How to manage elevated platelet count (thrombocytosis)?

Management of Elevated Platelet Count (Thrombocytosis)

The management of thrombocytosis should focus on identifying the underlying cause, assessing thrombotic and bleeding risks, and implementing targeted therapy based on etiology and risk stratification. The approach differs significantly between primary (clonal) and secondary (reactive) thrombocytosis.

Initial Diagnostic Workup

• Complete blood count with peripheral blood smear examination
• Rule out pseudothrombocytopenia by examining for platelet clumping
• Review of previous platelet counts
• Coagulation studies, liver and renal function tests
• Testing for HCV and HIV 1
• Consider molecular testing for JAK2, CALR, and MPL mutations if primary thrombocytosis is suspected

Classification and Causes

Primary Thrombocytosis (12.5% of cases)

• Essential thrombocythemia (ET)
• Polycythemia vera (PV)
• Primary myelofibrosis
• Other myeloproliferative neoplasms (MPNs)

Secondary Thrombocytosis (83.1% of cases)

• Tissue injury (32.2%)
• Infection (17.1%)
• Chronic inflammatory disorders (11.7%)
• Iron deficiency anemia (11.1%) 2
• Post-splenectomy
• Malignancy
• Medications

Risk Stratification for Primary Thrombocytosis

High-Risk Patients

• Age ≥60 years OR
• History of previous thrombosis at any age

Intermediate-Risk Patients

• Age <60 years with no history of thrombosis BUT
• Platelet count >1,500 × 10⁹/L OR
• Significant cardiovascular risk factors

Low-Risk Patients

• Age <60 years
• No history of thrombosis
• No cardiovascular risk factors
• Platelet count <1,500 × 10⁹/L 3

Treatment Approach

Primary Thrombocytosis (Essential Thrombocythemia or Polycythemia Vera)

High-Risk Patients:

• Cytoreductive therapy with hydroxyurea as first-line treatment
• If hydroxyurea is not tolerated, consider anagrelide or interferon-alpha
• Low-dose aspirin (40-325 mg daily) if platelet count <1,500 × 10⁹/L 3
• Anagrelide is FDA-approved for treatment of thrombocythemia secondary to myeloproliferative neoplasms to reduce elevated platelet count and risk of thrombosis 4

Intermediate-Risk Patients:

• Treat cardiovascular risk factors
• Consider low-dose aspirin if platelet count <1,500 × 10⁹/L
• Observation or cytoreductive therapy (anagrelide, hydroxyurea, or interferon-alpha) based on individual risk assessment 3

Low-Risk Patients:

• Observation or low-dose aspirin 3

Secondary Thrombocytosis

• Treatment should target the underlying cause
• Observation is appropriate in most cases as platelet count normalizes with resolution of the underlying condition
• Aspirin may be considered in selected cases with cardiovascular risk factors
• Cytoreductive therapy is rarely indicated

Special Considerations

Extreme Thrombocytosis (>1,000 × 10⁹/L)

• Screen for acquired von Willebrand syndrome (AvWS) with ristocetin co-factor and multimer analysis
• If AvWS is present, avoid aspirin due to increased bleeding risk 5
• Consider cytoreductive therapy to reduce platelet count

Thrombocytosis with Thrombocytopenia Risk

• If chemotherapy-induced thrombocytopenia is anticipated:
  • Therapeutic anticoagulation may be administered if platelet count >50 × 10⁹/L
  • Half-dose anticoagulation for platelet counts 20-50 × 10⁹/L
  • Hold therapeutic anticoagulation if platelet count <20 × 10⁹/L 5

Pregnancy

• For pregnant women with ET or PV:
  • Low-dose aspirin is generally safe
  • For high-risk patients, interferon-alpha is preferred as it does not cross the placenta
  • Avoid hydroxyurea and anagrelide due to teratogenic potential 5

Monitoring

• Regular platelet count monitoring (frequency depends on etiology and treatment)
• For patients on cytoreductive therapy, monitor for side effects
• Assess for symptoms of thrombosis or bleeding
• Consider monitoring reticulated platelets in primary thrombocytosis, as increased platelet turnover (elevated reticulated platelet percentage) correlates with thrombotic risk 6

Common Pitfalls to Avoid

• Failing to distinguish between primary and secondary thrombocytosis
• Not screening for acquired von Willebrand syndrome in extreme thrombocytosis
• Inappropriate use of aspirin in patients with bleeding risk or extreme thrombocytosis
• Overlooking the underlying cause in secondary thrombocytosis
• Not recognizing that platelet function may be abnormal despite elevated counts
• Overtreatment of asymptomatic secondary thrombocytosis

The management approach should be tailored based on the underlying cause of thrombocytosis, with cytoreductive therapy reserved primarily for patients with primary thrombocytosis at high risk for thrombotic complications.