Guideline sources The following summarized guidelines for the evaluation and management of essential thrombocythemia (ET) are prepared by our editorial team based on guidelines from the European Leukemia Net (ELN 2018), the European Society of Medical Oncology (ESMO 2015), the British Committee for Standards In Haematology (BCSH 2012), and the British Society for Haematology (BSH 2010). 1 2 3 4 Calculator Calculator Revised IPSET score for essenti WHO criteria for essential throm Guidelines 1. Screening and diagnosis https://web.pathway.md/diseases/recmSleoxzC8TqF9W 1/6 6/29/23, 4:19 AM Essential thrombocythemia Pathway Indications for testing: evaluate all patients with unexplained splanchnic vein thrombosis for the presence of myeloproliferative neoplasms even if the blood count is normal. B Diagnostic criteria: As per ELN 2018 guidelines, use the 2016 revised WHO criteria for diagnosis of ET. E As per ESMO 2015 guidelines, ensure accurate differentiation among the three unique myeloproliferative neoplasm subtypes as well as the exclusion of reactive conditions (in mutation-negative patients only) and disorders, such as myelodysplasia and chronic myeloid leukemia, for appropriate prognosis and treatment decision-making. Do not use the generic diagnostic label 'myeloproliferative neoplasm' alone. A 2. Classification and risk stratification Risk of thrombosis: As per ELN 2018 guidelines: Use the IPSET-thrombosis system (including age, previous thrombosis, cardiovascular risk factors, and JAK2V617F mutation) for prognostic purposes in all patients at diagnosis of ET. E Consider assessing general risk factors for thrombosis, including smoking history, diabetes mellitus, hypertension, and hyperlipidemia. E As per ESMO 2015 guidelines, categorize patients with newly diagnosed myeloproliferative neoplasm at baseline according to the risks associated with the disease. B As per BSH 2010 guidelines, stratify patients according to their risk of thrombotic complications as follows: Situation Guidance Age > 60 years, or High risk History of ET-related thrombotic or hemorrhagic event, or Platelet count of > 1, 500 10 /L Age 40-60 years with no high-risk features Intermediate risk Age < 40 years with no high-risk features. B Low risk Show 3 more 3. Diagnostic investigations Genetic testing: As per ELN 2018 guidelines, obtain mutational analysis for JAK2V617F, CALR, and MPL on peripheral blood or bone marrow samples in patients with suspected ET. E https://web.pathway.md/diseases/recmSleoxzC8TqF9W 2/6 6/29/23, 4:19 AM Essential thrombocythemia Pathway As per ESMO 2015 guidelines, obtain testing for 3 driver mutations in all patients with suspected myeloproliferative neoplasms. B 4. Diagnostic procedures Bone marrow biopsy: perform bone marrow biopsy in all patients with suspected Philadelphia chromosome-negative myeloproliferative neoplasms, except for patients with polycythemia vera with Hgb > 18.5 g/dL in males and > 16.5 g/dL in females. E 5. Medical management Treatment target: As per ESMO 2015 guidelines, set an optimal platelet target of < 400 10 /L (although unvalidated) in patients with ET. B As per BSH 2010 guidelines, return the platelet count into the normal range as the target of treatment. B Cytoreductive therapy: As per ELN 2018 guidelines, administer hydroxyurea, recombinant interferon-alpha, or anagrelide to produce a hematological response in high-risk patients with ET. Administer hydroxyurea or recombinant interferon-alpha as first-line therapy agents. E Show 2 more Landmark trials: ANAHYDRET In patients with essential thrombocythemia who have high-risk profile, anagrelide was noninferior to hydroxyurea with respect to a ET-related major and minor thrombohemorrhagic events at 6 months. Gisslinger H et al. Blood. 2013 Mar 7. As per ESMO 2015 guidelines, administer hydroxyurea as first-line cytoreductive therapy in patients with high-risk ET. Consider initiating interferon, or sometimes anagrelide, as first-line therapy in specific groups of patients. B Show 2 more Landmark trials: Hydroxyurea versus anagrelide in high-risk ET In patients with essential thrombocythemia who were at high-risk for vascular events and already receiving low-dose aspirin, hydroxyurea was superior to anagrelide with respect to arterial or venous thrombosis, serious hemorrhage, or death from vascular causes. Harrison CN et al. N Engl J Med. 2005 Jul 7. Antiplatelet therapy: https://web.pathway.md/diseases/recmSleoxzC8TqF9W 3/6 6/29/23, 4:19 AM Essential thrombocythemia Pathway As per ELN 2018 guidelines, initiate low-dose aspirin in all patients with IPSET-thrombosis high-risk disease as well as in patients with low- or intermediate-risk ET when reaching age 60 years, or when uncontrolled cardiovascular risk factors or JAK2V617F mutation are present. E As per ESMO 2015 guidelines, initiate low-dose aspirin in all patients with ET without clear contraindications to aspirin. B As per BSH 2010 