Common Causes of Aplastic Anemia in the Elderly
The most common causes of aplastic anemia in elderly patients include idiopathic immune-mediated mechanisms, myelodysplastic syndromes, medications, environmental toxins, and viral infections, with idiopathic immune-mediated destruction being the predominant etiology. 1
Pathophysiological Classification of Causes
1. Idiopathic/Immune-Mediated (Most Common in Elderly)
- Autoreactive lymphocytes mediate the destruction of hematopoietic stem cells 2
- Aberrant immune response leads to bone marrow failure
- Accounts for the majority of cases in elderly patients where no clear trigger is identified
2. Secondary Causes
Medications and Chemical Exposures
- Chemotherapy agents - particularly alkylating agents and purine analogues 1
- Benzene and its derivatives - industrial and occupational exposure 1
- Radiation exposure - previous radiotherapy or accidental exposure 1
- Immune checkpoint inhibitors - can cause immune-related adverse events including aplastic anemia 1
Clonal Disorders
- Myelodysplastic Syndromes (MDS) - particularly difficult to distinguish from aplastic anemia in elderly patients 1
Infectious Causes
- Viral infections - particularly hepatitis viruses, Epstein-Barr virus, HIV
- Paroxysmal nocturnal hemoglobinuria (PNH) - can present with or evolve from aplastic anemia 2
Inherited/Genetic Causes (Less Common in Elderly)
- Usually diagnosed earlier in life but may present in elderly with milder forms
- Fanconi anemia, telomerase complex gene mutations (TERC, TERT)
- Germline mutations in DDX41, GATA2, RUNX1, ANKRD26, ETV6 3
Diagnostic Approach for Aplastic Anemia in Elderly
Essential Workup
- Complete blood count - pancytopenia is characteristic
- Bone marrow biopsy and aspiration - hypocellular marrow with fatty replacement
- Cytogenetic analysis - to distinguish from MDS and identify chromosomal abnormalities 1
- Flow cytometry - to rule out PNH clone
- Medication review - identify potential drug-induced causes
Distinguishing from MDS
- Karyotype abnormalities are seen in 4-15% of aplastic anemia cases with successful cytogenetic analysis 1
- The presence of deletion 5q or -7 is often considered presumptive evidence for MDS rather than pure aplastic anemia 1
- Cytogenetic investigation typically involves conventional banding analysis (CBA) but may fail in up to 50% of cases due to insufficient metaphases 1
Management Considerations
Age-Specific Challenges
- Elderly patients have inferior outcomes following immunosuppressive therapy compared to younger patients 4
- Presence of comorbidities significantly impacts treatment decisions and outcomes 4
- Quality of life considerations are particularly important in this age group 4
Treatment Options
- Immunosuppressive therapy - antithymocyte globulin and cyclosporine 2
- Supportive care - transfusions, growth factors, infection prevention
- Hematopoietic stem cell transplantation - limited role in elderly due to increased risks
- Removal of potential causative agents - discontinuation of suspected medications
Clinical Pearls and Pitfalls
- Diagnostic challenge: Up to 50% of aplastic anemia cases result in karyotype failures or inconclusive cytogenetic analyses due to insufficient metaphases 1
- Evolving disease: Paroxysmal nocturnal hemoglobinuria and myelodysplastic syndrome commonly arise in patients with aplastic anemia, showing a pathophysiological link between these disorders 2
- Multiple etiologies: Older patients are more likely than younger ones to have more than one contributing cause to their aplastic anemia
- Treatment toxicity: Elderly patients have higher rates of treatment-related mortality with intensive therapies, necessitating careful individual assessment 4
By understanding these common causes and their diagnostic features, clinicians can better approach the evaluation and management of aplastic anemia in elderly patients.