What is the appropriate workup for thrombocytosis (elevated platelet count)?

From the Guidelines

The workup for thrombocytosis should begin with a complete blood count with differential to confirm the elevated platelet count (>450,000/μL) and assess for other hematologic abnormalities, as recommended by recent guidelines 1. Initial evaluation should distinguish between primary (clonal) and secondary (reactive) thrombocytosis.

• Essential laboratory tests include:
  • Iron studies (ferritin, iron, TIBC) to rule out iron deficiency
  • Inflammatory markers (ESR, CRP) to assess for underlying inflammation
  • Peripheral blood smear to evaluate for morphological abnormalities
  • JAK2 V617F mutation testing to identify primary thrombocytosis If primary thrombocytosis is suspected,
• Bone marrow biopsy with cytogenetic analysis and molecular testing for mutations in JAK2, CALR, and MPL genes should be performed to diagnose myeloproliferative neoplasms like essential thrombocytosis 1. For secondary causes,
• Focus on identifying underlying conditions such as iron deficiency, infection, inflammation, malignancy, or recent splenectomy. Abdominal imaging may be warranted to assess spleen size. Management depends on the underlying cause - treating the primary condition for secondary thrombocytosis or implementing cytoreductive therapy and/or antiplatelet agents for primary thrombocytosis based on risk stratification, with consideration of advanced age and history of thrombosis as key risk factors 1. A risk-adapted therapeutic strategy should be implemented, taking into account the presence of cardiovascular risk factors, JAK2 mutation status, and extreme thrombocytosis, as outlined in recent guidelines 1.

From the Research

Thrombocytosis Workup

Thrombocytosis is a condition characterized by an elevated platelet count, which can be caused by various physiological and pathological mechanisms. The workup for thrombocytosis involves distinguishing between reactive or secondary thrombocytosis and thrombocytosis associated with an underlying myeloproliferative neoplasm.

Diagnostic Approach

• The investigation of suspected primary thrombocytosis includes testing for disease-associated mutations, such as JAK2, CALR, and MPL mutations 2, 3, 4.
• Bone marrow morphology typically shows an increased number of mature-appearing megakaryocytes distributed in loose clusters 3, 4.
• The exclusion of other myeloid neoplasms, including prefibrotic myelofibrosis, polycythemia vera, chronic myeloid leukemia, and myelodysplastic syndromes with ring sideroblasts and thrombocytosis, is essential for the diagnosis of essential thrombocythemia 3, 4.

Risk Stratification

• The risk of thrombotic complications is higher in patients with JAK2 mutation 3, 4.
• The triple A survival risk model, based on Age, Absolute neutrophil count, and Absolute lymphocyte count, effectively delineates high-, intermediate-1-, intermediate-2-, and low-risk disease 3.
• Four risk categories are considered: very low, low, intermediate, and high, with corresponding median survivals of 47,21,14, and 8 years, respectively 3.

Management

• The main goal of therapy is to prevent thrombosis 3, 4, 5.
• Once-daily low-dose aspirin is advised for all patients, and cytoreductive therapy is recommended for high-risk patients 3, 4.
• First-line cytoreductive drugs of choice are hydroxyurea and pegylated interferon-α, and second-line drugs of choice are busulfan 3, 4.

Note: Study 6 is not relevant to the topic of thrombocytosis workup.