Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

life-threatening thrombosis, severe thrombocytosis-related neurologic complications, or severe bleeding

1st line – plateletpheresis

Back
ACUTE
|
life-threatening thrombosis, severe thrombocytosis-related neurologic complications, or severe bleeding
1st line – 

plateletpheresis

Plateletpheresis is rarely used in treating essential thrombocythemia (ET), but may be considered in certain emergency situations (e.g., life-threatening thrombosis, severe thrombocytosis-related neurologic complications, or severe bleeding).[37][58]​ It may help rapidly reduce the platelet count and relieve acute symptoms associated with ET.[59]​​

Plateletpheresis involves removing whole blood from a patient, separating the blood into its components, removing the platelets, and then returning the remaining blood components to the patient.

ONGOING

nonpregnant: very low-, low-, or intermediate-risk

1st line – observation or antiplatelet therapy

Back
ONGOING
|
nonpregnant: very low-, low-, or intermediate-risk
1st line – 

observation or antiplatelet therapy

Treatment for essential thrombocythemia (ET) should be individualized (e.g., based on age, risk for thrombosis, mutation status, presence of symptoms).​​[37][44]

The goals of treatment are to reduce the risk of thrombosis and bleeding complications, manage symptoms, and reduce the risk of progression (e.g., to myelofibrosis or leukemia).​​[44]​​​​​ Currently, there are no curative treatments for ET.

The International Prognostic Score of Thrombosis for Essential Thrombocythemia (IPSET-thrombosis) tool can be used to stratify patients into four risk groups to guide treatment.[37][38][42][43]​

​​very low-risk: age ≤60 years, no thrombosis history, no JAK2 V617F mutation;

low-risk: age ≤60 years, no thrombosis history, with JAK2 V617F mutation;

intermediate-risk: age >60 years, no thrombosis history, no JAK2 V617F mutation;

high-risk: thrombosis history at any age, or age >60 years with JAK2 V617F mutation.​​​

Very low-risk patients who are asymptomatic do not require treatment; observation is appropriate.​​[37][38]​​​​[44]​​​​​​​​ These patients may receive low-dose (once-daily) aspirin if they have vascular symptoms (e.g., headaches, chest pain, and erythromelalgia).​​[37][44]

Low-risk patients and intermediate-risk patients should receive low-dose (once-daily) aspirin, although observation may be an option for some low-risk patients. Clopidogrel may be considered for patients with major contraindications to aspirin (e.g., allergy or peptic ulcer disease).

Higher doses of aspirin may be appropriate in selected patients (e.g., with cardiovascular risk factors), as clinically indicated. For patients with aspirin-resistant symptoms, a twice-daily regimen of low-dose aspirin, or alternatively clopidogrel (alone or in combination with aspirin), may be considered, with close monitoring. The increased risk of bleeding with higher or more frequent doses of aspirin must be carefully weighed against the potential benefit (e.g., reduction in the presence and/or severity of vasomotor symptoms, including headache).​[37][46]​​

Aspirin should be used with caution and monitored closely in patients with acquired von Willebrand disease because of increased risk of bleeding.

Antiplatelet agents are typically stopped 7 to 10 days before major surgery, or surgery to critical sites, and reintroduced as soon as feasible with surgeon input (typically 24 hours after surgery).​[37]

Postoperative thromboprophylaxis is recommended according to usual guidelines for the specific procedure.

Primary options

aspirin: 81-100 mg orally once or twice daily

Secondary options

clopidogrel: 75 mg orally once daily

OR

clopidogrel: 75 mg orally once daily

and

aspirin: 81-100 mg orally once or twice daily

Plus – lifestyle modification + supportive care + regular monitoring

Back
ONGOING
|
nonpregnant: very low-, low-, or intermediate-risk
Plus – 

lifestyle modification + supportive care + regular monitoring

Treatment recommended for ALL patients in selected patient group

Cardiovascular risk factors (e.g., hypertension, hyperlipidemia, diabetes, smoking) should be identified and managed in all patients with essential thrombocythemia.​[37]​

Give advice on lifestyle modification (e.g., smoking cessation, weight control) to reduce the risk of developing symptoms, or to moderate the severity of existing symptoms.[45]​

Offer supportive care to ensure optimum symptom management.

Monitor platelets regularly in all patients (including asymptomatic patients and those in a steady state after starting treatment).

Monitor for new thrombosis, acquired von Willebrand disease, and/or disease-related major bleeding.

