APLASTIC

ANAEMIA
Aplastic anemia is pancytopenia with bone marrow
hypocellularity without infiltration or fibrosis
Diagnostic Criteria for Severe aplastic Anaemia

A bone marrow biopsy showing <25% of normal cellularity

or
A bone marrow biopsy showing < 50% of normal cellularity in which <30% of
cells are hematopoietic

AND
Atleast 2 of the following factors :

1.Absolute reticulocyte count < 40,000/mm3

2.Absolute Neutrophil Count < 500/ mm3
3. Absolute Platelet Count <20,000/mm3
Very severe Aplastic Anaemia:

Criteria for severe Aplastic Anaemia should be fulfilled and ANC < 200/mm3
 Etiology:

1. ACQUIRED
1. Idiopathic :
It represent most cases (70-80%) of aplastic anaemia
2. Drugs :

Chloramphenicol
Sulphonamides
Trimethadione
Paramethadione
Chlorpromazine
Chlordiazepoxide
3. Chemical Exposure:

- Inhalation of benzene Vapour for considerable periods, benzene is often

employed as a solvent, often in glue

- Incestisides Chlordane and Chlorophenothane (DDT)

- Trinitrotoluene in Explosive factories

4. Infections:

- Hepatitis virus (Non A, Non –B, Non- C, Non - G)

- Infectious mononucleosis ( Epstein barr Virus)
- Parvovirus B19
5. Immune:
Transfusion-associated graft-versus-host disease (GVHD) that can occur
after infusion of nonirradiated blood products to an immunodeficient
recipient.

Aplastic anemia is strongly associated with the rare collagen vascular

syndrome eosinophilic fasciitis that is characterized by painful
induration of subcutaneous tissues .

Thymoma and hypoimmunoglobulinemia are occasional associations

with aplastic anemia.

Pancytopenia with marrow hypoplasia can also occur in systemic lupus

erythematosus
6. Pregnancy

Aplastic anemia very rarely may occur and recur during pregnancy and
resolve with delivery or with spontaneous or induced abortion

INHERITED/
CONSTITUTIONAL
- Fanconi Anaemia
- Dyskeratosis congenita/ telomer disease
- Shwachman- Diamond syndrome
Fanconi Anaemia ( AR)

Short stature
Absent thump
Absent Radius
Microcephaly
Renal anomalies
Strabismus
Low set ears
Skin pigmentation : Café au lait
It has increased susceptibility to leukemia, myelodysplastic syndrome ,
oral and liver cancers
Dyskeratosis congenita: XR/AR/AD

Nail dystrophy
Leukoplakia

Shwachman –Diamond syndrome : AR

Exocrine pancreatic insufficiency

Bone marrow failure
Cartilage and hair hypoplasia
Short stature
Clinical Features:

Symptoms of Anaemia : Easy fatiguability, weakness, dyspnoea on

exertion

Symptoms of Thrombocytopenia :Bleeding manifestations --

hemorrhage into skin either ecchymosis, petechiae,
epistasix ,menorrhagia, bleeding from gums and elementary canal

Neutropenia result in infection. Chronic skin infection, recurrent chest

infections (pneumonia), ulceration of mouth and pharynx, septicaemia
– frequent cause of death
BLOOD PICTURE

- Anaemia : normocytic normochromic

- Red cell anisocytosis is common and poikilocytosis can occur
- Absolute reticulocyte count : Reduced
- Leukopenia: Particularly neutropenia
- Thrombocytopenia
- Erythrocyte Sedimentation rate : Elevated
A dry tap in which no material at all is obtained
or
A bloody tap in which no material at all is obtained
Treatment
1.Identification and elimination of exposure to causative agent

2. Supportive Care

3.Immunosupportive Therapy

4.Stem cell Transplant

Stem cell transplant:
Patients with severe aplastic anaemia, if they are < 40years old and have a
HLA compactable sibiling, should be transplanted upfront and should not
receive prior immunosuppressive therapy.

It has got 70-80 % chance of long term cure

Most patients do not have a suitable sibling donor. Survival is equivalent

between matched unrelated donors and conventional sibling donors,
although complication rates (mainly graft-versus-host disease and infection)
are higher using unrelated donors.
Transplantation from an HLA haploidentical family donor is increasingly
popular: a donor is almost always quickly available, and post-transplant
cyclophosphamide appears to be effective in preventing graft-versus-host
disease.

Survival is better with donors from same sex:

A male patient with female donor risk of acute graft vs host disease
increased by 33 % compared with male to male transplant patients

A female patient with male donor has increased risk of 20% of graft
rejection
 IMMUNOSUPPRESSION
The standard regimen of antithymocyte globulin (ATG) in combination with cyclosporine
The success rate is between 60 -70% when used in combination.

Horse Anti thymocyte globulin : 20 – 40mg/kg for 4 days Daily infusion over 6-8 hours
Rabbit Anti thymocyte globulin : 3.75 mg/kg for 5 days

ATG can cause serum sickness in 40 % cases in the 2 nd and 3rd week following ATG.
Serum sickness, a flulike illness with a characteristic cutaneous eruption and arthralgia,
All patients should receive steroid to prevent serum sickness

Cyclosporin
Cyclosporine is administered orally at an initial high dose, with subsequent adjustment according to blood levels.
Its most important side effects are nephrotoxicity, hypertension, and seizures.
Oral Cyclosporin at 5 ug/kg/day . It is continued for 6 months with slow tapering after that
Androgens:

Controlled trials have not shown efficacy, but androgen continues to be

useful in some patients with non-severe aplastic anaemia.

Androgen increases telomere by indirect upregulation of human

telomerase reverse transcriptase (hTERT) promoter leading to response
in patients with short telomer
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