Essential Thrombocytosis Treatment & Management

Updated: Aug 22, 2019
  • Author: Asheesh Lal, MBBS, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Treatment

Medical Care

Treatment in patients with essential thrombocytosis (primary thrombocythemia) should be individualized on the basis of risk factors for thrombosis or bleeding. 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
  • Obesity
  • Cardiovascular risk factors such as smoking, hypertension, and hypercholesterolemia
  • Markers of hypercoagulability such as factor V Leiden and antiphospholipid antibodies [5]
  • JAK2 or MPL mutation

Observation may be appropriate for very-low-risk patients (ie, those lacking any of the above risk factors), although once-daily aspirin may be used in those with cardiovascular risk factors. [29] Generally, surgery or pregnancy is not associated with significantly increased thrombohemorrhagic risk in low-risk patients.

Low-risk patients (ie, those whose only risk factor is JAK2 or MPL mutation) can be treated with daily low-dose (100 mg) aspirin therapy; low-dose aspirin can be given twice daily, especially in patients with both of those risk factors. [29]  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. In emergencies, plateletpheresis may be useful to achieve a rapid decrease in platelet counts. Plateletpheresis may be indicated 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

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.

Hydroxyurea is generally considered the first-line drug for cytoreductive therapy in essential thrombocytosis. [1, 30, 31, 32] Second-line agents include the following [32, 1] :

  • Busulfan
  • Anagrelide [31, 33]
  • Interferon alfa
  • Ruxolitinib

 A combination of cytoreductive agents may be needed in cases difficult to manage by single-agent therapy.

A European study in 382 patients concluded that cytoreductive therapy should not be used in patients with essential thrombocytosis who are age 40 to 59 years and lack high-risk factors. After a median follow-up of 73 months, vascular events, myelofibrotic transformation, or leukemic transformation were not significantly different in patients who received hydroxyurea plus aspirin than in those receiving aspirin only. [34]

Interferon alfa produces high rates of clinical and molecular responses in patients with JAK2 or CALR mutations. [35, 36] 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. [37] Interferon alfa may also be used as second-line therapy in older patients. [38]

Ruxolitinib is a JAK1/JAK2 inhibitor that is approved for use in myelofibrosis and polycythemia vera, and some benefit has been reported in patients with essential thrombocytosis. [39] However, results of a randomized phase II trial of ruxolitinib versus best available therapy in patients with essential thrombocytosis or polycythemia vera who were resistant or intolerant to hydroxyurea suggest that ruxolitinib is not superior to current second-line treatments. [40]

In that trial, Harrison et al reported no evidence of improvement in complete response within 1 year in 27 of 58 patients treated with ruxolitinib versus 23 of 52 treated with best available therapy (46.6% versus 44.2%, respectively; P= 0.40). At 2 years, some disease-related symptoms had improved in patients receiving ruxolitinib relative to best available treatment, but rates of thrombosis, hemorrhage, and transformation were not significantly different, and molecular responses were uncommon. [40]

Another JAK inhibitor, fedratinib, is indicated for adults with intermediate-2 or high-risk post–essential thrombocythemia myelofibrosis. Fedratinib is a selective JAK2 inhibitor. [44]

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. [41]

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Surgical Care

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.

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Consultations

A hematologist can help manage patients with essential thrombocytosis as well as monitor the cytoreductive therapy.

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