Consider – cytoreductive therapy

Back
ONGOING
|
nonpregnant: very low-, low-, or intermediate-risk
Consider – 

cytoreductive therapy

Treatment recommended for SOME patients in selected patient group

Very low-risk, low-risk, or intermediate-risk patients should be reviewed as clinically indicated to monitor for signs and symptoms of disease progression and to evaluate for indications of cytoreductive therapy.[37]​

Indications for cytoreductive therapy in symptomatic patients include:[37][47]​​

new thrombosis, acquired von Willebrand disease, and/or disease-related major bleeding;

splenomegaly;

progressive thrombocytosis and/or leukocytosis;

disease-related symptoms (e.g., pruritus, night sweats, fatigue); and

vascular symptoms (e.g., headaches, chest pain, and erythromelalgia) not responsive to aspirin (or other antiplatelet therapy).​

Patients who are symptomatic and have indications for cytoreductive therapy should be treated with a cytoreductive agent (in addition to antiplatelet therapy).

​Bone marrow aspirate and biopsy should be performed to rule out disease progression to myelofibrosis prior to the initiation of cytoreductive therapy.[37]

Hydroxyurea is the preferred cytoreductive agent in most patients.[44][45][48]​​​​​​​​ Doses are titrated up or down, balancing the desired effect on platelet count while minimizing neutropenia and anemia. Evidence-based guidelines regarding target platelet count are lacking; in low-risk essential thrombocythemia (ET) it should be the level at which symptom relief is observed.[38]​​

Hydroxyurea should be used with caution as it is teratogenic and potentially leukemogenic.[49]​​ It is relatively contraindicated in pregnancy, in women of childbearing potential, and in women who are breast-feeding. 

The following agents are alternatives to hydroxyurea.[37][38]​​​

Peginterferon alfa-2a: effective for treating patients with Janus kinase 2 (JAK2)-mutated ET or calreticulin (CALR)-mutated ET.[50][51]​​​​​ Peginterferon alfa-2a may be preferred to hydroxyurea in younger patients, particularly women of childbearing age and pregnant patients, because it is non-teratogenic and non-leukemogenic.[52]

Busulfan: typically used as a second-line option (after hydroxyurea) in older patients (i.e., ages ≥65 years).[38]​​[53]​​​ Busulfan may be associated with a significant rate of transformation to acute myeloid leukemia, although the leukemogenicity of busulfan is debated.[38]​ Sequential use of busulfan and hydroxyurea has been reported to significantly increase the risk of second malignancies.[54]​ The National Comprehensive Cancer Network (NCCN) guidelines do not recommend the use of busulfan for ET.[37]​

Anagrelide: can be considered for second-line use after failure of other cytoreductive agents (e.g., hydroxyurea, peginterferon alfa-2a). Careful evaluation is recommended before starting treatment because of the risk of adverse effects (e.g., cardiotoxicity), especially in older patients.[37][48][52]​ Some studies suggest that anagrelide may increase the risk of progression to myelofibrosis and decrease survival.[38][48][55]​​​

For patients receiving cytoreductive therapy who are undergoing elective surgery, the blood count is optimized preoperatively, and interruptions in therapy should be kept to a minimum.[64]

Postoperative thromboprophylaxis is recommended according to usual guidelines for the specific procedure.

Primary options

hydroxyurea: consult specialist for guidance on dose

Secondary options

peginterferon alfa 2a: consult specialist for guidance on dose

Tertiary options

busulfan: consult specialist for guidance on dose

OR

anagrelide: consult specialist for guidance on dose

nonpregnant: high risk

1st line – antiplatelet therapy

Back
ONGOING
|
nonpregnant: high risk
1st line – 

antiplatelet therapy

Treatment for essential thrombocythemia (ET) should be individualized (e.g., based on age, risk for thrombosis, mutation status, presence of symptoms).​​[37][44]

The goals of treatment are to reduce the risk of thrombosis and bleeding complications, manage symptoms, and reduce the risk of progression (e.g., to myelofibrosis or leukemia).​​[44]​​​​​ Currently, there are no curative treatments for ET.

