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) -Acquired Idiopathic Secondary to Drugsa and chemicals,

BiologicalPhysicalEndocrine 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

anemiainfectionbleeding

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

Reticularcyte decrease

CAA blood film

AAA blood film

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

AAA blood film

CAA bone marrow

CAA bone marrow

CAA bone marrow

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.

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, AL5. 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 cytometryTartrate-resistance a

cid phosphatase

Relationship of AA and PNH:

AA-PNH syndrome

PNHAA

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:--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 sitesWhy?

.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