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Aplastic Anemia

It is characterized by peripheral blood pancytopenia in association with bone marrow hypocellularity involving granulocytic, erythroid and megakaryocytic cell lines. 
Etiology of Aplastic Anemia
  1. Idiopathic (more than 50%)
  2. Drug – induced (dose dependent, idiosyncratic) Anticancer drugs
    1. Antimicrobials (chloramphenicol, sulfonamides, penicillins)
    2. Anticonvulsants (phenytoin, ethosuximide, carbamazepine)
    3. Antithyroid agents (carbimazole, propylthiouracil)
    4. Antidiabetic agents (tolbutamide, chlorpropamide)
    5. Miscellaneous (gold compounds, D – penicillamine, bismuth, ticlopidine, thiocyanates, acetazolamide).
  3. Chemical or toxin (benzene, carbon tetrachloride, insecticides)
  4. Radiation
  5. Infection (Non A, Non B, Non C hepatitis, EBV, parvovirus, tuberculosis, HIV)
    (Ref. Hari. 18th ed., Table 171-1)
  6. Pregnancy (remits following delivery in some)
  7. Thymoma (usually associated with pure red cell aplasia)
  8. Paroxysmal nocturnal hemoglobinuria (PNH develops in 5 – 10% of patients with aplastic anemia and 25% of patients with PNH develop aplastic anemia)
  9. Constitutional (Fanconi’s anemia, familial aplastic anemia, dyskeratosis congenita)
  10. Associated with myelodysplasia (patients with aplastic anemia may develop a myelodysplastic syndrome later).
  11. Pernicious anemia

Note: Hepatitis A is not a cause of Aplastic anemia.


Fanconi's anemia is a congenital disorder responsible for a form of aplastic anemia. It is a cause of normocytic normochromic anemia. 

Causes of Aplastic Anemia

    1. Drugs: antimetabolites, antimitotic agents, chloramphenicol, phenylbutazone, sulfonamides
    2. Radiation
    3. Chemicals: benzene, solvents, insecticides
    4. Viruses: non-A, non-B, non-C hepatitis, Epstein-Barr virus
    5. Paroxysmal nocturnal hemoglobinuria
    6. Miscellaneous: pregnancy, connective tissue disorders
    1. a. Fanconi anemia
    2. Dyskeratosis congenita
    3. Schwachman syndrome

Differential diagnosis of Pancytopenia

Pancytopenia with hypocellular bone marrow

Hypocellular bone marrow ± cytopenia

  1. Acquired aplastic anemia
  2. Constitutional aplastic anemia (Fanconi's anemia, dyskeratosis congenita)
  3. Some myelodysplasia syndromes
  4. Aleukemic leukemia (AML)
  5. Some lymphomas of bone marrow
  1. Q fever
  2. Legionnaires' disease
  3. Anorexia nervosa, starvation
  4. Mycobacteria

Pancytopenia with cellular bone marrow

Primary bone marrow diseases

Secondary to systemic diseases

  1. Myelodysplasia syndromes
  2. PNH
  3. Some aleukemic leukemia
  4. Myelophthisis
  5. Bone marrow lymphoma
  6. Hairy cell leukemia
  7. Myelofibrosis
  1. SLE, Hypersplenism
  2. B12, folate deficiency
  3. Overwhelming infection
  4. Chronic Alcoholism
  5. Brucellosis
  6. Sarcoidosis
  7. Tuberculosis
  8. Leishmaniasis


Criteria for Severe Aplastic Anemia: (Any two blood criteria and either one-marrow criterion).
  1. Blood
    1. Neutrophils < 500/μl           
    2. Platelets  < 20,000/μl            
    3. Reticulocytes < 1%
  2. Bone marrow
    1. Severe hypocellularity  
    2. Moderate hypocellularity with < 30% of residual cells being hematopoietic
Clinical Features
  1. Hb: Fatigue
  2. TLC: infection, fever
  3. Platelet: bleeding

Extra Edge: Splenomegaly & Reticulocytosis are never a feature of primary aplastic anemia (AIPG 07)

Treatment of Aplastic Anemia

Mild aplastic anemia
  1. Antibiotic therapy: Fever of any sign of infection is an indication for empiric broad – spectrum antibiotic therapy.
  2. Hematopoietic growth factors like GM – CSF, G – CSF, erythropoietin are given.
    1. Supportive care          
    2. RBC transfusions as necessary             
    3. Platelet transfusions as necessary
Severe aplastic anemia
  1. Neutrophil count <500/ml                
  2. Platelet count <20,000/ml   
  3. Reticulocytes <1%                   
  4. BM cellularity <2%

Fanconi Anemia (FA)

  1. It is a genetic disease that affects children and adults.
  2. Autosomal recessive
  3. Because of the failure of hematologic components to develop - leukocytes, red blood cells and platelets
Many patients eventually develop AML. Older patients are extremely likely to develop head and neck, esophageal, gastrointestinal, vulvar and anal cancers.
Hematological abnormalities
  1. Symptoms appear progressively and often lead to complete bone marrow (BM) failure.
  2. While at birth blood count is usually normal, macrocytosis /non-megaloblastic anemia, is the first detected abnormality,
  3. Within the next 10 years, over 50% of patients presenting hematological abnormalities will have developed pancytopenia,
  4. The deficiencies cause increase risk of hemorrhage and recurrent infections, respectively.
  1. The first line of therapy is hematopoietic stem cell transplantation.
  2. Approximately 50-75% of patients respond to androgens, which are used when transplantation is not an option.

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