How to manage a patient with persistent thrombocytosis (elevated platelet count) and a history of anemia, now resolved with iron supplements?

Management of Persistent Thrombocytosis in a Patient with Resolved Iron Deficiency Anemia

Iron supplementation should be continued while monitoring platelet count, as reactive thrombocytosis secondary to iron deficiency typically resolves with correction of the underlying iron deficiency.

Understanding the Clinical Picture

This patient presents with:

• Elevated platelet count of 429 × 10^9/L (thrombocytosis)
• Elevated RDW-CV of 16.5% (indicating red cell size variability)
• History of persistently elevated platelets (378-429 × 10^9/L) over six years
• Previously anemic, now resolved with iron supplementation
• Current iron levels within normal limits

Diagnostic Assessment

Classification of Thrombocytosis

1. Reactive (Secondary) Thrombocytosis

   • Most likely diagnosis in this case
   • Common causes include iron deficiency anemia, inflammation, infection, and tissue damage 1
   • Typically resolves when the underlying condition is treated

2. Primary (Clonal) Thrombocytosis

   • Part of myeloproliferative neoplasms (MPNs) such as essential thrombocythemia
   • Usually presents with platelet counts >600 × 10^9/L 2
   • Requires bone marrow examination and genetic testing for confirmation

Significance of Laboratory Values

• RDW-CV of 16.5%: Elevated RDW indicates variation in red cell size, commonly seen in:

  • Recent iron deficiency (even when hemoglobin has normalized)
  • Mixed nutritional deficiencies
  • Inflammatory conditions 1

• Platelet count of 429 × 10^9/L:

  • Mild thrombocytosis (normal range typically 150-400 × 10^9/L)
  • Below the threshold of 600 × 10^9/L typically used to diagnose essential thrombocythemia 2

Management Approach

Immediate Management

1. Continue iron supplementation

   • Even though iron levels are currently normal, continue supplementation for at least 3 months after correction of anemia to replenish iron stores
   • Target ferritin level should be at least 100 ng/mL 1

2. Monitor complete blood count

   • Check CBC, including platelet count and RDW, every 4-6 weeks
   • Expect gradual normalization of platelet count with continued iron therapy 1

Further Evaluation

1. Assess for ongoing blood loss

   • Given the history of anemia requiring iron supplementation, evaluate for potential sources of blood loss
   • Consider menstrual history, gastrointestinal bleeding, or other sources of chronic blood loss

2. Consider additional testing if thrombocytosis persists

   • If platelet count remains elevated after 3 months of adequate iron therapy:
     • Check inflammatory markers (CRP, ESR)
     • Consider bone marrow examination if platelet count increases or other cytopenias develop 3

When to Consider Cytoreductive Therapy

Cytoreductive therapy is generally not indicated for reactive thrombocytosis but may be considered in:

1. Extreme thrombocytosis (>1,000/μL) due to risk of acquired von Willebrand syndrome 3

2. High-risk patients with:

   • History of thrombotic events
   • Additional cardiovascular risk factors
   • Symptoms attributable to thrombocytosis 3

For this patient with mild thrombocytosis (429 × 10^9/L) and no reported thrombotic symptoms, cytoreductive therapy is not indicated.

Prognosis and Follow-up

• Reactive thrombocytosis secondary to iron deficiency typically resolves within weeks to months after iron repletion 4, 5
• Complete normalization of RDW may take longer than hemoglobin normalization
• If thrombocytosis persists despite adequate iron therapy for 3-6 months, consider hematology consultation

Common Pitfalls to Avoid

1. Misdiagnosing essential thrombocythemia

   • Reactive thrombocytosis is much more common than essential thrombocythemia
   • Avoid unnecessary bone marrow biopsies in patients with clear secondary causes

2. Discontinuing iron too early

   • Iron therapy should continue for at least 3 months after normalization of hemoglobin
   • Premature discontinuation may lead to recurrence of iron deficiency and thrombocytosis

3. Initiating cytoreductive therapy unnecessarily

   • Medications like anagrelide should be reserved for confirmed essential thrombocythemia or extreme thrombocytosis with complications 2

4. Overlooking ongoing blood loss

   • Always investigate the underlying cause of iron deficiency, especially in patients requiring ongoing supplementation

5. Failing to recognize that iron deficiency can cause both thrombocytosis and thrombocytopenia

   • While thrombocytosis is more common, severe iron deficiency can occasionally cause thrombocytopenia 4, 6