What investigations should I do for a 38-year-old female with normocytic normochromic anemia, eosinophilia, normal white blood cell count (WBC), and no evidence of hemoparasites, with a hemoglobin level of 9.7 g/dL?

Investigation Protocol for Normocytic Normochromic Anemia with Eosinophilia

For a 38-year-old female with normocytic normochromic anemia (Hb 9.7 g/dL), eosinophilia, normal WBC count, and no hemoparasites, a systematic diagnostic approach focusing on potential causes of eosinophilia should be initiated, as this is likely the key to diagnosing the underlying condition.

Initial Laboratory Investigations

• Complete blood count with differential (to confirm eosinophilia and assess other cell lines)
• Peripheral blood smear review (to evaluate blood cell morphology and confirm absence of hemoparasites)
• Comprehensive metabolic panel with liver function tests (to assess organ function)
• Serum tryptase levels and vitamin B12 levels 1 (elevated in myeloproliferative variants of hypereosinophilia)
• Erythrocyte sedimentation rate and C-reactive protein (to assess inflammation)
• Serum immunoglobulin levels including IgE 1 (may be elevated in allergic disorders and lymphocytic variants of hypereosinophilic syndrome)

Specific Tests for Eosinophilia Evaluation

• Parasite serology 1:

  • Strongyloides serology (most common parasitic cause of eosinophilia)
  • Toxocara serology (visceral larva migrans)
  • Schistosomiasis serology
  • Filariasis testing

• Autoimmune workup 1:

  • Antineutrophil cytoplasmic antibodies (ANCA)
  • Antinuclear antibodies (ANA)

• Stool studies 1:

  • Ova and parasite examination (3 samples)
  • Gastrointestinal PCR for parasites

• Bone marrow aspiration and biopsy 1 with:

  • Immunohistochemistry for CD117, CD25, tryptase
  • Reticulin/collagen stains for fibrosis
  • Conventional cytogenetics
  • Fluorescence in situ hybridization (FISH) and/or RT-PCR to detect tyrosine kinase fusion gene rearrangements

Advanced Testing Based on Initial Results

• Molecular testing 1:

  • PDGFRA, PDGFRB, FGFR1, and PCM1-JAK2 rearrangements
  • Next-generation sequencing via myeloid mutation panels (to establish clonality)

• Serum protein electrophoresis and immunofixation 1:

  • To rule out monoclonal gammopathy
  • 24-hour urine protein electrophoresis and immunofixation

• Imaging studies 1:

  • Consider PET/CT scan or whole-body MRI to evaluate for occult malignancy or organ involvement

Diagnostic Categories to Consider

1. Primary (clonal/neoplastic) hypereosinophilia 1, 2:

   • Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase fusion genes
   • Chronic eosinophilic leukemia, not otherwise specified (CEL-NOS)

2. Secondary (reactive) hypereosinophilia 1, 2:

   • Parasitic infections
   • Allergic disorders
   • Drug reactions
   • Autoimmune disorders

3. Idiopathic hypereosinophilic syndrome 1, 2:

   • Diagnosis of exclusion after ruling out primary and secondary causes

4. Anemia-specific investigations 1, 3:

   • Iron studies (serum iron, ferritin, TIBC)
   • Hemolysis workup (LDH, haptoglobin, reticulocyte count, direct Coombs test)
   • Renal function tests (to rule out chronic kidney disease)

Important Considerations

• The combination of normocytic normochromic anemia with eosinophilia should raise suspicion for myeloproliferative disorders, particularly those with PDGFRA, PDGFRB, or FGFR1 rearrangements 1
• Bone marrow examination is essential in this case as it can identify clonal disorders that may require specific targeted therapies 1, 4
• Detailed travel history, medication review, and allergy history are crucial as they may point to secondary causes of eosinophilia 2
• In the absence of an identifiable cause, monitoring of eosinophil counts and assessment for end-organ damage is necessary 2

Pitfalls to Avoid

• Do not assume that normocytic normochromic anemia is always due to chronic disease; the presence of eosinophilia suggests a specific etiology that requires investigation
• Do not start empiric treatment before completing a thorough workup, as treatment may mask underlying conditions
• Do not miss evaluation for potential organ damage from eosinophilia, particularly cardiac involvement
• Avoid attributing eosinophilia to allergic causes without excluding other etiologies, especially in the presence of anemia

By following this systematic approach, the underlying cause of both the anemia and eosinophilia can be identified, leading to appropriate targeted therapy.