What is the management approach for a patient with aplastic anemia?

Management of Aplastic Anemia

The management of aplastic anemia requires immediate immunosuppressive therapy with anti-thymocyte globulin (ATG) plus cyclosporine as first-line treatment for patients who are not candidates for bone marrow transplantation. 1

Initial Diagnostic Workup

• Complete history focusing on potential causes including:

  • Exposure to radiation, toxins, and recent viral infections 1
  • Previous lymphocyte-depleting therapies (fludarabine, ATG, steroids, cytotoxic chemotherapy) 1
  • Personal or family history of autoimmune disease 1

• Physical examination with special attention to:

  • Spleen size to rule out other hematologic conditions 1
  • Signs of bleeding or infection 2

• Laboratory investigations:

  • Complete blood count with differential, peripheral smear, and reticulocyte count 1
  • Viral studies including CMV, HHV6, EBV, parvovirus, HIV 1
  • Nutritional assessments (B12, folate, iron, copper, ceruloplasmin, vitamin D) 1
  • Serum LDH and renal function 1
  • Bone marrow biopsy and aspirate analysis to confirm diagnosis and rule out other conditions 1
  • Flow cytometry to evaluate for paroxysmal nocturnal hemoglobinuria (PNH) 1

Grading and Risk Stratification

Severity of aplastic anemia determines treatment approach 1:

• Mild (Grade 1): ANC > 0.5 × 10^9/L, hypocellular marrow <25%, platelets > 20,000, reticulocyte count > 20,000
• Moderate (Grade 2): Hypocellular marrow <25% and two of the following: ANC < 500, platelets < 20,000, reticulocyte count < 20,000
• Severe (Grade 3-4): ANC < 200, platelets < 20,000, reticulocyte count < 20,000, plus hypocellular marrow <25%

Treatment Algorithm

First-line Treatment Options

1. Hematopoietic Stem Cell Transplantation (HSCT):

   • First choice for young patients (<40 years) with severe aplastic anemia who have an HLA-identical sibling donor 3, 4
   • Requires HLA typing and evaluation for transplantation eligibility 1

2. Immunosuppressive Therapy:

   • First choice for patients without a matched donor or those >40 years 3, 4
   • Horse ATG plus cyclosporine is the standard regimen 1
   • Monitor weekly for improvement 1

3. Supportive Care (for all patients during treatment):

   • Transfusion support with irradiated and filtered blood products 1, 2
   • Maintain platelets above 10-20 × 10^9/L (higher threshold if bleeding) 2
   • Prophylactic antibiotics for severe neutropenia 2
   • Growth factor support as needed 1, 2

Second-line Treatment Options

For patients who fail first-line therapy:

• Repeat immunosuppression with rabbit ATG plus cyclosporine and cyclophosphamide 1
• Consider eltrombopag (thrombopoietin receptor agonist) 1, 5
  • Initial dose: 36 mg orally once daily (18 mg for patients with hepatic impairment or East/Southeast Asian ancestry) 5
  • Adjust dose to maintain platelet count >50 × 10^9/L 5
  • Maximum dose: 108 mg daily 5
  • Take without meals or with low-calcium meals 5
• Consider unrelated donor HSCT for refractory cases 4

Special Considerations

Hypoplastic Myelodysplastic Syndrome vs. Aplastic Anemia

• Distinguish between hypoplastic MDS and aplastic anemia through:
  • Cytogenetic analysis 1
  • Evaluation for dysplastic features in bone marrow 1
  • Flow cytometry for abnormal phenotypes 1

Management of Complications

• Infections:

  • Prompt evaluation and treatment of febrile episodes 2
  • Consider antifungal prophylaxis in severe neutropenia 2

• Bleeding:

  • Platelet transfusions to maintain safe levels 1, 2
  • Avoid invasive procedures when possible 2

• Iron overload:

  • Monitor ferritin levels in transfusion-dependent patients 2
  • Consider chelation therapy for patients with high ferritin levels 3

Monitoring and Follow-up

• Weekly CBC during initial treatment 1
• Monitor for response to treatment:
  • Improvement in blood counts 3
  • Reduction in transfusion requirements 3
• For patients on eltrombopag:
  • Monitor liver function tests regularly 5
  • Adjust dose based on platelet response 5
  • Consider discontinuation if no response after 16 weeks 5

Common Pitfalls

• Delaying treatment initiation while awaiting complete diagnostic workup 1
• Failure to distinguish between aplastic anemia and hypocellular MDS or leukemia 1
• Inadequate supportive care during immunosuppressive therapy 2
• Not monitoring for clonal evolution to MDS or PNH 4
• Inappropriate use of growth factors without addressing underlying immune mechanism 3