Most Common Cause of Aplastic Anemia in Adults
The most common cause of aplastic anemia in adults is immune-mediated destruction of hematopoietic stem cells, where autoreactive cytotoxic T lymphocytes attack and destroy bone marrow stem cells. 1, 2
Pathophysiology of Immune-Mediated Aplastic Anemia
The immune mechanism is well-established as the primary driver in acquired aplastic anemia:
- Oligoclonally expanded cytotoxic T cells induce apoptosis of hematopoietic progenitors through direct cellular attack. 1
- Activated dendritic cells promote Th1 polarization and activate CD8+ T cells, creating a destructive cytokine network involving IFN-gamma, TNF-alpha, and multiple interleukins that destroy stem/progenitor cells. 3
- Regulatory T cells are significantly reduced in patients' peripheral blood, removing normal immune suppression mechanisms. 1
- T-bet, a transcription factor binding to the interferon-gamma promoter region, is upregulated in aplastic anemia T cells. 1
Why the Other Options Are Incorrect
Inherited Abnormalities
- Inherited bone marrow failure syndromes (Fanconi anemia, telomere disorders) are more common in pediatric cases and represent only a minority of adult aplastic anemia. 4
- In adults, inherited predisposition should be assessed primarily in young adults or families with multiple cases of MDS, AML, or aplastic anemia, but this is not the typical presentation. 4
- Loss-of-function mutations in telomerase complex genes may underlie disease development in only a minority of cases. 1
Chronic High-Altitude Exposure
- This is not a recognized cause of aplastic anemia in any medical literature or guidelines. 4
- High altitude causes physiologic erythrocytosis (increased red blood cells), the opposite of aplastic anemia's pancytopenia. [General Medicine Knowledge]
Excessive Vitamin B12 Intake
- This is completely incorrect - vitamin B12 deficiency (not excess) causes megaloblastic anemia, not aplastic anemia. 4
- Laboratory evaluation for aplastic anemia specifically includes checking B12 and folate levels to exclude these nutritional deficiencies as alternative diagnoses. 4
- Excessive B12 intake has no established association with bone marrow failure. [General Medicine Knowledge]
Clinical Implications
Most acquired aplastic anemia cases are classified as idiopathic (no identifiable trigger), though environmental exposures may trigger the aberrant immune response in some patients:
- Drug exposures (chemotherapy, particularly alkylating agents and purine analogues) can trigger secondary aplastic anemia. 4
- Benzene and its derivatives from occupational exposure are recognized triggers. 4
- Viral infections may serve as triggers in some cases. 2
- Despite these potential triggers, the underlying mechanism remains immune-mediated destruction. 2
Treatment Rationale Based on Etiology
The immune-mediated pathophysiology directly informs treatment:
- Immunosuppressive therapy (antithymocyte globulin and ciclosporin) is effective because it targets the aberrant immune response. 1, 2
- Allogeneic hematopoietic stem cell transplantation is preferred for children and young adults with severe aplastic anemia. 1, 5
- High-dose cyclophosphamide provides an alternative immunosuppressive approach. 2