Aplastic anemia (AA) is a disease characterized by pancytopenia and hypocellular (or fatty) marrow. It is a rather rare disorder, with an annual incidence of about 2-6 per million population. In about 50% of these cases, the etiology is unknown ( Idiopathic Aplastic Anemia ). The second leading cause of AA is drug and chemical use. Based upon the severity of disease, AA can be considered as a severe or moderate disease.

Severe AA is characterized by any two of the following blood criteria along with the presence of either marrow criteria :

Blood criteria :
Neutrophils < 500/mm3,
Platelets <20,000/mm3,
Corrected reticulocytes <1%.

Marrow criteria :
Severe hypocellularity (<25%)
Moderate cellularity (<50%) with less than 30% of hematopoietic cells.

Moderate AA is defined as the failure to meet criteria for severe disease but with at least two of three blood counts decreased.
Platelets <40,000/mm3
Neutrophils < 1,500/mm3 with hypocellular marrow biopsy.

If left untreated, 80-90% of patients with severe AA will die within a year. These patients die from infections (immunocompromised patients) or bleeding. The prognosis for patients with moderate AA is considerably better, although many patients will die of complications of pancytopenia or transfusion-related hemosiderosis. Prognostic systems have been developed and, in general, may be used to try to individualize treatment in particular patients.

Overall, age and level of granulocytopenia are the two most important prognostic determinants.

Table 1 : Causes of Pancytopenia in Childhood

• Artefact: clot in sample
  
  
• Genuine (by dominant mechanism)
  
  
  • Destruction of mature elements
    
    
    • Infection, most commonly viral
    • Immune mediated
      
      • Infection
      • SLE
      • Complement - PNH
        
        
  • Marrow failure (stem cells, mature elements)
    
    
  • Infiltration
    
    • Leukemia
    • Other malignancies
    • Panhypoplasia
    • Myelosclerosis
    • Osteopetrosis
      
      
• Severe megaloblastosis
  
  • Sequestration
  • Hypersplenism (most common cause portal hypertension)
  • Mechanism obscure
    
    
• Organic acidemias
  
  

Blood picture in Aplastic anemia

Pancytopenia is usually severe (Hb to about 3 g/dl). In about 40% of cases, erythrocytes are macrocytic. Reticulocytes are usually decreased, but occasionally are inexplicably excessive for the anemia. HbF may be increased, especially in genetic types and those with macrocytosis, to about 15% of the total, with heterogenous distribution.

As a result of diminution in the erythron, serum iron and transferrin saturation are increased; B12 and folate may be increased. Erythrocyte i (and in some cases) I antigen may be increased. Lymphocytes are normal to decreased. Platelet size is not increased (cf immune thrombocytopenias)

The first sign of recovery is a rise in reticulocyte count, followed by increase in Hb, then neutrophils, with platelets slowest to recover; if at all.

Marrow picture in Aplastic anemia

Hypoplasia may be patchy, especially early in the disease. Marrow consists of little more fat, stromal cells, lymphocytes and plasma cells; mast cells may be prominent. Because of diminution in the erythron, storage iron and sideroblasts may be increased; ring sideroblasts are not seen, except in rare specific syndromes e.g. Pearson's.