What is the appropriate diagnostic and treatment approach for a patient with microcytic anemia and thrombocytosis?

Diagnostic and Treatment Approach for Microcytic Anemia with Thrombocytosis

The combination of microcytic anemia and thrombocytosis most commonly indicates iron deficiency anemia, as thrombocytosis is a well-recognized reactive phenomenon in iron deficiency that resolves with iron supplementation. 1

Initial Diagnostic Workup

Serum ferritin is your first and most powerful diagnostic test:

• Ferritin <12 μg/dL is diagnostic of iron deficiency and requires no further testing to confirm the diagnosis 2
• Ferritin 12-100 μg/dL may still indicate iron deficiency if inflammation, malignancy, or liver disease is present (ferritin is an acute phase reactant) 2
• Ferritin >100 μg/dL essentially excludes iron deficiency 2
• For optimal sensitivity and specificity in practice, use a ferritin cut-off of 45 μg/L 3

Add transferrin saturation (TSAT) if ferritin appears falsely elevated:

• TSAT <30% supports iron deficiency diagnosis 2
• TSAT <20% with ferritin >100 μg/L indicates anemia of chronic disease, not iron deficiency 4

Use RDW to differentiate causes:

• RDW >14.0% with low MCV strongly suggests iron deficiency anemia 3
• RDW ≤14.0% with low MCV suggests thalassemia trait 3
• Elevated red cell count with microcytosis also points toward thalassemia rather than iron deficiency 2

Understanding the Thrombocytosis

Thrombocytosis in this context is reactive and benign:

• Iron deficiency commonly causes reactive thrombocytosis, which can occasionally be extreme (>2500 × 10⁹/L) 1
• The thrombocytosis resolves rapidly with iron supplementation and requires no specific treatment 1
• Reactive leukocytosis may also accompany severe iron deficiency, though this is exceptional 1

Critical pitfall: Do not confuse this presentation with thrombotic microangiopathy (TMA) or myeloproliferative disorders. TMA presents with microangiopathic hemolytic anemia (schistocytes on smear) and thrombocytopenia, not thrombocytosis 5.

Investigating the Underlying Cause

Once iron deficiency is confirmed, you must identify the source of iron loss:

• Men with hemoglobin <110 g/L or non-menstruating women with hemoglobin <100 g/L warrant fast-track gastrointestinal referral 3
• Investigation should be considered at any level of anemia with confirmed iron deficiency 3
• Common sources include gastrointestinal blood loss (including NSAID use), menstrual blood loss, malabsorption disorders (celiac disease, H. pylori, atrophic gastritis), or dietary inadequacy 4, 3
• Endoscopy is recommended for patients with gastrointestinal symptoms 3
• Screen for celiac disease if malabsorption is suspected 3

Treatment Algorithm

First-line treatment is oral iron supplementation:

• Ferrous sulfate 200 mg three times daily for at least three months after correction of anemia to replenish iron stores 3
• Alternative formulations (ferrous gluconate or ferrous fumarate) if ferrous sulfate is not tolerated 3
• Adding ascorbic acid enhances iron absorption 3
• Expected response: hemoglobin rise ≥10 g/L within 2 weeks confirms iron deficiency 3

If oral iron fails after 2-4 weeks, consider:

• Non-compliance, ongoing blood loss, or malabsorption 3
• Switch to intravenous iron (iron sucrose or iron gluconate) if malabsorption is confirmed, with expected hemoglobin increase of at least 2 g/dL within 4 weeks 3
• Order hemoglobin electrophoresis if microcytosis persists with normal iron studies, appropriate ethnic background, or MCV disproportionately low relative to anemia degree 3
• Consider rare genetic disorders (IRIDA, SLC11A2 defects) if remarkably low TSAT with low-to-normal ferritin and failure to respond to both oral and intravenous iron 3, 4

Monitoring

• Check hemoglobin and red cell indices at three-monthly intervals for one year, then after a further year 3
• Provide additional oral iron if hemoglobin or MCV falls below normal 3
• Monitor for iron overload in patients receiving multiple transfusions or long-term therapy 3

Key pitfall to avoid: Do not assume all microcytic anemia is iron deficiency. Anemia of chronic disease, thalassemia, and sideroblastic anemia must be differentiated to avoid unnecessary iron therapy 3. However, in the specific context of microcytic anemia with thrombocytosis, iron deficiency is by far the most likely diagnosis 1.