Just like a normal and aplastic marrow

In AA there must be at least two of the following:

(i)Haemoglobin below 10 gm/dL

(ii) Platelet count below 50× 10 ⁹ /L

(iii)Neutrophil count below 1.5×10 ⁹ /L

• BM cellularity <25%, or 25–50% with <30% residual haemopoietic cells 2 out of 3 of the following:
• 1. Neutrophils <0.5 × 10⁹ /L
• 2. Platelets < 20 × 10⁹ /L
• 3. Reticulocytes < 60 × 10⁹ /L

Severe AA

• As for severe AA but neutrophils <0.2 × 10⁹ /L.

Very severe AA

• Patients not fulfilling the criteria for severe or very severe aplastic anaemia.

Non-severe AA

AETIOLOGY

1.ACQUIRED

2.INHERITED

Idiopathic

Inevitable

Idiosyncratic

Infections

Immune mediated

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Some conditions associated with AA

1. PNH

2. Pregnancy – related.

3. Use of agricultural pesticides such as organophosphates, lindane, DDT ,carbamates etc.

4. Benzene exposure, hair dyes, glycol ethers, cutting oils and lubricating agents

1. Fanconi anemia(FA),

2. Dyskeratosis congenita (DC),

3. Swachman diamond syndrome (SDS).

Hemopoietic stem cells

(HSC; the seed)

Cells of micro

environment (the soil)

Normal hematopoiesis depends on a complex interaction of several cell types

Is AA a disease of seed or soil?

The difficulty is deciding

(1)which

comes first and

(2) whether there is a causal relationship between the two

• Both quantitative and qualitative defect in the haemopoietic stem cell compartment.

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• The bone marrow microenvironment functions normally in most patients.

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• AA is not due to deficiency of any known haemopoietic growth factor (HGF).

Haemopoietic defect in AA

The immune-mediated nature of acquired AA

Short telomeres

About 10–15% of patients with AA have shortened telomeres

The consequences are genomic instability, defects in DNA repair resulting in increased risk of malignant transformation (MDS, AML), bone marrow failure.

INVESTIGATION

• Pancytopenia with reticulocytopenia
• Raised MCV common.

CBC

• Anisopoikilocytosis, macrocytosis
• Toxic granulation of neutrophils may be found.
• Thrombocytopenia

Blood film examination

• Hypocellular fragments and trails. Reduced/absence of haemopoietic lineages
• Dyserythropiesis common. Absence of dysplasia in granulocytic and megakaryocytic lineages.
• Iron stain to exclude ringed sideroblasts

Aspiration

• Hypocellular. Absence of blasts. Lymphoid aggregates (reactive) common. Reticulin stain negative.
• CD34 immunocytochemistry negative.

Trephine

Liver function tests,

Vitamin B12

and folate assay

• HBs Ag
• Anti HCV
• Anti HIV…..etc

Viral marker

• SLE .

Antinuclear antibody and Anti dsDNA

• Chest X-ray
• HRCT of chest, neck
• Abdominal ultrasound or CT scan:

Radiology

Tests to detect an associated abnormal clone

PNH clone

• PNH clone detected in up to 40% of AA patients.

Tests to exclude an inherited bone marrow failure syndrome

DEB test

Peripheral blood telomere length

Emerging diagnostic tests

PB MDS gene mutation panel

Single nucleotide polymorphism

(SNP)-array karyotyping

Exome/whole

genome sequencing

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• Later evolution to MDS/AML
• Worse response and survival following IST

ASXL1,DNMT3A

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• Confer good prognosis

BCOR,

BCORL1 and PIG-A genes

Detection of somatic mutations in AA

DIFFERENTIAL DIAGNOSIS

• Dysplastic neutrophils, BM dysgranulopoiesis and dysmegakayopoiesis, Ringed sideroblasts
• Blasts in PB or BM,

1. Hypocellular MDS

2. Hypocellular AML

3. Hypocellular ALL in children

• Examine trephine carefully for foci of lymphoma and perform immunophenotyping and gene rearrangement analyses.

4. Hodgkin

5.Non-Hodgkin

lymphoma

SUPPORTIVE

TREATMENT

DEFINITIVE

TREATMENT

Transfusions

Iron chelation therapy

Control of Infections

Immunosuppressive therapy

The standard regimen for IST comprises the combination of horse ATG and CsA

Cyclophosphamide

Alemtuzumab

Eltrombopag

Androgens

Some drugs used in AA

MSD

UCB

MUD