How to manage a patient with iron deficiency anemia, thrombocytosis, and eosinophilia?

Management of Iron Deficiency Anemia with Thrombocytosis and Eosinophilia

Treat the iron deficiency anemia with oral ferrous sulfate 200 mg three times daily while simultaneously investigating the underlying cause through comprehensive GI evaluation, as the thrombocytosis is likely reactive to the iron deficiency and will resolve with treatment, while the eosinophilia requires separate diagnostic consideration. 1

Understanding the Clinical Triad

Thrombocytosis in Iron Deficiency

• Reactive thrombocytosis commonly accompanies iron deficiency anemia and typically resolves once the anemia is corrected. This is a well-recognized phenomenon where platelet counts can be significantly elevated (often >450,000/μL) as a reactive process.
• The thrombocytosis itself does not require specific treatment and should normalize within weeks to months after iron repletion begins.
• Monitor platelet counts during follow-up to confirm they decrease as hemoglobin rises—if platelets remain elevated after anemia correction, consider alternative causes of thrombocytosis.

Eosinophilia Considerations

• Eosinophilia in the context of iron deficiency anemia raises specific diagnostic possibilities that require investigation:
  • Parasitic infections (hookworm, strongyloides) can cause both GI blood loss leading to iron deficiency AND eosinophilia
  • Celiac disease should be evaluated with antiendomysial antibody testing (and IgA levels to exclude IgA deficiency) 1
  • Inflammatory bowel disease (particularly eosinophilic gastroenteritis)
  • Drug reactions (NSAIDs can cause both GI bleeding and eosinophilia)

Immediate Treatment Approach

Iron Supplementation

All patients require iron supplementation to correct anemia and replenish body stores, achieved with ferrous sulfate 200 mg three times daily. 1

• Alternative formulations (ferrous gluconate, ferrous fumarate) are equally effective if ferrous sulfate is not tolerated 1
• Add ascorbic acid if response is poor to enhance iron absorption 1
• Reserve parenteral iron only for intolerance to at least two oral preparations or documented non-compliance 1
• Expect hemoglobin to rise by 2 g/dL after 3-4 weeks 1
• Continue iron for three months after anemia correction to replenish stores 1

Common Pitfalls in Iron Therapy

• Failure to respond is usually due to: poor compliance, misdiagnosis, continued blood loss, or malabsorption 1
• Do not use parenteral iron as first-line—it is painful, expensive, carries anaphylaxis risk, and provides no faster hemoglobin rise than oral therapy 1

Diagnostic Investigation Algorithm

Age-Based Stratification

For patients >45 years old:

• Perform both upper GI endoscopy with small bowel biopsy AND colonoscopy (or barium enema) unless a firm cause is identified with the first investigation 1
• This dual approach is critical as 90% of patients should receive complete GI evaluation 1

For patients <45 years old:

• Upper GI endoscopy with small bowel biopsy if upper GI symptoms present 1
• Antiendomysial antibody testing (with IgA measurement) for all others to exclude celiac disease 1
• Colonoscopy only if specific indications exist (change in bowel habit, rectal bleeding) 1

Special Considerations for This Triad

Given the eosinophilia, prioritize the following during investigation:

1. Small bowel biopsy during upper endoscopy is mandatory to evaluate for:

   • Celiac disease (which explains both iron deficiency and can be associated with eosinophilia) 1
   • Eosinophilic gastroenteritis
   • Parasitic infections

2. Stool examination for ova and parasites should be performed, particularly if there is travel history or risk factors for parasitic infection

3. Review medication history carefully—NSAIDs can cause occult GI bleeding leading to iron deficiency while also triggering eosinophilia 1

Follow-Up Protocol

Monitor hemoglobin and red cell indices:

• Every 3 months for the first year 1
• Once more after an additional year 1
• Give additional oral iron if hemoglobin or MCV falls below normal 1

Further investigation is only necessary if hemoglobin and MCV cannot be maintained with supplementation 1

Resolution of anemia should be achieved by 6 months in 80% of patients 1

When Standard Workup is Negative

If initial GI evaluation is unrevealing and anemia persists:

• Further small bowel visualization is not necessary unless the anemia is transfusion-dependent or there is visible blood loss 1
• Enteroscopy may be helpful in transfusion-dependent cases to detect small bowel angiodysplasia 1
• Small bowel radiology is rarely useful unless Crohn's disease is suspected 1

Important Caveats

• Faecal occult blood testing has no diagnostic value—it is insensitive and non-specific 1
• Routine liver function, renal function, and clotting studies are not diagnostically valuable unless systemic disease is suspected 1
• Exclude urinary tract sources if hematuria is present 1

Expected Outcomes

• Thrombocytosis should resolve as iron stores are replenished—this typically occurs within 2-3 months of starting therapy
• If platelet counts remain elevated after anemia correction, investigate for primary myeloproliferative disorders
• Eosinophilia resolution depends on the underlying cause—if reactive to parasitic infection or celiac disease, it should improve with treatment of the primary condition
• If eosinophilia persists despite anemia correction and negative GI workup, consider hematology referral for primary eosinophilic disorders