The International Prognostic Score of Thrombosis for Essential Thrombocythemia (IPSET-thrombosis) tool can be used to stratify patients into four risk groups to guide treatment.[37][38][42][43]​ ​​

very low-risk: age ≤60 years, no thrombosis history, no JAK2 V617F mutation;

low-risk: age ≤60 years, no thrombosis history, with JAK2 V617F mutation;

intermediate-risk: age >60 years, no thrombosis history, no JAK2 V617F mutation;

high-risk: thrombosis history at any age, or age >60 years with JAK2 V617F mutation.​​​

High-risk patients should receive low-dose (once-daily) aspirin and cytoreductive therapy as initial treatment.​​[37][38]​​​​​​[44] Clopidogrel may be an option for patients with major contraindications to aspirin (e.g., allergy or peptic ulcer disease).​

For patients with aspirin-resistant symptoms, a twice-daily regimen of low-dose aspirin or, alternatively clopidogrel (alone or in combination with aspirin), may be considered, with close monitoring.

A twice-daily regimen of low-dose aspirin may be considered for high-risk patients with a history of arterial thrombosis or with cardiovascular risk factors.[38][46]

The increased risk of bleeding with higher or more frequent doses of aspirin must be carefully weighed against the potential benefit (e.g., reduction in the presence and/or severity of vasomotor symptoms, including headache).​[37][46]​​

Aspirin should be used with caution and monitored closely in patients with acquired von Willebrand disease because of increased risk of bleeding.

Antiplatelet agents are typically stopped 7 to 10 days before major surgery, or surgery to critical sites, and reintroduced as soon as feasible with surgeon input (typically 24 hours after surgery).​[37]

Postoperative thromboprophylaxis is recommended according to usual guidelines for the specific procedure.

Primary options

aspirin: 81-100 mg orally once or twice daily

Secondary options

clopidogrel: 75 mg orally once daily

OR

clopidogrel: 75 mg orally once daily

and

aspirin: 81-100 mg orally once or twice daily

Plus – cytoreductive therapy

Back
ONGOING
|
nonpregnant: high risk
Plus – 

cytoreductive therapy

Treatment recommended for ALL patients in selected patient group

High-risk patients should receive low-dose (once-daily) aspirin and cytoreductive therapy as initial treatment.​​[37][38]​​​​​​​[44]

The management goal is to adequately control myeloproliferation and keep platelet and leukocyte counts in the normal range (platelet count 150,000 to 400,000/microliter; leukocyte count: 4500 to 10,000/microliter), without significant clinical toxicity or suppression of other marrow elements.[57]

Hydroxyurea is the preferred cytoreductive agent in most patients.[37][44]​​​​[48]​​​​​ Doses are titrated up or down, balancing the desired effect on platelet count while minimizing neutropenia and anemia.

Hydroxyurea should be used with caution as it is teratogenic and potentially leukemogenic.[49]​​ It is relatively contraindicated in pregnancy, in women with childbearing potential, and in women who are breast-feeding.

Peginterferon alfa-2a may be considered as an alternative option for younger patients (age <65 years), or for those who do not wish to start hydroxyurea.[37] It may be preferred to hydroxyurea in women of childbearing age and pregnant patients, because it is non-teratogenic and non-leukemogenic.[52] Peginterferon alfa-2a is effective for treating patients with JAK2-mutated essential thrombocythemia (ET) or calreticulin (CALR)-mutated ET.[50][51]

In high-risk patients experiencing intolerance or resistance to first-line therapy, anagrelide or busulfan may be considered as second-line agents.[56] The NCCN guidelines do not recommend the use of busulfan for ET.[37]​​​​​

Anagrelide can be considered for second-line use after failure of other cytoreductive agents (e.g., hydroxyurea, peginterferon alfa-2a). Careful evaluation is recommended before starting treatment because of the risk of adverse effects (e.g., cardiotoxicity), especially in older patients.[37][48][52]​ Some studies suggest that anagrelide may increase the risk of progression to myelofibrosis and decrease survival.[38][48][55]​​​​

Busulfan is typically used as a second-line option (after hydroxyurea) in older patients (i.e., those ages ≥65 years).[38][53]​​ Busulfan may be associated with a significant rate of transformation to acute myeloid leukemia, although the leukemogenicity of busulfan is debated.[38] Sequential use of busulfan and hydroxyurea has been reported to significantly increase the risk of second malignancies.[54]​​​

Potential indications for a change of cytoreductive therapy include: intolerance or resistance to first-line cytoreductive therapy; new thrombosis, acquired von Willebrand syndrome, or disease-related major bleeding; leukocytosis; thrombocytosis; splenomegaly; disease-related symptoms (e.g., pruritus, night sweats, and fatigue); vascular symptoms (e.g., headaches, chest pain, and erythromelalgia) not responsive to aspirin.[37]

