Can sideroblastic anemia cause pancytopenia?

Sideroblastic Anemia and Pancytopenia

Sideroblastic anemia by itself does not typically cause pancytopenia, but when it occurs as part of myelodysplastic syndromes (MDS), it can be associated with pancytopenia. According to the WHO classification, cases with pancytopenia and features of sideroblastic anemia should be classified as MDS-unclassified (MDS-U) rather than simple sideroblastic anemia 1.

Relationship Between Sideroblastic Anemia and Pancytopenia

• Pure sideroblastic anemia (Refractory Anemia with Ring Sideroblasts - RARS) typically presents with isolated anemia rather than pancytopenia 1
• When pancytopenia is present with ring sideroblasts, this suggests a more complex myelodysplastic process rather than simple sideroblastic anemia 1
• According to the WHO classification, cases with pancytopenia and unilineage dysplasia (including those with ring sideroblasts) should be classified as MDS-unclassified (MDS-U) 1

Pathophysiological Mechanisms

• Sideroblastic anemia with pancytopenia typically indicates involvement of multiple hematopoietic cell lines, suggesting a clonal stem cell disorder rather than an isolated erythroid abnormality 1
• In MDS with ring sideroblasts, somatic mutations (particularly in SF3B1) can affect multiple cell lineages, potentially leading to pancytopenia 2
• Case reports have documented progression from isolated sideroblastic anemia to pancytopenia with development of additional genetic abnormalities 3, 4

Diagnostic Considerations

• Bone marrow examination is essential in patients presenting with pancytopenia to identify ring sideroblasts and assess for dysplasia in multiple lineages 5
• The presence of ≥15% ring sideroblasts in erythroid precursors is diagnostic of sideroblastic anemia, but the overall diagnosis depends on whether other cell lines show dysplasia 1
• Cytogenetic studies are crucial as specific abnormalities may help confirm MDS diagnosis in cases with pancytopenia 1
• Flow cytometry may reveal aberrant phenotypic features in multiple cell lines, supporting a diagnosis of MDS rather than isolated sideroblastic anemia 1

Classification According to WHO

• Refractory Anemia with Ring Sideroblasts (RARS): Presents with anemia only, ≥15% ring sideroblasts, and erythroid dysplasia only 1
• Refractory Cytopenia with Multilineage Dysplasia (RCMD): May include ring sideroblasts but also has dysplasia in ≥10% of cells in two or more myeloid lineages 1
• MDS-Unclassified (MDS-U): Includes cases with pancytopenia and unilineage dysplasia, which could include sideroblastic features 1

Clinical Implications

• The presence of pancytopenia in a patient with sideroblastic features indicates a worse prognosis compared to isolated sideroblastic anemia 1
• Patients with pancytopenia and sideroblastic features may be at higher risk for progression to acute myeloid leukemia, especially if excess blasts are present 1
• Monitoring for disease progression is essential, as cases of sideroblastic anemia with pancytopenia may evolve to higher-risk MDS subtypes 3
• Treatment approaches differ significantly between isolated sideroblastic anemia and MDS with pancytopenia - the latter may require more aggressive interventions like hypomethylating agents 1, 6

Important Distinctions

• Not all causes of pancytopenia are related to MDS or sideroblastic anemia - other common etiologies include aplastic anemia, megaloblastic anemia, and hypersplenism 7, 5
• When evaluating pancytopenia, both bone marrow aspiration (to identify ring sideroblasts) and biopsy (to assess cellularity and architecture) should be performed 5
• Acquired sideroblastic anemia with pancytopenia should be distinguished from congenital forms like Pearson syndrome, which has distinct clinical features and management 4