What is the appropriate workup and management for a patient with thrombocytosis (elevated platelet count) and a platelet count of 600?

Workup of Thrombocytosis with Platelet Count of 600,000/μL

Immediate Diagnostic Classification

The first step is to distinguish between primary (clonal myeloproliferative neoplasm) and secondary (reactive) thrombocytosis, as primary thrombocytosis carries significantly higher thrombotic risk and requires different management. 1, 2

Initial Laboratory Workup

• Complete blood count with differential to assess for leukocytosis, elevated hematocrit (suggesting polycythemia vera), or other cytopenias 1, 2
• Peripheral blood smear to evaluate for abnormal cell morphology, immature cells, or features of myeloproliferative disorders 1
• JAK2 V617F mutation testing is essential, as 86% of primary thrombocytosis cases have at least one molecular marker (JAK2, CALR, or MPL mutations) 2, 1
• CALR and MPL mutation testing if JAK2 is negative and primary thrombocytosis is still suspected 1
• Inflammatory markers (CRP, ESR) to screen for chronic inflammatory conditions 2, 3
• Iron studies (ferritin, serum iron, TIBC) as iron deficiency anemia accounts for 11% of secondary thrombocytosis 2, 4

Clinical Assessment for Secondary Causes

• Evaluate for tissue injury or recent surgery, which accounts for 32% of secondary thrombocytosis 2
• Screen for active infection, responsible for 17-24% of cases 2, 3
• Assess for chronic inflammatory disorders (inflammatory bowel disease, rheumatoid arthritis, vasculitis), accounting for 10-12% of cases 2, 3
• Screen for occult malignancy based on age-appropriate cancer screening, as malignancy causes 13% of secondary thrombocytosis 3, 4
• Evaluate for functional or surgical asplenia 4

Risk Stratification if Primary Thrombocytosis Confirmed

If molecular markers are positive, immediate risk stratification determines treatment intensity. 1

High-Risk Features Requiring Cytoreductive Therapy

• Age >60 years 1
• History of prior thrombosis (arterial or venous) 1, 3
• JAK2 V617F mutation presence increases thrombotic risk in essential thrombocythemia 1

Thrombotic Risk Assessment

• Primary thrombocytosis has significantly higher incidence of both arterial and venous thromboembolism compared to secondary thrombocytosis 2, 3
• Secondary thrombocytosis rarely causes thrombotic complications unless additional risk factors are present, and venous events predominate 3

Additional Testing for Extreme Thrombocytosis

• If platelet count exceeds 1,000/μL, screen for acquired von Willebrand syndrome with ristocetin cofactor activity and multimer analysis, as this paradoxically increases bleeding risk 1, 4
• Immediate hematology referral is indicated for platelet counts >1,000/μL regardless of etiology 1

Management Algorithm Based on Classification

For Primary Thrombocytosis (High-Risk)

• Initiate cytoreductive therapy with hydroxyurea targeting platelet count <400,000/μL 1, 4
• Add low-dose aspirin 81-100 mg daily unless contraindicated by acquired von Willebrand syndrome or active bleeding 1, 4
• Peginterferon alfa-2a is an alternative to hydroxyurea, achieving 76% complete hematologic response 1

For Primary Thrombocytosis (Low-Risk)

• For JAK2-mutated patients: Consider low-dose aspirin 81-100 mg daily 1
• For JAK2-unmutated patients: Observation alone is reasonable, avoid aspirin in extreme thrombocytosis without ruling out acquired von Willebrand syndrome 1
• Initiate cytoreductive therapy if symptomatic thrombocytosis, progressive leukocytosis, or disease-related symptoms develop 1

For Secondary Thrombocytosis

• Treat the underlying cause rather than the platelet count itself 4
• Cytoreductive therapy is generally not indicated unless platelet count exceeds 1,500,000/μL 4
• Antiplatelet therapy is not routinely recommended without other thrombotic risk factors 4
• At platelet count of 600,000/μL from secondary causes, no specific platelet-directed therapy is needed 4, 3

Critical Pitfalls to Avoid

• Do not assume secondary thrombocytosis is benign without excluding primary thrombocytosis, as 12-13% of thrombocytosis cases are primary with significantly higher thrombotic risk 2, 3
• Do not delay JAK2 mutation testing, as molecular markers are present in 86% of primary cases and simplify diagnosis 2
• Do not give aspirin in extreme thrombocytosis (>1,000/μL) without first ruling out acquired von Willebrand syndrome, as this paradoxically increases bleeding risk 1
• Do not treat secondary thrombocytosis with cytoreductive agents or antiplatelet therapy unless specific indications exist beyond the platelet count 4, 3

Monitoring Strategy

• For primary thrombocytosis on cytoreductive therapy: Regular CBC monitoring to assess response with target platelet count <400,000/μL 1
• Monitor for myelosuppression with hydroxyurea therapy 1
• For secondary thrombocytosis: Monitor underlying condition; platelet count typically normalizes when primary condition resolves 4