Patients should be reviewed as clinically indicated to monitor for signs and symptoms of disease progression.[37]​​​​ If the response to treatment is adequate, it should be continued. If the response is inadequate or there is a loss of response, an alternative cytoreductive agent should be tried. If there is clinical or laboratory-based suspicion of progression to myelofibrosis, perform bone marrow aspirate and and biopsy.[37]

For patients receiving cytoreductive therapy who are undergoing elective surgery, the blood count is optimized preoperatively, and interruptions in therapy should be kept to a minimum.[64] Postoperative thromboprophylaxis is recommended according to usual guidelines for the specific procedure.​

Primary options

hydroxyurea: consult specialist for guidance on dose

OR

peginterferon alfa 2a: consult specialist for guidance on dose

Secondary options

anagrelide: consult specialist for guidance on dose

OR

busulfan: consult specialist for guidance on dose

Plus – lifestyle modification + supportive care + regular monitoring

Back
ONGOING
|
nonpregnant: high risk
Plus – 

lifestyle modification + supportive care + regular monitoring

Treatment recommended for ALL patients in selected patient group

Cardiovascular risk factors (e.g., hypertension, hyperlipidemia, diabetes, smoking) should be identified and managed in all patients with essential thrombocythemia.​[37]​

Give advice on lifestyle modification (e.g., smoking cessation, weight control) to reduce the risk of developing symptoms, or to moderate the severity of existing symptoms.[45]​

Offer supportive care to ensure optimum symptom management.

Monitor platelets regularly in all patients (including asymptomatic patients and those in a steady state after starting treatment).

Monitor for new thrombosis, acquired von Willebrand disease, and/or disease-related major bleeding.

Consider – anticoagulation

Back
ONGOING
|
nonpregnant: high risk
Consider – 

anticoagulation

Treatment recommended for SOME patients in selected patient group

Systemic anticoagulation (combined with aspirin and cytoreductive therapy) may be considered for high-risk patients with a history of venous thrombosis.[38]​​

Use of systemic anticoagulation in high-risk patients should be individualized, balancing bleeding risk and benefits.

Primary options

heparin: consult specialist for guidance on dose

OR

enoxaparin: consult specialist for guidance on dose

OR

warfarin: 2-5 mg orally once daily initially, adjust according to INR

More

pregnant: very low-, low-, or intermediate-risk

1st line – antiplatelet therapy

Back
ONGOING
|
pregnant: very low-, low-, or intermediate-risk
1st line – 

antiplatelet therapy

Treating women with essential thrombocythemia (ET) during pregnancy is challenging due to the increased risk for first trimester spontaneous abortion, and thrombotic and obstetric complications.[10] Patients who become pregnant should be under the joint care of a hematologist and an obstetrician experienced in high-risk care.​

Very low-, low-, or intermediate-risk patients who are pregnant should receive low-dose (once-daily) aspirin as initial therapy to reduce the risk of placental thrombosis, spontaneous abortion, and other complications (e.g., preeclampsia).[10]

Aspirin has been reported to be effective in reducing pregnancy complications, especially in patients with Janus kinase 2 (JAK2)-mutated ET.[60]​ One systematic review reported a higher live birth rate among women with myeloproliferative neoplasms who were treated with aspirin alone or in combination with interferon.[61]

Aspirin should be used with caution and monitored closely in patients with acquired von Willebrand disease because of increased risk of bleeding.

Clopidogrel can be considered for pregnant patients if aspirin is contraindicated (e.g., due to allergy or peptic ulcer disease).

Primary options

aspirin: 81-100 mg orally once daily

Secondary options

clopidogrel: 75 mg orally once daily

Plus – lifestyle modification + supportive care + regular monitoring

Back
ONGOING
|
pregnant: very low-, low-, or intermediate-risk
Plus – 

lifestyle modification + supportive care + regular monitoring

Treatment recommended for ALL patients in selected patient group

Cardiovascular risk factors (e.g., hypertension, hyperlipidemia, diabetes, smoking) should be identified and managed in all patients with essential thrombocythemia.​[37]​

Give advice on lifestyle modification (e.g., smoking cessation, weight control) to reduce the risk of developing symptoms, or to moderate the severity of existing symptoms.[45]​

Offer supportive care to ensure optimum symptom management.

Monitor platelets regularly in all patients (including asymptomatic patients and those in a steady state after starting treatment).

Monitor all pregnant patients for new thrombosis, acquired von Willebrand disease, and/or disease-related major bleeding, particularly those who are high risk.