guidelines, initiate aspirin in all patients with ET unless contraindicated. B 6. Perioperative care Preoperative management: consider controlling blood counts preoperatively to standard targets in high-risk patients undergoing surgery, when bleeding is a risk or thromboprophylaxis would normally be prescribed. C 7. Specific circumstances Pediatric patients: Exclude reactive thrombocytosis rigorously and diagnose ET only in the presence of definitive diagnostic features. B Insufficient evidence to guide the management of ET in pediatric patients, however, offer a conservative approach where possible. I Pregnant patients: manage pregnant patients with ET by a multidisciplinary team. E Show 3 more Breastfeeding patients: recognize that breastfeeding is contraindicated with cytoreductive therapy. Decide about breastfeeding while taking interferon on an individual basis after discussion regarding possible risks and benefits. B Patients on hormonal therapy: As per ESMO 2015 guidelines: Obtain an individualized risk-benefit assessment to decide on hormonal therapy. B Advise using progesterone-only preparations for oral contraception and avoid combined oral contraceptives. B As per BSH 2010 guidelines, discourage the use of combined oral contraceptives in female patients with ET. E Show 2 more Patients undergoing surgery: obtain individual risk assessment (including disease-, patient-, and procedure-specific risks) for VTE in patients undergoing surgery, and offer appropriate graded elastic compression stockings and pharmacotherapy. E Show 4 more Patients with leukemic transformation: As per ESMO 2015 guidelines, consider administering acute leukemia-like regimens in patients with leukemic transformation deemed potential candidates for allo-SCT. Consider offering azacitidine. C https://web.pathway.md/diseases/recmSleoxzC8TqF9W 4/6 6/29/23, 4:19 AM Essential thrombocythemia Pathway As per BSH 2010 guidelines: Diagnose leukemic transformation when 20% blasts are consistently present either in blood or bone marrow. E Recognize that most patients with leukemic transformation have poor overall survival. Consider offering stem cell transplantation in patients with leukemic transformation. B Patients with post-ET myelofibrosis: As per BCSH 2012 guidelines, consider using the International Prognostic Scoring System, DIPSS, and DIPSS-plus prognostic scores in patients with post-ET myelofibrosis. C As per BSH 2010 guidelines, obtain regular monitoring (3-yearly) for early signs of progression because of the risks of myelofibrotic transformation in patients receiving anagrelide treatment. B Show 3 more Clinical findings Patient demographics Symptoms Elderly Abdominal discomfort Bone pain Past medical history Chest pain Easy bruising Acquired vWD Fainting Acute coronary syndrome Fatigue DVT Generalized pruritus PE Gingival bleeding Splanchnic vein thrombosis Headache Stroke Lightheadedness TIA Night sweats Integument exam Nosebleed Paresthesia Ecchymosis Tinnitus Erythromelalgia Visual disturbances Skin erythema Weight loss Hematological findings Abdominal exam blood platelet count Splenomegaly Lab findings ESR serum CRP serum LDH Genetic testing Calr gene mutation https://web.pathway.md/diseases/recmSleoxzC8TqF9W 5/6 6/29/23, 4:19 AM Essential thrombocythemia Pathway Jak2 gene mutation Studies 2013 ANAHYDRET In patients with essential thrombocythemia who have high-risk profile, anagrelide was noninferior to hydroxyurea with respect to a ET-related major and minor thrombohemorrhagic events at 6 months. Gisslinger H et al. Blood. 2013 Mar 7. 2005 Hydroxyurea versus anagrelide in high-risk ET In patients with essential thrombocythemia who were at high-risk for vascular events and already receiving low-dose aspirin, hydroxyurea was superior to anagrelide with respect to arterial or venous thrombosis, serious hemorrhage, or death from vascular causes. Harrison CN et al. N Engl J Med. 2005 Jul 7. References 1. Claire N Harrison, David Bareford, Nauman Butt et al. Guideline for investigation and management of adults and children presenting with a thrombocytosis. Br J Haematol. 2010 May;149 3 352 75. Open 2. Tiziano Barbui, Ayalew Tefferi, Alessandro M Vannucchi et al. Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet. Leukemia. 2018 May;32 5 1057 1069. Open 3. A M Vannucchi, T Barbui, F Cervantes et al. Philadelphia chromosome-negative chronic myeloproliferative neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015 Sep;26 Suppl 5:v85 99. Open 4. John T Reilly, Mary Frances McMullin, Philip A Beer et al. Guideline for the diagnosis and management of myelofibrosis. Br J Haematol. 2012 Aug;158 4 453 71. Open 5. Mahnur Haider, Naseema Gangat, Terra Lasho et al. Validation of the revised International Prognostic Score of Thrombosis for Essential Thrombocythemia IPSET-thrombosis) in 585 Mayo Clinic patients. Am J Hematol. 2016 Jun;91 4 390 4. Open https://web.pathway.md/diseases/recmSleoxzC8TqF9W 6/6