Does cytoreduction decrease the risk of thrombosis in essential thrombocythemia (ET)?

From the Guidelines

Cytoreduction does decrease the risk of thrombosis in essential thrombocythemia (ET). The most recent and highest quality study, published in 2018 1, supports the use of cytoreduction to reduce the risk of thrombosis in ET patients. According to this study, hydroxyurea is the first-line cytoreductive agent, and its use is recommended in combination with low-dose acetyl salicylic acid to prevent thrombotic complications.

Key Points

• Hydroxyurea is the first-line cytoreductive agent, typically started at 500-1000 mg daily and adjusted to maintain platelet counts below 400,000/μL while avoiding excessive myelosuppression.
• Interferon-alpha (particularly pegylated forms) is an alternative, especially for younger patients or those planning pregnancy.
• Anagrelide at 0.5 mg twice daily (increased gradually as needed) can be used as second-line therapy.
• Cytoreduction works by reducing the elevated platelet count characteristic of ET, which directly addresses the hypercoagulable state.
• Treatment should be combined with low-dose aspirin (81-100 mg daily) unless contraindicated, as supported by the 2011 study 1.
• Cytoreduction is particularly important for high-risk patients (those over 60 years old, with prior thrombosis, or with cardiovascular risk factors), as these individuals have the greatest thrombotic risk reduction with treatment, as noted in the 2018 study 1.

Management Considerations

• Regular blood count monitoring is essential to ensure therapeutic targets are maintained while avoiding excessive cytopenia.
• Patients should be managed aggressively for their cardiovascular risk factors and advised to stop smoking.
• The use of cytoreductive drugs in otherwise low-risk patients having well-controlled cardiovascular risk factors is not generally indicated, as stated in the 2011 study 1.
• Platelet count greater than 1,500 109/L is a risk factor for bleeding, and at this level of thrombocytosis, a platelet-lowering treatment should be considered, according to the 2018 study 1.

From the FDA Drug Label

Results from an observational study in patients with essential thrombocythemia suggest the rate of major hemorrhagic events (MHEs) in patients treated with anagrelide is higher than in those subjects treated with another cytoreductive treatment

The FDA drug label does not directly answer the question of whether cytoreduction decreases the risk of thrombosis in essential thrombocythemia (ET). However, it does provide information on the risks associated with anagrelide treatment, including bleeding events.

• Cytoreduction is mentioned as a treatment for essential thrombocythemia, but its effect on thrombosis risk is not directly addressed.
• The label discusses the risks of bleeding with anagrelide treatment, particularly when used with other medications that increase bleeding risk, such as aspirin 2. It is not possible to draw a conclusion about the effect of cytoreduction on thrombosis risk based on the provided information.

From the Research

Cytoreduction and Thrombosis Risk in Essential Thrombocythemia (ET)

• Cytoreductive therapy is used to prevent primary or tertiary thrombosis in ET patients, with high-thrombotic-risk patients and those with symptoms that may be ameliorated from cytoreductive therapy being candidates for this treatment 3.
• The use of cytoreductive agents such as hydroxyurea can reduce the rate of thrombotic events in ET patients, with a randomized trial showing that cytoreduction with hydroxyurea significantly lowered the risk of arterial or venous thrombotic events compared with no cytoreductive therapy 4.
• A risk-adapted strategy is recommended for the management of ET patients, with high-risk patients being treated with cytoreductive therapy and low-dose aspirin, while low-risk patients can be safely observed 5.
• Cytoreductive therapy has been shown to be effective in decreasing platelet number with negligible toxicity, although thrombocytosis control did not reduce the incidence of thrombosis in one study 6.
• Different cytoreductive drugs may have varying effects on platelet function and maturity in ET patients, with pegylated interferon alpha providing superior inhibition of platelet activation markers compared with hydroxycarbamide 7.

Factors Influencing Thrombosis Risk in ET

• Advanced age and a prior history of thrombosis are major predictors of thrombotic complications in ET patients 4, 5.
• The presence of cardiovascular risk factors such as hypertension, diabetes mellitus, and hyperlipidemias can increase the risk of thrombosis in ET patients 4.
• Genetic variants that upregulate the JAK-STAT signaling pathway, including Janus kinase 2 (JAK2), calreticulin (CALR), and myeloproliferative leukemia virus oncogene (MPL), can also increase the risk of thrombosis in ET patients 4.