Essential thrombocythaemia

Essential thrombocythaemia is a type of blood cell cancer that originates in the bone marrow. See section Leukaemia, bone marrow and blood cells.

Essential thrombocythemia (ET) is a malignant disease classified within the group of chronic myeloproliferative neoplasms, along with primary myelofibrosis and polycythemia vera, among others. The term chronic myeloproliferative syndromes was described in 1951 when it was observed that these diseases shared certain characteristics, such as the overproduction of blood cells, an increased frequency of thrombosis and hemorrhage, and the possibility of progression from one to another.

In the case of essential thrombocythemia, there is an uncontrolled increase in platelet production. The main function of platelets is to plug lesions that occur in blood vessels (arteries and veins). To do this, platelets aggregate to form a “platelet plug.” This process is called primary hemostasis and is the first phase of blood clotting. When the number of platelets is excessive, the body’s response to injury of a blood vessel may be greater than normal, leading to complete occlusion of the vessel, which is called thrombosis.

In our country, essential thrombocythemia is the most common chronic myeloproliferative syndrome. Its incidence is around 20 cases per million inhabitants per year. Most patients are between 50 and 60 years old, but up to 15-20% are young (age at diagnosis before 40).

We recommend reading the educational materials available in the Patient Area of ​​the website of the Spanish Group for Philadelphia-Negative Chronic Myeloproliferative Diseases (GEMFIN).

The causes of essential thrombocythemia and other chronic myeloproliferative disorders were unknown until recently. These are acquired, not hereditary, disorders; that is, they are not passed from parents to children. Since 2005, mutations in the JAK2, CALR, and MPL genes have been identified as the cause of these diseases. These mutations occur spontaneously, by chance, during the duplication of genetic material that takes place in the division of blood-producing stem cells. These stem cells multiply constantly throughout life to produce red blood cells, white blood cells, and platelets. In this cell division process, each stem cell gives rise to two daughter cells. For this to happen, the DNA, or genetic material that encodes all the information necessary for cellular life, must be copied accurately. It would be like making a handwritten copy of a 46-volume encyclopedia (chromosomes) in which each volume contains hundreds or thousands of chapters (genes). Each gene is composed of hundreds or thousands of nucleotides (equivalent to the letters in an encyclopedia entry).

Essential thrombocythemia is caused by mutations in one of the aforementioned genes (JAK2, CALR, and MPL). The most frequently mutated gene, in up to 60% of cases, is JAK2, located on chromosome 9. The most common mutation is called V617F and would result from changing a single letter in the encyclopedia entry, specifically in the chapter on the JAK2 gene in volume 9 (chromosome 9). In 20% of cases, the affected gene is CALR, located on chromosome 19. The most frequent mutations are type 1 and type 2, in which a small fragment of DNA is changed, resulting in a new genetic sequence (it’s as if a sentence in the encyclopedia were replaced with a completely new and different one). Another gene that can be mutated in up to 5-10% of patients is MPL, located on chromosome 1. Here, the genetic change is similar to that of JAK2 (a single-letter change). Around 10-15% of patients do not show any of these mutations. This group is called “triple negative.” As a consequence of mutations in these genes, stem cells evade the physiological mechanisms that regulate blood cell production, leading to an overproduction of platelets.

Currently, essential thrombocythemia and the other myeloproliferative syndromes are considered hematological neoplasms because, as a result of the aforementioned mutations, a group of identical cells arises that possess a greater proliferative capacity than normal, non-mutated cells. However, it is important to note that the proliferative advantage of the mutated cells in thrombocythemia is low compared to other hematological diseases such as leukemia, myeloma, or lymphoma.

In a significant percentage of patients, this disease is asymptomatic and is therefore diagnosed incidentally during routine blood tests.

