What is the appropriate management for a patient with thrombocytosis and elevated RDW(SD)?

Management of Thrombocytosis with Elevated RDW(SD)

This patient requires investigation for reactive thrombocytosis and evaluation for iron deficiency or early iron-restricted erythropoiesis, despite normal hemoglobin and MCV, as the elevated RDW(SD) of 50.2 indicates significant red cell size heterogeneity that warrants further workup.

Interpretation of Laboratory Findings

Thrombocytosis (Platelet Count 522)

• Reactive thrombocytosis is the most likely diagnosis given the isolated platelet elevation without other myeloproliferative features 1
• Common causes include inflammation, infection, iron deficiency, malignancy, or tissue damage 1
• The normal white blood cell count and differential make primary myeloproliferative disorders less likely but do not exclude them 1

Elevated RDW(SD) of 50.2

• This markedly elevated RDW(SD) indicates significant anisocytosis (red cell size variation) that typically reflects either active erythropoiesis, nutritional deficiency, or chronic disease 2
• An elevated RDW with normal MCV and hemoglobin suggests early or evolving iron deficiency, mixed deficiency states, or chronic inflammation 2
• The RDW(CV) of 14.2% is at the upper limit of normal (>14.0% is considered elevated), which corroborates the RDW(SD) finding 2

Diagnostic Workup Algorithm

First-Line Testing (Obtain Immediately)

• Serum ferritin concentration - most powerful test for iron deficiency; <30 μg/L indicates iron deficiency in absence of inflammation 2
• Transferrin saturation - values <30% suggest iron-restricted erythropoiesis 2
• C-reactive protein (CRP) - to assess for inflammation that may elevate ferritin and cause reactive thrombocytosis 2
• Peripheral blood smear - to evaluate red cell morphology, platelet morphology, and exclude hemolysis or hemoglobinopathy 3

Interpretation Based on Ferritin and Inflammation Status

If ferritin <30 μg/L without inflammation (normal CRP):

• Confirms iron deficiency 2
• Investigate gastrointestinal blood loss as primary cause in adults 2
• Consider upper endoscopy and colonoscopy, particularly in men and postmenopausal women 2
• Evaluate for celiac disease with tissue transglutaminase antibodies 2

If ferritin 30-100 μg/L with elevated CRP:

• Iron deficiency may still be present despite inflammation elevating ferritin into "normal" range 2
• Transferrin saturation <30% supports functional iron deficiency 2
• Consider trial of iron supplementation with reassessment in 3 weeks 2

If ferritin >100 μg/L:

• Iron deficiency is unlikely 2
• Elevated RDW may reflect chronic inflammation, oxidative stress, or early myeloproliferative process 1, 4
• Proceed to evaluation for primary thrombocytosis (see below)

Management of Thrombocytosis

Reactive Thrombocytosis (Most Likely)

• No specific treatment for platelet elevation itself if reactive and platelet count <1000 × 10⁹/L 1
• Treat underlying cause (iron deficiency, inflammation, infection) 1
• Platelet count typically normalizes when underlying condition resolves 1
• No increased thrombotic risk with reactive thrombocytosis at this level 1

Evaluation for Primary Thrombocytosis (If Ferritin >100 μg/L and No Clear Reactive Cause)

• JAK2 V617F mutation testing - positive in ~50-60% of essential thrombocythemia 1
• CALR and MPL mutation testing if JAK2 negative 1
• Bone marrow biopsy may be needed if mutations positive or clinical suspicion high 1
• Hematology consultation recommended if myeloproliferative disorder suspected 3

Iron Deficiency Management (If Confirmed)

Iron Supplementation

• Oral ferrous sulfate 325 mg (65 mg elemental iron) daily or every other day for better absorption and tolerability 2
• Continue for 3-6 months after hemoglobin normalizes to replete iron stores 2
• Recheck complete blood count, ferritin, and RDW in 3 weeks to confirm response 2

Expected Response

• RDW typically increases transiently during early iron replacement as new normocytic cells mix with existing microcytic cells 2
• Hemoglobin should increase by ~1 g/dL after 3 weeks of therapy 2
• Platelet count should normalize as iron stores replete 1

Critical Pitfalls to Avoid

• Do not dismiss elevated RDW when hemoglobin and MCV are normal - this pattern suggests early or evolving deficiency 2, 3
• Do not rely on ferritin alone in presence of inflammation - ferritin 30-100 μg/L may mask iron deficiency when CRP elevated 2
• Do not assume reactive thrombocytosis without investigating the cause - iron deficiency and malignancy must be excluded 2, 1
• Do not empirically treat with iron without confirming deficiency - inappropriate iron supplementation can be harmful 3
• Do not overlook gastrointestinal investigation in adults with confirmed iron deficiency, as occult GI blood loss (including malignancy) is the most common cause 2

Follow-Up Strategy

• Recheck CBC with RDW in 3 weeks after initiating iron therapy (if iron deficient) 2
• If no improvement after 3 weeks of iron, consider malabsorption (celiac disease), ongoing blood loss, or incorrect diagnosis 2
• Monitor platelet count - should normalize within 1-2 months if reactive to iron deficiency 1
• If thrombocytosis persists despite treating underlying cause, pursue myeloproliferative workup 1