Does Aplastic Anemia Cause Leukopenia?
Yes, aplastic anemia definitively causes leukopenia as part of its characteristic pancytopenia presentation. 1
Pathophysiology and Clinical Presentation
Aplastic anemia is a hematopoietic stem-cell disorder that results in pancytopenia (reduction in all three blood cell lines) and hypocellular bone marrow. 2 The clinical features specifically include:
- Leukopenia (reduced white blood cell count, particularly neutropenia)
- Anemia (reduced red blood cells causing fatigue)
- Thrombocytopenia (reduced platelets causing bleeding/bruising) 3, 2
The leukopenia in aplastic anemia places patients at high risk for infection due to reduced neutrophil counts, which is one of the major clinical concerns requiring close monitoring. 3
Mechanism of Cytopenia Development
The underlying pathophysiology involves:
- Immune-mediated destruction of hematopoietic stem cells by autoreactive T lymphocytes in most acquired cases 2, 4
- Bone marrow hypocellularity with replacement of normal cellular elements by fat 5
- Trilineage bone marrow failure affecting all blood cell production simultaneously 5
This is not a selective process—the stem cell destruction affects production of all blood cell types, making leukopenia an invariable feature rather than an occasional finding. 2, 4
Clinical Significance and Monitoring
Critical neutrophil thresholds that guide clinical management include:
- Neutrophil counts <2,000/μL indicate significant immunocompromise requiring infection prophylaxis 3
- Severe neutropenia substantially increases risk of systemic infection, particularly with concurrent local infections 3
- Patients require close monitoring of neutrophil counts before any invasive procedures 3
Diagnostic Considerations
When evaluating pancytopenia with leukopenia, aplastic anemia must be distinguished from:
- Hypocellular myelodysplastic syndrome (H-MDS) - both present with pronounced cytopenia and hypocellular marrow 1
- Hypocellular acute myeloid leukemia (H-AML) - can mimic aplastic anemia clinically 1
Bone marrow biopsy is critical and necessary for definitive diagnosis, showing severely reduced cellularity (<20% in severe cases, age-corrected) without dysplasia or abnormal blast clusters. 6
Common Pitfall
Do not assume leukopenia with hypocellular marrow automatically equals aplastic anemia—hypocellular variants of MDS and AML can present identically and require different treatment approaches. 6 The key distinguishing features include absence of moderate-to-severe dysplasia, absence of abnormal sideroblasts, and absence of abnormal localization of immature precursors (ALIP). 6