Consider – cytoreductive therapy: peginterferon

Back
ONGOING
|
pregnant: very low-, low-, or intermediate-risk
Consider – 

cytoreductive therapy: peginterferon

Treatment recommended for SOME patients in selected patient group

Cytoreductive therapy with peginterferon alfa-2a may be considered for very low-risk, low-risk, or intermediate-risk patients who are pregnant in certain situations (e.g., history of recurrent fetal loss; preeclampsia; uncontrolled leukocytosis/thrombocytosis; prominent splenomegaly).[10][37]​​​

Other cytoreductive agents (e.g., hydroxyurea, busulfan, anagrelide) cross the placenta and are potentially harmful to the fetus. Hydroxyurea, busulfan, and anagrelide should be avoided during pregnancy, particularly in the first trimester.

Primary options

peginterferon alfa 2a: consult specialist for guidance on dose

pregnant: high-risk

1st line – consider cytoreductive therapy: peginterferon

Back
ONGOING
|
pregnant: high-risk
1st line – 

consider cytoreductive therapy: peginterferon

Treating women with essential thrombocythemia during pregnancy is challenging due to the increased risk for first trimester spontaneous abortion, and thrombotic and obstetric complications.[10] Patients who become pregnant should be under the joint care of a hematologist and an obstetrician experienced in high-risk care.​

Cytoreductive therapy with peginterferon alfa-2a can be considered for high-risk patients who are pregnant.[10]

Other cytoreductive agents (e.g., hydroxyurea, busulfan, anagrelide) cross the placenta and are potentially harmful to the fetus. Hydroxyurea, busulfan, and anagrelide should be avoided during pregnancy, particularly in the first trimester.

Patients who are receiving hydroxyurea before pregnancy should be switched to peginterferon alfa-2a. Hydroxyurea is excreted in breastmilk and should be avoided in women who are breast-feeding.

Primary options

peginterferon alfa 2a: consult specialist for guidance on dose

Plus – lifestyle modification + supportive care + regular monitoring

Back
ONGOING
|
pregnant: high-risk
Plus – 

lifestyle modification + supportive care + regular monitoring

Treatment recommended for ALL patients in selected patient group

Cardiovascular risk factors (e.g., hypertension, hyperlipidemia, diabetes, smoking) should be identified and managed in all patients with essential thrombocythemia.​[37]​

Give advice on lifestyle modification (e.g., smoking cessation, weight control) to reduce the risk of developing symptoms, or to moderate the severity of existing symptoms.[45]​

Offer supportive care to ensure optimum symptom management.

Monitor platelets regularly in all patients (including asymptomatic patients and those in a steady state after starting treatment).

Monitor all pregnant patients for new thrombosis, acquired von Willebrand disease, and/or disease-related major bleeding, particularly those who are high risk.

Consider – antiplatelet therapy (for those with a history of arterial thrombosis)

Back
ONGOING
|
pregnant: high-risk
Consider – 

antiplatelet therapy (for those with a history of arterial thrombosis)

Treatment recommended for SOME patients in selected patient group

Pregnant high-risk patients with a history of arterial thrombosis should receive low-dose (once-daily) aspirin in combination with peginterferon alfa-2a.[10]​ 

Aspirin has been reported to be effective in reducing pregnancy complications, especially in patients with Janus kinase 2 (JAK2)-mutated essential thrombocythemia.[60]​ One systematic review reported a higher live birth rate among women with myeloproliferative neoplasms who were treated with aspirin alone or in combination with interferon.[61]

Aspirin should be used with caution and monitored closely in patients with acquired von Willebrand disease because of increased risk of bleeding.

Clopidogrel can be considered for pregnant patients if aspirin is contraindicated (e.g., due to allergy or peptic ulcer disease).

Primary options

aspirin: 81-100 mg orally once daily

Secondary options

clopidogrel: 75 mg orally once daily

Consider – anticoagulation (for those with a history of venous thrombosis)

Back
ONGOING
|
pregnant: high-risk
Consider – 

anticoagulation (for those with a history of venous thrombosis)

Treatment recommended for SOME patients in selected patient group

Pregnant high-risk patients with a history of venous thrombosis should receive systemic anticoagulation in combination with peginterferon alfa-2a.[10]​

Low molecular weight heparin (LMWH; e.g., enoxaparin) is the preferred anticoagulant for pregnant women.[10][37]​​​

LMWH does not cross the placenta and, in pregnant women, is associated with a lower risk of osteoporosis and heparin-induced thrombocytopenia (HIT) than unfractionated heparin (UFH).[62]

Primary options

enoxaparin: consult specialist for guidance on dose

Secondary options

heparin: consult specialist for guidance on dose

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Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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