From the Guidelines
Essential thrombocythemia (ET) management should prioritize cytoreduction with hydroxyurea as the first-line therapy for high-risk patients, in addition to low-dose aspirin for all patients with microvascular disturbances, as recommended by the most recent guidelines 1.
Essential Thrombocythemia Overview
Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm characterized by excessive platelet production, typically exceeding 450,000 platelets per microliter of blood. The management of ET focuses on preventing thrombotic complications while minimizing bleeding risks.
Risk Stratification and Management
- Low-risk patients (under 60 years with no history of thrombosis) can often be managed with low-dose aspirin (81-100 mg daily) alone.
- High-risk patients (over 60 years, history of thrombosis, or cardiovascular risk factors) require cytoreductive therapy in addition to aspirin.
First-Line Therapy
Hydroxyurea is the preferred first-line cytoreductive agent, usually started at 500-1000 mg daily and adjusted to maintain platelet counts below 400,000/μL, as supported by recent guidelines 1 and studies 1.
Alternative Treatments
Alternative treatments include interferon-alpha (particularly for younger patients or pregnant women), anagrelide (starting at 0.5 mg twice daily), and ruxolitinib for those resistant to other therapies.
Monitoring and Education
Regular monitoring of blood counts is essential, typically every 2-3 months once stable. Patients should be educated about symptoms of thrombosis or bleeding that require immediate medical attention.
Disease Mechanism
The disease mechanism involves acquired mutations (commonly in JAK2, CALR, or MPL genes) that lead to autonomous platelet production by megakaryocytes. While ET is generally associated with normal life expectancy, complications from thrombosis or progression to myelofibrosis or acute leukemia can occur, highlighting the importance of appropriate management 1.
From the FDA Drug Label
A total of 942 patients with myeloproliferative neoplasms including 551 patients with Essential Thrombocythemia (ET), 117 patients with Polycythemia Vera (PV), 178 patients with Chronic Myelogenous Leukemia (CML), and 96 patients with other myeloproliferative neoplasms (OMPN), were treated with anagrelide in three clinical trials 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 Efficacy was defined as reduction of platelet count to or near physiologic levels (150,000/μL to 400,000/μL). 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
Essential Thrombocythemia (ET) is a myeloproliferative neoplasm characterized by an elevated platelet count.
- The management of ET involves reducing the platelet count to or near physiologic levels (150,000/μL to 400,000/μL) using medications such as anagrelide.
- Patients with ET are typically treated with anagrelide starting at doses of 0.5 mg to 2.0 mg every 6 hours, with the dose increased if the platelet count is still high, but not to exceed 12 mg per day 2.
- The goal of treatment is to reduce the risk of thrombotic complications and improve symptoms associated with thrombocythemia.
- Anagrelide has been shown to be effective in reducing platelet counts in patients with ET, with response rates defined as a reduction in platelets for at least 4 weeks to ≤600,000/μL, or by at least 50% from baseline value 2.
From the Research
Essential Thrombocytopenia
- Essential thrombocytopenia is a clonal myeloproliferative neoplasm with excessive platelet production, associated with an increased risk of thrombosis and bleeding 3.
- The annual incidence rate of essential thrombocythemia in the US is 1.5/100 000 persons 3.
- Patients with essential thrombocythemia have a persistent platelet count of 450 × 109/L or greater 3.
Risk Factors
- Risk factors for thrombosis include age, prior thrombosis, and cardiovascular risk factors such as hypertension, diabetes mellitus, hyperlipidemias, and tobacco use 4, 3.
- The JAK2 gene variant is associated with an increased risk of venous thrombosis 3.
- Leukocytosis and JAK2V617F mutational status are also considered novel risk factors for cardiovascular events 5.
Management
- The management of essential thrombocythemia is based on a risk-oriented approach, with low-risk patients being observed or treated with low-dose aspirin, and high-risk patients being treated with hydroxyurea or other cytoreductive therapies 4, 5, 6.
- Low-dose aspirin (81-100 mg/d) is suggested for most patients with essential thrombocythemia to lower thrombosis risk 3.
- Cytoreductive therapy, such as hydroxyurea, is advised for high-risk and optional for intermediate-risk disease 6.
- Interferon alpha and anagrelide may be used as alternative therapies in selected patients 4, 5, 6.
Treatment Strategies
- The main goal of therapy is to prevent thrombosis, and treatment strategies may include low-dose aspirin, cytoreductive therapy, and management of cardiovascular risk factors 6.
- Specific treatment strategies are recommended for patients with extreme thrombocytosis, pregnancy, splanchnic vein thrombosis, perioperative care, and post-essential thrombocythemia myelofibrosis 6.
- New investigational drugs are being developed for the treatment of essential thrombocythemia 6.
Platelet-Leukocyte Interactions
- Platelet-leukocyte interactions may contribute to the pathogenesis of thrombosis in essential thrombocythemia 7.
- Low-dose aspirin has been shown to reduce platelet-leukocyte conjugates in patients with essential thrombocythemia, while hydroxyurea was found to be poorly effective in reducing these conjugates 7.