Other patients, however, experience symptoms related to the disease, the most characteristic of which are:

• Burning pain in the lower extremities
• Gout attacks (intense pain in the big toe as a result of persistently elevated uric acid levels)
• Headaches, tingling in the hands and feet, and visual disturbances
• Bleeding: This can occur in any location and is more frequent in patients with high platelet counts and/or those taking antiplatelet drugs such as aspirin or anticoagulants.

The most frequent complication of essential thrombocythemia is thrombosis, which is the occlusion of a blood vessel by a clot. Thrombosis can affect both arteries and veins. The symptoms caused by thrombosis depend on the blood vessel that is obstructed. In the absence of specific treatment, thrombosis can have serious consequences, making early detection crucial for initiating treatment that allows for revascularization of the occluded vessel. The following are the common symptoms of the most frequent thromboses:

• Stroke (occlusion of arteries in the brain): sudden onset of inability to speak or move a part of the body, loss of vision.
• Acute myocardial infarction (occlusion of the coronary arteries that supply blood to the heart muscle): oppressive pain in the center of the chest, which may be accompanied by dizziness.
• Deep vein thrombosis (occlusion of a vein in the legs): swelling and pain in one of the legs (it may be below the knee or from the groin).
• Pulmonary thromboembolism (occlusion of the pulmonary arteries): sudden onset of shortness of breath or difficulty breathing.

In addition, patients with essential thrombocythemia may have thrombosis in anatomical territories that rarely affect the general population, such as the veins that carry blood to the liver or the veins that collect blood from the brain (cerebral venous sinuses).

First, blood tests allow us to establish a suspected diagnosis. In cases where the patient has platelet counts above 450 x 10⁹/L for more than three months, further testing is indicated. In addition to the elevated platelet count, some patients may also have an elevated white blood cell count.
These further tests consist of genetic testing using PCR (polymerase chain reaction). Initially, since it is the most common mutation, the JAK2 mutation is tested for. If this is negative, the presence of the other two mutations (CALR and MPL) is investigated. In patients who do not have any of these three mutations, the triple-negative patients, a more comprehensive molecular study called next-generation sequencing (NGS) can be requested. This allows us to detect the presence of other less frequent mutations or variants of the aforementioned genes.

Along with the genetic testing, a bone marrow biopsy is requested in most patients to complete the diagnosis. A bone marrow biopsy is a test that distinguishes essential thrombocythemia from other myeloproliferative disorders, including myelofibrosis, and also from other conditions in which thrombocytosis is reactive. It involves removing a small fragment of bone from the hip (about the size of a noodle). Local anesthesia and/or sedation are administered. In some cases, a bone marrow aspiration is also performed (a simpler test than a biopsy, which involves obtaining the fluid inside the bone through a puncture in the sternum or iliac crest).

The goals of essential thrombocythemia treatment are:

• To prevent thrombosis and bleeding.
• To control the symptoms of the disease.

To prevent arterial thrombosis, it is very important to achieve adequate control of cardiovascular risk factors. Although this control is usually the responsibility of the primary care physician, the hematologist typically provides some basic recommendations to reduce cardiovascular risk, including:

• Smoking cessation. Treatments to help people quit smoking are currently available in primary care.
• A healthy lifestyle that includes a Mediterranean-style diet and regular physical exercise adapted to the patient’s characteristics.
• In cases of elevated glucose levels, the patient is referred to primary care for diagnosis and evaluation of treatment, which may include diet with or without medication. The goal is to maintain glycated hemoglobin (HbA1c) below 7%.
• High blood pressure (hypertension). Blood pressure measurement is recommended, and if it is elevated (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg), a visit to the primary care physician is advised for monitoring. The goal is to maintain systolic blood pressure < 130 mmHg.
• Cholesterol measurement (Total, HDL, and LDL). Depending on the patient’s characteristics (age, history of thrombosis, systolic blood pressure, renal function, and cholesterol levels), the need for pharmacological treatment to reduce cholesterol levels is assessed. Not all patients with high cholesterol levels require medication.

