect
Differential diagnosis With pancytopenia and hypoplastic marrow 1.hypoplastic myelodysplastic syndrome(MDS) 2.PNH(Ham,sucrose test or CD59) 3.hypoplastic acute lymphocytic leukemia 4.hairy cell leukemia Immunophenotyping using flow cytometry Tartrate-resistance acid phosphatase
Relationship of AA and PNH: AA-PNH syndrome PNH AA Typical atypical AA crisis Clinical features of AA Ham test positive or Hburia,Rous test positive
Acute 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. Aplastic crisis
Pure 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. Acute PRCA: transient disorder Chronic PRCA: constitutional acquired-- autoimmune disorder thymic tumor Aplastic crisis
Questions 1.How to differentiate acute AA and chronic AA. 2.PRCA 3.What is acute arrest of hemopoiesis or acute aplastic crisis?(temporary, selflimiting, secondary and induced ) 4.Non-hematopoietic cells
MYELOPATHIC ANEMIAS These anemias are due to the bone marrow infiltration or replacement by abnormal tissues such as malignant metastases, myelosclerosis, leukemia and myeloma. Secondary anemia
Pathogenesis of myelopathic anemia: --bone marrow damage --hemorrhage --hemolysis
Clinical Features --severe anemia --bleeding problems may occur --splenomegaly and hepatomegaly is common --symptoms referable to underlying disease
Lab Findings Blood --varying degrees of anemia (most normocytic; slightly macrocytic) --distinct anisocytosis and poikilocytosis --leukoerythroblastic anemia:leukoerythroblastic anemia: --reticulocytosis and polychromatophilia --The WBC count may be variable --The platelet count is often low, giant, bizarre shaped with abnormal function.
What is leukoerythroblastic anemia? The patients suffering from anemias with nucleated RBCs and immature granulocytes in the peripheral blood. disruption of marrow sinusoids hematopoiesis in extramedullary sitesextramedullary sites Why?
.Bone marrow --The marrow aspiration may fail or show metastatic cells and so on. metastatic cells --The marrow biopsy is necessary to establish the diagnosis. Other tests: --x-ray --NAP --CD