hematology and oncology
Essential Thrombocythemia
Treatment of Essential Thrombocythemia
Sometimesaspirin Platelet-lowering medications (eg, pegylated interferon,anagrelide) Rarely plateletpheresis Rarely cytotoxic agents such ashydroxyurea Rarely stem cell transplantation Aspirin81 mg orally once a day is usually sufficient for mild vasomotor symptoms (eg, headache, mild digital ischemia, erythromelalgia) in low-risk patients (without cardiovascular disease) who do not have theJAK2mutation, but a higher dose may be used if necessary. Severe migraine may require platelet count reduction for control. The utility ofaspirinduring pregnancy is unproven and may provoke bleeding in patients with essential thrombocythemia and theCALRmutation. Women with essential thrombocythemia are thought to have a higher incidence of fetal loss in the first trimester. Patients without symptoms who use tobacco or have cardiovascular disease or cardiovascular risk factors are also treated withaspirin. The use ofaspirinfor cardiovascular prophylaxis in the absence of cardiovascular disease or risk factors in patients > 65 years of age is associated with an unacceptable incidence of adverse effects, particularly gastrointestinal hemorrhage. There is no proof that patients > 65 years without symptoms benefit fromaspirintherapy. is effective for controlling hemorrhage due to acquired Von Willebrand Disease during minor procedures such as dental work. Major procedures may require optimization of platelet counts. Platelet function can be assessed by measuring ristocetin cofactor activity. JAK2 inhibitors such asruxolitinibmay be effective for the treatment of essential thrombocythemia. Allogeneic Hematopoietic Stem Cell Transplantation is rarely used in essential thrombocythemia but can be effective if there is transformation to acute leukemia. Because prognosis is usually good and there is no correlation between degree of thrombocytosis and thrombosis, potentially toxic drugs that lower the platelet count should not be used just to normalize the platelet count in patients without symptoms. Generally agreed-upon indications for platelet-lowering therapy include Cardiovascular risk factors Transient ischemic attacks Tobacco use Significant bleeding Need for a surgical procedure in patients with extreme thrombocytosis and low ristocetin cofactor activity Sometimes severe migraine However, there are no data that prove cytotoxic therapy to reduce the platelet count lowers thrombotic risk or improves survival. Drugs used to lower platelet countincludeanagrelide,interferon alfa-2b, andhydroxyurea. Hydroxyurea, once considered the drug of choice for essential thrombocythemia therapy, has no benefit and is myelotoxic when used long-term. Hydroxyureashould be prescribed only by specialists familiar with its use and monitoring and never for long-term use. Patients are monitored with a weekly CBC. If the WBC count falls to<4000/mcL (<4×109/L),hydroxyureais withheld and reinstituted at 50% of the dose when the value normalizes. When a steady state is achieved, the interval between CBCs is lengthened to 2 weeks and then to 4 weeks. The aim is relief of symptoms and never for platelet count normalization. Too-rapid withdrawal ofhydroxyureacan result in rapid rebound to very high platelet levels and platelet cycling. Becauseanagrelideandhydroxyureacross the placenta, they are not used during pregnancy; pegylated interferon alfa-2a can be used in pregnant women when necessary. Anagrelideshould be used with caution in older patients because of its effects on the cardiovascular system (eg, palpitations, arrhythmias) and the kidneys (eg, fluid retention, renal failure). Interferon is the safest therapy for migraine when dedicated migraine drugs are not effective. in patients with partially treated essential thrombocythemia ( Treatment reference ). Platelet removal (plateletpheresis)has been used in rare patients with serious hemorrhage or recurrent thrombosis or before emergency surgery to immediately reduce the platelet count. However, plateletpheresis is rarely necessary. Its effects are transient with prompt rebound in the platelet count.Hydroxyureaoranagrelidedo not provide an immediate effect but should be started at the same time as plateletpheresis. 1.Harrison CN, Nangalia J, Boucher R, et al.RuxolitinibVersus Best Available Therapy for Polycythemia Vera Intolerant or Resistant toHydroxycarbamidein a Randomized Trial.J Clin Oncol2023;41(19):3534-3544. doi:10.1200/JCO.22.01935 