From the Guidelines
The workup for essential thrombocytosis (ET) should include a comprehensive approach to confirm the diagnosis and assess risk factors, with initial evaluation comprising a complete blood count, peripheral blood smear examination, and bone marrow biopsy with cytogenetic analysis, as recommended by the most recent guidelines 1. The initial evaluation should include:
- A complete blood count showing sustained platelet count >450,000/μL
- Peripheral blood smear examination
- Bone marrow biopsy with cytogenetic analysis, which is the preferred specimen for other MPNs, although peripheral blood may be used if there is peripheral involvement 1 Molecular testing for JAK2 V617F mutation, CALR mutations, and MPL mutations is essential, as these are driver mutations in ET, with the JAK2 V617F mutation found in 50-60% of cases, CALR mutations in 25-30%, and MPL mutations in 5-10% 1. Additional testing should include:
- Serum ferritin to exclude iron deficiency
- Inflammatory markers like CRP and ESR to rule out reactive thrombocytosis
- Screening for other myeloproliferative neoplasms, with the exclusion of BCR::ABL1 fusion required for the diagnosis of other MPNs and MDS/MPNs from CML 1 Risk stratification is crucial for treatment decisions, considering factors such as age >60 years, history of thrombosis, cardiovascular risk factors, and platelet count >1,500,000/μL, with the revised International Prognostic Score of Thrombosis for ET (IPSET-Thrombosis) preferred for risk stratification 1. Once diagnosed, patients should undergo:
- Cardiovascular risk assessment
- Screening for acquired von Willebrand syndrome if platelet counts exceed 1,000/μL This comprehensive workup allows for accurate diagnosis of ET according to WHO criteria and appropriate risk-adapted management, distinguishing it from reactive thrombocytosis and other myeloproliferative disorders, with treatment decisions guided by the most recent guidelines and evidence-based recommendations 1.
From the FDA Drug Label
A total of 942 patients with myeloproliferative neoplasms including 551 patients with Essential Thrombocythemia (ET) Patients were enrolled in clinical trials if their platelet count was ≥900,000/μL on two occasions or ≥650,000/μL on two occasions with documentation of symptoms associated with thrombocythemia The criteria for defining subjects as “responders” were reduction in platelets for at least 4 weeks to ≤600,000/μL, or by at least 50% from baseline value
The work up for essential thrombocytosis involves assessing the patient's platelet count, with a threshold of ≥900,000/μL on two occasions or ≥650,000/μL on two occasions with documentation of symptoms associated with thrombocythemia 2.
- Key criteria for evaluating response to treatment include a reduction in platelets for at least 4 weeks to ≤600,000/μL, or by at least 50% from baseline value. The FDA label does not provide a comprehensive workup for essential thrombocytosis, but it does provide information on the criteria used to enroll patients in clinical trials and evaluate their response to treatment.
From the Research
Diagnostic Criteria for Essential Thrombocytosis
- Essential thrombocytosis is characterized by clonal thrombocytosis, with a platelet count of ≥450 × 10^9/L 3
- The diagnosis requires the exclusion of other myeloid neoplasms, including prefibrotic myelofibrosis, polycythemia vera, chronic myeloid leukemia, and myelodysplastic syndromes with ring sideroblasts and thrombocytosis 3
- Bone marrow morphology typically shows an increased number of mature-appearing megakaryocytes distributed in loose clusters 3
Role of Bone Marrow Biopsy in Diagnosis
- Bone marrow biopsy is a valuable tool in the diagnosis of essential thrombocytosis, with histopathological criteria helping to differentiate it from reactive conditions and other myeloproliferative neoplasms 4
- However, there is substantial interobserver variability in the interpretation of bone marrow biopsy specimens, particularly for overall diagnosis and individual cellular characteristics such as megakaryocyte morphology 5
Clinical Features and Complications
- Essential thrombocytosis can present with thrombotic or hemorrhagic complications, microcirculatory symptoms, and less frequently, transformation into myelofibrosis or acute myeloid leukemia 3
- Cardiologists may encounter essential thrombocytosis in patients presenting with acute coronary syndrome, and should be aware of the disease and its treatment considerations 6
Treatment Considerations
- The main goal of therapy is to prevent thrombosis, with once-daily low-dose aspirin advised for all patients and twice daily for low-risk disease 3
- Cytoreductive therapy is advised for high-risk and optional for intermediate-risk disease, with first-line cytoreductive drugs of choice being hydroxyurea and pegylated interferon-α 3