How do you evaluate sideroblastic anemia?

Evaluation of Sideroblastic Anemia

The evaluation of sideroblastic anemia requires bone marrow aspiration with iron stain to identify ring sideroblasts, along with comprehensive laboratory testing to determine the underlying cause and guide appropriate management. 1

Initial Diagnostic Workup

• Perform complete blood count with peripheral blood smear evaluation - sideroblastic anemia typically presents as a hypoproductive macrocytic anemia 1
• Examine peripheral blood smear for dysplastic changes and presence of dimorphic red cell population 2
• Check iron parameters including serum ferritin, transferrin saturation, and total iron binding capacity to assess for iron overload 1, 3
• Obtain bone marrow aspiration with Prussian blue stain for iron to evaluate for ring sideroblasts (≥15% ringed sideroblasts is diagnostic) 1
• Perform bone marrow biopsy to assess cellularity, dysplasia, and exclude other disorders 1
• Order cytogenetic studies on bone marrow to identify chromosomal abnormalities 1

Essential Laboratory Tests

• Serum erythropoietin level - helps guide treatment decisions and distinguish subtypes 1
• Vitamin B12 and folate levels - to exclude nutritional deficiencies 1
• Liver function tests - to assess for liver damage from iron overload 1, 3
• Serum copper and zinc levels - deficiencies can cause reversible sideroblastic anemia 4
• Thyroid function tests - to exclude endocrine causes 1
• Lead levels - if occupational exposure is suspected 4

Genetic Testing

• Based on clinical presentation, family history, and inheritance pattern, consider genetic testing for: 3, 5
  • ALAS2 mutations - for X-linked sideroblastic anemia (most common inherited form) 1, 5
  • SLC25A38 mutations - for autosomal recessive congenital sideroblastic anemia 1, 6
  • ABCB7 mutations - for X-linked sideroblastic anemia with ataxia 1
  • GLRX5 mutations - for autosomal recessive sideroblastic anemia with iron overload 1
  • SF3B1 mutations - for acquired sideroblastic anemia associated with myelodysplastic syndrome 6

Distinguishing Acquired vs. Congenital Forms

• Acquired forms are more common and typically present later in life 4
• Consider myelodysplastic syndrome with ring sideroblasts (MDS-RS) in older patients with macrocytic anemia and dysplastic features 1
• Early onset, family history, and response to pyridoxine suggest congenital forms 6, 7
• Presence of other cytopenias or dysplastic features in other cell lines suggests MDS 1

Additional Diagnostic Considerations

• Flow cytometry to assess for paroxysmal nocturnal hemoglobinuria (PNH) clone 1
• HLA-DR15 typing may help identify patients more likely to respond to immunosuppressive therapy 1
• Reticulin staining of bone marrow to evaluate for fibrosis 1
• Erythrogram pattern from automated cell counters can be highly predictive of ring sideroblasts in bone marrow 2

Common Pitfalls to Avoid

• Failure to perform iron staining on bone marrow aspirate - essential for diagnosis 1
• Missing reversible causes of sideroblastic anemia (alcohol, drugs, copper deficiency) 4
• Not considering congenital forms in adults - some may present later in life 5
• Inadequate assessment of iron overload, which is common and requires monitoring 1, 3
• Failure to screen family members when hereditary forms are identified 1, 3

By following this systematic approach to evaluation, the underlying cause of sideroblastic anemia can be identified, allowing for appropriate management strategies including pyridoxine therapy for XLSA, erythropoietin with or without G-CSF, transfusion support, iron chelation, and consideration of stem cell transplantation in selected cases 1, 3.