1. Anemia due to impaired hematopoietic function of bone maarrow
Wu Chunmei

2. Aplastic anemia Pure red cell aplasis Apastic crisis
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

3. Aplastic Anemia
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.

4. Classification and Etiology:
Aplastic Anemia (AA)
-Congenital : (Fanconi anemia)
-Acquired Idiopathic
Secondary to
AR inheritance
Drugsa and chemicals,
Biological
Physical
Endocrine agents
>90%

8. 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.

11. Mechanism 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, DPw3
combination

12. induced factors (secondary）
Genetic events
immune suppression
microenvironment and growth factors
HSC
HSC pool decrease
Fail to proliferate and mature
Different Precursors
G,E,P production
anemia
infection
bleeding
pancytopenia

13. 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

14. Clinical 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.

17. 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

18. Reticularcyte decrease

19. CAA blood film

20. AAA blood film

21. 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.

22. Typical 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

24. AAA blood film

25. CAA bone marrow

26. CAA bone marrow

27. CAA bone marrow

31. 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 0.5×109/l;
platelets less than 20×109/l;
anemia with a corrected reticular index of less than 1% or less than 15×109/l.

32. Other tests: Ham test APL Tc subtypes in peripheral blood (Ti/Th ) EPO
FEP
Hematopoietic stem cell culture

33. 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

34. Cause patient’s marrow Lc serum Therapy
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

35. Diagnostic criterion of AA
Pancytopenia, low reticulocyte
absence of hepatosplenomegaly
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

36. 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

38. Relationship of AA and PNH:
AA-PNH syndrome
AA crisis
PNH AA
Typical
atypical
Clinical features of AA
Ham test positive or Hburia,Rous test positive

39. Aplastic crisis
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.

40. 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.
Aplastic crisis
Acute PRCA: transient disorder
Chronic PRCA: constitutional
acquired-- autoimmune disorder
thymic tumor

41. Questions
How to differentiate acute AA and chronic AA.
PRCA
What is acute arrest of hemopoiesis or acute aplastic crisis?(temporary, selflimiting , secondary and induced )
Non-hematopoietic cells

42. Secondary anemia
MYELOPATHIC ANEMIAS
These anemias are due to the bone marrow infiltration or replacement by abnormal tissues such as malignant metastases, myelosclerosis, leukemia and myeloma.

43. Pathogenesis of myelopathic anemia:
--bone marrow damage
--hemorrhage
--hemolysis

44. Clinical Features
--severe anemia
--bleeding problems may occur
--splenomegaly and hepatomegaly is common
--symptoms referable to underlying disease

45. Lab Findings
Blood
--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.

46. 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 sites
Why?

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