In addition to these general measures, based on age, the presence of microvascular symptoms, cardiovascular risk factors, platelet count, and genotype, patients are stratified into different thrombosis risk groups, according to which the most appropriate treatment is determined.

When the hematologist considers the patient’s risk of thrombosis to be very low or low, cytoreductive therapy is generally not indicated. Within these low-risk groups, patients with the JAK2 mutation or cardiovascular risk factors are usually prescribed antiplatelet therapy with low-dose acetylsalicylic acid (aspirin) at 100 mg/day. Although most low- and very-low-risk patients will be monitored, there are special situations in which cytoreduction (treatment that reduces blood cell counts) may be indicated, such as platelet counts >1,500,000 x 10⁹/L, bleeding, or microvascular symptoms. Cytoreduction may also be indicated temporarily, for example, before scheduled surgery to reduce the associated risk of thrombosis.

In intermediate- and high-risk patients, it is considered best to initiate cytoreductive therapy to control the disease. The treatment of choice in most patients is hydroxyurea, although pegylated interferon is also frequently used in younger patients. The choice between these two modalities depends on multiple factors, so the treatment decision is usually made jointly by the hematologist and the patient. In patients in whom hydroxyurea does not adequately control the disease or whom the patient does not tolerate it, treatment with anagrelide may be indicated. As in low- and very-low-risk patients, antiplatelet therapy with acetylsalicylic acid (aspirin) at a low dose of 100 mg/day is also usually prescribed. Some patients are treated with oral anticoagulants, especially if they have experienced venous thrombosis or have an arrhythmia called atrial fibrillation. Combined antiplatelet and anticoagulant therapy is restricted to selected cases with a very high risk of thrombosis.

Currently, there is a great deal of research focused on improving the treatment of essential thrombocythemia, and as a result, a considerable number of new medications are in clinical trials. Your hematologist may offer you the opportunity to participate in a clinical trial.

Although there is no cure for the disease, currently available therapeutic options allow for adequate hematological control in most patients, resulting in a reduced risk of thrombosis and hemorrhage, as well as a life expectancy similar to that of the general population. Follow-up consists of blood tests and medical visits at varying intervals of approximately 4-6 months, depending on the type of treatment the patient is receiving. After several years (generally 10-20 years), a proportion of patients, around 10-20%, may progress to myelofibrosis. Leukemic transformation is rare, affecting less than 5% of patients.

• GEMFIN: Recommendations Manual for patients with Philadelphia-negative chronic proliferative neoplasms. Cooperative group of the Spanish Society of Hematology and Hemotherapy (SEHH).

• AEAL: Information on myeloproliferative syndromes.

• MPN Spain (Association of Patients Affected by Chronic Myeloproliferative Neoplasms)

• AELCLES (Spanish Association Against Leukemia and Blood Diseases)

• JOSEP CARRERAS FOUNDATION AGAINST LEUKEMIA

TESTIMONIAL MATERIALS

• Ebook “Here and now: Álvaro’s story”.
• Ebook “Here and now: Clàudia’s story”

You can order the booklets in paper format for free delivery in Spain by e-mail: imparables@fcarreras.es

BONE MARROW TRANSPLANT

• Bone Marrow Transplant Guide. Josep Carreras Foundation (content in Spanish)
• What is HLA and how does it work? Josep Carreras Foundation (content in Spanish)
• Graft-versus-Host Disease. Josep Carreras Foundation (content in Spanish)
• History of Bone Marrow Transplantation. Josep Carreras Foundation (content in Spanish)
• How is the search for an anonymous donor conducted? Josep Carreras Foundation (content in Spanish)

FOOD

• How to maintain a healthy diet during treatment? Josep Carreras Foundation (content in Spanish)
• Nutrition guide. Leukemia & Lymphoma Society

