Acquired Aplastic Anemia

What is Acquired Aplastic Anemia

Often caused by various external insults. Incidences like western countries have 2-6 cases/million population/year. In Asia, there are a higher number of incidents. In Japan it was noticed up to 14-15 cases/million population/year. Mechanism implicated:

• Direct injury to HSCs
• Immune mechanism
• Abnormal BM environment which disfavours hematopoiesis.

Etiology

• In children, many cases are Idiopathic
• Radiation can be a significant cause
• Drugs can also have a role in it
• Viruses: CMV, EBV, HBV, HCV HIV (Rare)
• Pregnancy
• Immune diseases: Thymoma, Eosinophilic Fasciitis, Hypogammaglobulinemia
• PNH
• Marrow replacement: Leukemia, MDS, Myelofibrosis
• Nutritional deficiency: Vitamin B12, Folic Acid (Rarely)
• Autoimmune
• Cryptic dyskeratosis congenita (no physical stigmata)
• Telomerase reverse transcriptase haploinsufficiency

Dose-dependent toxicity

• Antimetabolites and alkylkating agents.
• Cytotoxic antibiotics
• Etoposide, vinblastine, paclitaxel
• Colchicine, insecticides, benzene

Dose-independent/idiosyncratic

• Antibiotics (Methicillin, Tetracyclin and Chloramphenicol)
• NSAIDs, Gold
• Antiepileptic Agents: Valproate, Ethosuximide, CBZ
• Quinidine
• Diuretics
• Chlorpropamide, Tolbutamide
• Anti-thyroid drugs
• Antihypertensives: ACEIs, Methyldopa (Rare)

Clinical findings in  Acquired Aplastic Anemia

• Anemia, Fatigue, exercise intolerance
• Recurrent infection
• Bleeding manifestation
• May and may not be history of preceding insult.

Laboratory findings

• ↓ HCT
• ↓ Reticulocyte count
• ↓ TLC, ↓ ANC
• ↓ Platelet count
• BM: Cellularity (<30%) especially in severe, symptomatic cases
• Flow cytometry
  • CD55
  • CD59
• Macrocytic or Normocytic - Normochromic picture of RBCs.

Categories of Aplastic Anemia

• Essential: BM Cellularity <30% on biopsy
• Moderate AA- When ≥2 of the following are present
  • ANC: 500-1500/mm³
  • Platelets: 20000 to 1 Lakh/mm³
  • Reticulocyte Count < 1% after correction for Hematocrit
• Severe AA: When ≥2 of the following are present
  • ANC: <500/ mm³
  • Platelets: <20000/mm³
  • Reticulocyte Count <1% after correction for Hematocrit

Complications in Aplastic Anemia

• Severe Anemia: CCF
• Recurrent infection: Bacterial/ Viral/ fungal
• Life threatening hemorrhage

Progression to malignancy

Rarely acquired AA as compared to IBMFSs. But can happen, especially if G-CSF used > 7 days.

Treatment

• Moderate AA: Supportive care + observation with close follow up. 65% of moderate cases progress to severe forms.10-15% remain the same and remaining show spontaneous remission where drug induced effects tend to improve with time. Severe Aplastic Anemia
  • Allogenic BM/ HSCT when HLA-matched sibling donor is available (20-25%) - is the therapy of choice
  • Preparative regimen incorporates cyclophosphamide, Fludarabine and ATG
• Alternative for preparation and conditioning is Alemtuzumab
• Risks pertaining to BMT are the usual ones
• If Donor N/A in Severe AA- Use Immunosuppressants. Cyclosporine + ATG: Response rate of 70-80% in 6 months. In relapse (30%), can repeat the regimen. G-CSF added in severe neutropenia: If > 7 days of a stretch → Malignancy. If there is no response to Immunosuppressants/Serious Side Effects we need to use alternate therapy.
  • HLA-matched unrelated BMT or Cord blood transplant
  • High-dose Cyclophosphamide with/without cyclosporine

Newer Therapies for Refractory AA

• Eltrombopag
• Alemtuzumab (Anti-CD52)

Prognosis

Spontaneous recovery from pancytopenia rarely occurs. If left untreated, severe pancytopenia has an overall mortality rate of approximately 50% within 6 months of diagnosis and of >75% overall. Infection and hemorrhage are the major causes of morbidity and mortality. Children responding to HSCT and/or immunosuppressive regimens early usually have a good outcome. 65-70% have good survival if they come to early attention.

Hope you found this blog helpful for your E-learning for NEET SS Pediatrics. For more informative and interesting posts like these, keep reading PrepLadder’s blogs. 

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