What is aplastic anemia?

Aplastic Anemia: Definition and Diagnostic Approach

Aplastic anemia is a bone marrow failure syndrome characterized by severely reduced bone marrow cellularity (<20% in severe cases) and peripheral blood pancytopenia, resulting from the loss of hematopoietic stem cells that are replaced by fat cells. 1, 2

Pathophysiology

• Aplastic anemia results from three main mechanisms of bone marrow destruction: direct injury, immune-mediated damage, and inherited or clonal bone marrow failure disorders 3
• The most common form is immune-mediated, where activated type 1 cytotoxic T cells attack hematopoietic stem cells, leading to their destruction and subsequent bone marrow failure 4
• Molecular and genetic abnormalities, such as telomere repair gene mutations, have been identified as contributing factors in some cases 4

Diagnostic Criteria

• Diagnosis requires comprehensive evaluation including both peripheral blood assessment and bone marrow examination 1
• Bone marrow biopsy is essential and must show:
  • Severely reduced cellularity (<20% in severe cases), appropriately corrected for patient age 1
  • Examination of at least 100 cells to assess for dysplasia and blast percentage 1
• Peripheral blood typically shows pancytopenia (decreased red cells, white cells, and platelets) 2

Distinguishing Features from Related Disorders

• Aplastic anemia must be differentiated from other hypocellular disorders with similar presentations:
  • Hypocellular myelodysplastic syndrome (H-MDS): absence of moderate to severe erythroid dysplasia and abnormal sideroblasts in aplastic anemia 1
  • Hypocellular acute myeloid leukemia (H-AML): lacks clusters of immature precursors (ALIP) that are characteristic of H-AML 1
• The diagnostic algorithm has become increasingly complex, now incorporating molecular and genetic testing to exclude conditions with similar phenotypes 2

Clinical Presentation

• Common clinical manifestations include:
  • Fatigue and exhaustion (anemic symptoms) 5
  • Hemorrhagic manifestations (due to thrombocytopenia) 5
  • Fever and infections (due to neutropenia) 5
• Without treatment, mortality from severe aplastic anemia approaches 70% within 2 years 2

Important Clinical Considerations

• Age correction is crucial when assessing bone marrow cellularity to avoid misdiagnosis 1
• Previous genotoxic exposure or therapy must be excluded as they can cause hypocellular marrows resembling aplastic anemia 1
• The disease appears with almost equal frequency in men and women, with two age peaks: younger than 30 years and over 60 years 5
• Careful exclusion of hypocellular variants of MDS and AML is critical, as treatment approaches differ significantly 1

Treatment Approaches

• For patients younger than 50 years with a matched sibling donor, allogeneic hematopoietic stem cell transplantation is the treatment of choice and potential cure 2
• For those without a suitable donor, immunosuppressive therapy is the mainstay of treatment, typically using:
  • Equine antithymocyte globulin
  • Cyclosporine A
  • Eltrombopag 2
• Supportive care with blood product transfusions is an important component of management 2, 6
• Survival outcomes have significantly improved with modern treatment approaches compared to historical outcomes 4