Aplastic Anemia Classification
Aplastic anemia is a bone marrow failure syndrome characterized by pancytopenia and hypocellular bone marrow due to failure of hematopoietic stem cells. 1, 2
Pathophysiologic Classification
Aplastic anemia represents a hypoproliferative anemia resulting from bone marrow failure rather than increased red cell destruction or blood loss. 2, 3 The underlying mechanisms fall into three main categories:
- Immune-mediated destruction - The most common pathophysiology involves activated type 1 cytotoxic T cells targeting hematopoietic stem cells, making this an autoimmune bone marrow failure syndrome 3
- Direct stem cell injury - Caused by toxins, radiation, or drugs that directly damage hematopoietic precursors 4
- Inherited bone marrow failure syndromes - Including telomere repair gene mutations and other genetic defects affecting stem cell function 3
Morphologic Classification
From a bone marrow cellularity perspective, aplastic anemia is classified as a hypocellular anemia with:
- Severely reduced bone marrow cellularity (<20% in severe cases, corrected for patient age) 5
- Absence of moderate to severe erythroid dysplasia and abnormal sideroblasts, distinguishing it from hypocellular myelodysplastic syndrome 5
- No clusters of immature precursors (ALIP), which would indicate hypocellular acute myeloid leukemia 5
Clinical Severity Grading
The severity classification directly impacts treatment decisions and includes mild, moderate, and severe grades defined by specific hematologic parameters including absolute neutrophil count, platelet count, and reticulocyte count. 6
Key Diagnostic Pitfalls
- Age-corrected cellularity assessment is mandatory to avoid misdiagnosis, as normal bone marrow cellularity decreases with age 5
- Careful exclusion of hypocellular MDS and AML is critical since treatment approaches differ fundamentally - immunosuppression for aplastic anemia versus chemotherapy or targeted therapy for malignancies 5
- Previous genotoxic exposures must be excluded as they can create hypocellular marrows mimicking aplastic anemia 5
- Cytogenetic abnormalities occur in only 4-15% of aplastic anemia cases (typically trisomy 8, loss of Y chromosome, del 13q or 20q), whereas deletion 5q or monosomy 7 suggests MDS rather than aplastic anemia 1