Essential Thrombocytosis Treatment & Management
- Author: Asheesh Lal, MBBS, MD; Chief Editor: Emmanuel C Besa, MD more...
Treatment in patients with essential thrombocytosis (primary thrombocythemia) should be individualized on the basis of risk factors for thrombohemorrhagic complications. Risk factors include the following:
Age 60 years or older
History of thrombosis
Platelet count greater than 1500 x 10 9/L (1.5 million/µL), which is paradoxically associated with an increased risk of gastrointestinal tract bleeding in young women
Cardiovascular risk factors such as smoking, hypertension, and hypercholesterolemia
Markers of hypercoagulability such as factor V Leiden and antiphospholipid antibodies 
Observation may be appropriate for low-risk patients (ie, those lacking any of the above risk factors). Low-risk patients experience lower rates of thrombosis or bleeding. Generally, significantly increased thrombohemorrhagic risk is not associated with surgery or pregnancy in low-risk patients. Alternatively, low-risk patients may be treated with low-dose aspirin. In addition, low-dose aspirin may be useful in treating patients with symptoms of microvascular occlusion (eg, erythromelalgia).
In emergencies, plateletpheresis may be useful to achieve a rapid decrease in platelet counts in the setting of acute thrombosis and/or marked thrombocytosis.
Cytoreductive therapy should be used to decrease the platelet count in high-risk patients (eg, those over 60 years of age, those with a history of thrombosis, or platelet counts greater than 1.5 million/µL). Low-dose aspirin with cytoreductive therapy or observation may help treat intermediate-risk patients (ie, those who do not fit into either high-risk or low-risk groups).
Lifestyle modifications should be recommended for all patients with reversible risk factors. These include diet and exercise to promote weight loss for obese patients and smoking cessation for smokers.
Cytoreductive therapy is used to reduce the risk of hemorrhage for patients with platelet counts above 1 million/μL. Extreme thrombocytosis may promote the abnormal adsorption of large von Willebrand factor (VWF) multimers. These patients should be screened for the presence of acquired von Willebrand disease (VWD). Low-dose aspirin therapy (eg, ≤100 mg/day) is acceptable if the ristocetin cofactor level is at least 30% in absence of other high risk factors; if it is less than 30%, all aspirin should be avoided.
Cytoreductive drugs that are commonly used for essential thrombocytosis include the following:
A randomized study comparing hydroxyurea versus observation in patients at high risk for thrombosis showed a marked decrease in the number of thrombotic episodes in the hydroxyurea arm. Another randomized study that compared hydroxyurea plus aspirin with anagrelide plus aspirin found that in high-risk patients (previous thrombosis, age >60 y or platelets >1000 x 109/L), treatment with anagrelide plus aspirin was associated with increased rates of arterial thrombosis, major hemorrhage, and myelofibrotic transformation, but a decreased rate of venous thromboembolism.
The reason for the higher rate of myelofibrosis in patients receiving anagrelide remains unclear. This finding may be the result of increased production of profibrotic cytokines with anagrelide, or may simply represent the natural course of essential thrombocytosis.
In view of those studies, hydroxyurea should be considered as cytoreductive agent of choice for most high-risk patients with essential thrombocytosis. Further choice of the cytoreductive agent should also be based on patient factors (eg, age, child-bearing potential, cost, life expectancy, comorbidities). A combination of cytoreductive agents may be needed in cases difficult to manage by single-agent therapy.
Interferon alfa produces high rates of clinical and molecular responses in patients with JAK2 or CALR mutations.[28, 29] Italian guidelines recommend interferon alfa as a first-line platelet-lowering therapy for patients younger than 40 years, male or female, who have no childbearing potential. Interferon alfa may also be used as second-line therapy in older patients.
In emergencies, plateletpheresis may be useful to achieve a rapid decrease in platelet counts. Plateletphersis may be indicated in the setting of acute thrombosis and/or marked thrombocytosis.
The investigational drug imetelstat, a telomerase inhibitor, has shown promise in the treatment of essential thrombocytosis. In a phase II trial that included18 patients in whom prior treatments had been ineffective or had caused unacceptable side effects from, all 18 had hematologic responses, and 16 patients had a complete hematologic response; most patients also demonstrated a molecular response.
Patients with essential thrombocytosis (primary thrombocythemia) undergoing surgery are at increased risk for bleeding and thrombosis. Administer cytoreductive therapy to decrease the platelet count to the reference range before surgery. Avoid splenectomy because it can markedly increase the platelet count and the risk of both hemorrhagic and thrombotic events.
A hematologist can help manage patients with essential thrombocytosis as well as monitor the cytoreductive therapy.
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