What is the management approach for a patient with iron deficiency anemia and an elevated platelet count?

Management of Iron Deficiency Anemia with Elevated Platelet Count

The elevated platelet count in iron deficiency anemia is a reactive phenomenon that requires no specific treatment and will normalize with iron replacement therapy alone. 1, 2, 3

Understanding the Thrombocytosis

The thrombocytosis associated with iron deficiency anemia is reactive, not pathologic, and can be surprisingly severe:

• Platelet counts can exceed 1,000 × 10⁹/L in severe iron deficiency, with documented cases reaching 1,703-1,953 × 10⁹/L. 2, 3
• The mechanism likely involves elevated erythropoietin (EPO) cross-stimulating megakaryocyte production, though the exact pathophysiology remains incompletely understood. 4
• The platelet count normalizes spontaneously once hemoglobin and iron stores are repleted, typically without any platelet-directed therapy. 2, 3

Critical Diagnostic Algorithm

Step 1: Confirm Iron Deficiency

• Serum ferritin <45 mg/dL is diagnostic of iron deficiency. 1
• Microcytic anemia (low MCV) with elevated red cell distribution width (RDW) supports the diagnosis. 5

Step 2: Identify the Underlying Cause

For men and postmenopausal women:

• All patients require bidirectional gastrointestinal investigation with upper endoscopy (including small bowel biopsies) and colonoscopy to exclude malignancy. 5, 1
• Screen for celiac disease in all patients regardless of typical symptoms, as it is a common cause of iron malabsorption. 1, 2

For premenopausal women:

• Women over 45 years require full GI investigation as above. 1
• Women under 45 years without upper GI symptoms may defer upper endoscopy but still need celiac screening and colonoscopy if indicated. 1
• Hemoglobin <10 g/dL suggests more serious disease requiring urgent investigation regardless of age. 1

Step 3: Rule Out Primary Hematologic Disease (When Appropriate)

While extreme thrombocytosis (>1,000 × 10⁹/L) may raise concern for essential thrombocythemia or other myeloproliferative neoplasms, bone marrow evaluation is only warranted if:

• Iron deficiency is not confirmed, or
• Platelet count fails to normalize after iron repletion. 2, 3

Common pitfall: Do not initiate cytoreductive therapy for thrombocytosis before confirming or excluding iron deficiency, as this represents unnecessary treatment. 3

Iron Replacement Strategy

Oral Iron Therapy (First-Line)

• Start with ferrous sulfate 200 mg once daily (containing 65 mg elemental iron). 1
• Add vitamin C 500 mg with each dose to enhance absorption. 1
• Expect hemoglobin to rise by 2 g/dL after 3-4 weeks of treatment. 1
• Continue oral iron for 3 months after hemoglobin normalizes to fully replenish iron stores. 1

Critical pitfall to avoid: Do not prescribe excessive daily doses (>200 mg elemental iron), as this increases side effects and paradoxically reduces absorption due to hepcidin elevation. 1

Intravenous Iron Therapy (Second-Line)

Indications for IV iron: 1

• Intolerance to at least two different oral iron preparations
• Contraindication to oral iron
• Ineffective oral iron therapy
• Modern formulations allow 1-2 infusions rather than multiple treatments. 1

Monitoring and Expected Response

• Platelet count normalizes as hemoglobin and iron stores are repleted, typically within weeks to months of initiating therapy. 2, 3
• Recheck complete blood count and iron studies at 3-4 weeks to confirm response. 1
• Do not prematurely discontinue iron before stores are fully replenished, as this leads to rapid recurrence. 1

Special Clinical Scenarios

Post-bariatric surgery patients:

• Have particularly high risk of severe iron deficiency with extreme thrombocytosis due to malabsorption. 3
• Require regular monitoring and often need IV iron therapy. 3

Celiac disease:

• Can present with severe iron deficiency and extreme thrombocytosis even without typical GI symptoms. 2
• Requires lifelong gluten-free diet in addition to iron replacement. 2