What is the appropriate workup and management for a patient with elevated platelet count (thrombocytosis)?

Evaluation and Management of Thrombocytosis

For a patient with elevated platelet count, immediately distinguish primary from secondary thrombocytosis by obtaining a complete blood count with peripheral smear and JAK2 mutation testing, while simultaneously screening for the most common secondary causes: iron deficiency, inflammation, malignancy, and infection. 1

Initial Diagnostic Workup

Obtain these tests immediately:

• Complete blood count with peripheral smear to exclude pseudothrombocytosis (platelet clumping) and identify other cytopenias suggesting myeloproliferative neoplasm 1, 2
• JAK2 V617F mutation testing—present in the majority of primary thrombocytosis cases 1, 3
• Iron studies (ferritin, serum iron, TIBC) to detect iron deficiency, a common secondary cause 1, 4
• C-reactive protein or ESR to assess for inflammation 1, 4
• Review medication list and recent surgical history 4

If molecular markers are negative but clinical features suggest myeloproliferative neoplasm, proceed to bone marrow aspiration and biopsy. 2, 3 This is essential because neither JAK2 V617F nor MPL mutations are universally present in primary thrombocytosis. 3

Risk Stratification for Primary Thrombocytosis

Once primary thrombocytosis (essential thrombocythemia) is confirmed, stratify thrombotic risk:

High-risk patients (require cytoreductive therapy):

• Age ≥60 years, OR
• Prior thrombosis at any age 1

Low-risk patients (no cytoreductive therapy needed):

• Age <60 years AND
• No JAK2 mutation AND
• No prior thrombosis 1

Intermediate-risk patients require individualized assessment based on cardiovascular risk factors, platelet count trajectory, and presence of microvascular symptoms. 2

Treatment Algorithm

High-Risk Primary Thrombocytosis

First-line cytoreductive therapy: Hydroxyurea 1

Alternative agents for specific populations:

• Younger patients who wish to avoid hydroxyurea: Interferon alfa-2b or peginterferon alfa-2a/2b 1
• Pregnant patients requiring cytoreduction: Interferon alfa-2b or peginterferon alfa-2a/2b 1
• Patients who defer hydroxyurea: Interferon alfa-2b or peginterferon alfa-2a/2b 1

Antiplatelet Therapy

Low-dose aspirin (81-100 mg daily) can be added for vascular symptoms (headache, paresthesias, visual disturbances, erythromelalgia) when platelet count is <1,500 × 10⁹/L. 1, 5 Above this threshold, acquired von Willebrand syndrome may develop, paradoxically increasing bleeding risk. 3

Low-Risk Primary Thrombocytosis

Observation without cytoreductive therapy if asymptomatic. 1 Consider low-dose aspirin for microvascular symptoms if platelet count <1,500 × 10⁹/L. 1

Secondary (Reactive) Thrombocytosis

No specific treatment for the elevated platelet count itself—address the underlying cause. 4, 6 Secondary thrombocytosis carries minimal thrombotic risk compared to primary thrombocytosis (7.9% vs 17.1% complication rate in extreme thrombocytosis). 7

Perioperative Management

For surgical patients with thrombocytosis and normal platelet function:

• Platelet count >100 × 10⁹/L: Platelet transfusion rarely indicated 1
• Platelet count 50-100 × 10⁹/L: Individualized assessment based on bleeding risk and procedure type 1
• Platelet count <50 × 10⁹/L: Platelet transfusion usually indicated in presence of excessive bleeding 1

In primary thrombocytosis, the elevated count itself increases surgical thrombotic risk—ensure adequate cytoreduction before elective procedures. 3, 5

Neurologic Complications

Thrombocytosis-related neurologic symptoms include headache, paresthesias, transient ischemic attacks, visual disturbances, and seizures. 5 These occur predominantly in primary thrombocytosis and respond to:

• Plateletpheresis for acute major thrombo-hemorrhagic events 5
• Cytoreductive therapy (hydroxyurea, interferon) for sustained control 5
• Antiplatelet agents for minor microvascular symptoms 5

Critical Pitfalls

Do not assume all thrombocytosis is benign reactive thrombocytosis. Primary thrombocytosis requires specific treatment to prevent thrombotic complications. 4, 3

Do not use aspirin when platelet count exceeds 1,500 × 10⁹/L due to acquired von Willebrand syndrome and paradoxical bleeding risk. 3

Do not delay cytoreductive therapy in high-risk patients (age ≥60 or prior thrombosis), as thrombotic events are the predominant cause of morbidity and mortality. 1, 3

In extreme thrombocytosis (>1,000 × 10⁹/L), two-thirds of cases are secondary, but one-third represent myeloproliferative disorders requiring specific therapy. 7 Always complete the diagnostic workup rather than assuming a reactive cause.