What are the next steps in managing a patient with mild anemia and thrombocytosis?

Management of Mild Microcytic Anemia with Thrombocytosis

The immediate next step is to measure serum ferritin and transferrin saturation (TSAT) to confirm iron deficiency anemia, which is the most likely diagnosis given the microcytic hypochromic pattern (low MCH, low MCHC) with elevated RDW and reactive thrombocytosis. 1

Diagnostic Interpretation

Your CBC reveals a classic pattern of iron deficiency anemia:

• Microcytic hypochromic anemia: Hemoglobin 11.6 g/dL (low), MCV 82.8 fL (normal-low), MCH 25.6 pg (low), MCHC 30.9 g/dL (low) 1
• Elevated RDW 16.0%: This reflects heterogeneous red cell sizes characteristic of iron deficiency, distinguishing it from thalassemia trait 2
• Reactive thrombocytosis (425,000/μL): Platelet elevation is a well-documented response to iron deficiency and typically resolves with iron repletion 3, 4, 5

The combination of microcytosis with elevated RDW strongly favors iron deficiency over thalassemia trait, which typically shows normal RDW 2.

Immediate Diagnostic Workup

Order the following tests immediately:

• Serum ferritin: Levels <30 μg/L confirm iron deficiency; in the presence of inflammation, ferritin up to 100 μg/L may still represent true iron deficiency 1, 2
• Transferrin saturation (TSAT): TSAT <16% indicates absolute iron deficiency 1
• Reticulocyte count: Should be appropriately elevated in iron deficiency (unlike bone marrow suppression) 6

Treatment Strategy

Once iron deficiency is confirmed (ferritin <30 μg/L or TSAT <20%):

• Initiate oral iron therapy: Ferrous sulfate 200 mg three times daily for at least 3 months after hemoglobin correction 1, 2
• Investigate the source of iron loss: In adults, this requires evaluation for gastrointestinal blood loss (particularly malignancy in men and postmenopausal women) or menstrual losses in premenopausal women 2
• Do NOT treat empirically without confirming iron deficiency, as inappropriate iron supplementation in thalassemia trait can cause iron overload 2

Management of Thrombocytosis

The elevated platelet count requires no specific intervention:

• Reactive thrombocytosis in iron deficiency typically resolves spontaneously with iron repletion, even when extreme (>1000×10⁹/L) 4, 5
• Thrombocytosis up to 2500×10⁹/L has been reported with severe iron deficiency and normalized with iron supplementation alone 4
• Cytoreductive therapy is NOT indicated for reactive thrombocytosis secondary to iron deficiency 5

Thrombotic Risk Considerations

While thrombocytosis is associated with iron deficiency, the actual thrombotic risk remains controversial:

• Case reports document cerebral venous thrombosis in children with iron deficiency and thrombocytosis 7
• However, plasma viscosity studies show no significant increase despite elevated platelet counts in iron deficiency 3
• No prophylactic anticoagulation is recommended unless other thrombotic risk factors are present 3

Monitoring and Follow-Up

Recheck CBC, ferritin, and TSAT at 2-4 weeks:

• Expect hemoglobin increase ≥1.0 g/dL within 2-4 weeks if iron deficiency is contributing 1
• Platelet count should begin normalizing as anemia improves 4, 5
• Monitor hemoglobin and red cell indices at 3-month intervals for one year, then annually 1, 2

If no response to oral iron after 2-4 weeks:

• Consider intravenous iron if malabsorption is suspected (history of bariatric surgery, celiac disease, inflammatory bowel disease) 1, 5
• Reassess for ongoing blood loss 2

Critical Pitfalls to Avoid

• Do not assume myeloproliferative neoplasm based on thrombocytosis alone—the microcytic anemia pattern argues strongly against essential thrombocythemia, which typically presents with normal or elevated hemoglobin 8, 5
• Do not initiate cytoreductive therapy (hydroxyurea, aspirin) for reactive thrombocytosis—this resolves with iron repletion 8, 5
• Do not overlook gastrointestinal malignancy as the source of iron loss, particularly in men and postmenopausal women 2

When to Consider Alternative Diagnoses

If ferritin is normal or elevated (>100 μg/L) with TSAT <20%:

• Consider anemia of chronic disease/inflammation 1
• Evaluate for underlying inflammatory, infectious, or malignant conditions 1

If standard workup is unrevealing and anemia persists despite treatment:

• Consider genetic disorders of iron metabolism (rare), particularly with extreme microcytosis (MCV <70 fL) or family history of refractory anemia 8, 1
• Hematology referral is appropriate at this stage 9