OTHER

• Ideas on what to take with me to the isolation chamber. Josep Carreras Leukaemia Foundation (content in Spanish)
• Travel tips for people with cancer. Josep Carreras Leukaemia Foundation (content in Spanish)
• Physiotherapy manual for haematological and transplant patients. Josep Carreras Leukaemia Foundation (content in Spanish)
• Prevention and treatment of oral mucositis. Josep Carreras Leukaemia Foundation (content in Spanish)
• Oral hygiene in oncohaematological patients. Josep Carreras Leukaemia Foundation (content in Spanish)
• Fertility manual: Suffering from blood cancer and becoming a parent. Josep Carreras Leukaemia Foundation (content in Spanish)
• Skin care in the oncohaematological patient. Josep Carreras Leukaemia Foundation (content in Spanish)
• Aesthetic Oncology Manual. Josep Carreras Leukaemia Foundation (content in Spanish)
• Leukaemia and sexuality. Josep Carreras Leukaemia Foundation (content in Spanish)
• 7 ways to wear a scarf. Josep Carreras Leukaemia Foundation (content in Spanish)

In Spain there is a large network of associations for haematological cancer patients that, in many cases, can inform you, advise you and even carry out certain procedures. These are the contacts of some of them by Autonomous Communities:

All these organisations are external to the Josep Carreras Foundation.

STATE

• MPN España (Asociación de Afectados Por Neoplasias Mieloproliferativas Crónicas)
• CEMMP (Comunidad Española de Pacientes de Mieloma Múltiple) 
• AEAL (ASOCIACIÓN ESPAÑOLA DE AFECTADOS POR LINFOMA, MIELOMA y LEUCEMIA)
• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present is the different provinces and in many municipalities. Contact with the nearest branch or call 900 100 036 (24h).
• AELCLES (Agrupación Española contra la Leucemia y Enfermedades de la Sangre)
• Josep Carreras Leukaemia Foundation
• FUNDACIÓN SANDRA IBARRA
• GEPAC (GRUPO ESPAÑOL DE PACIENTES CON CÁNCER)

ANDALUCÍA

• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present is the different provinces and in many municipalities. Contact the nearest branch.
• ALUSVI (ASOCIACIÓN LUCHA Y SONRÍE POR LA VIDA). Sevilla
• APOLEU (ASOCIACIÓN DE APOYO A PACIENTES Y FAMILIARES DE LEUCEMIA). Cádiz

ARAGÓN

• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present is the different provinces and in many municipalities. Contact the nearest branch.
• ASPHER (ASOCIACIÓN DE PACIENTES DE ENFERMEDADES HEMATOLÓGICAS RARAS DE ARAGÓN)
• DONA MÉDULA ARAGÓN

ASTURIAS

• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present is the different provinces and in many municipalities. Contact the nearest branch.
• ASTHEHA (ASOCIACIÓN DE TRASPLANTADOS HEMATOPOYÉTICOS Y ENFERMOS HEMATOLÓGICOS DE ASTURIAS)

CANTABRIA

• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present is the different provinces and in many municipalities. Contact the nearest branch.

CASTILLA LA MANCHA

• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present is the different provinces and in many municipalities. Contact the nearest branch.

CASTILLA LEÓN

• ABACES (ASOCIACIÓN BERCIANA DE AYUDA CONTRA LAS ENFERMEDADES DE LA SANGRE)
• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present is the different provinces and in many municipalities. Contact the nearest branch.
• ALCLES (ASOCIACIÓN LEONESA CON LAS ENFERMEDADES DE LA SANGRE). León.
• ASCOL (ASOCIACIÓN CONTRA LA LEUCEMIA Y ENFERMEDADES DE LA SANGRE). Salamanca.

CATALUÑA

• ASSOCIACIÓ FÈNIX. Solsona
• FECEC (FEDERACIÓ CATALANA D’ENTITATS CONTRA EL CÁNCER
• FUNDACIÓ KÁLIDA. Barcelona
• FUNDACIÓ ROSES CONTRA EL CÀNCER. Roses
• LLIGA CONTRA EL CÀNCER COMARQUES DE TARRAGONA I TERRES DE L’EBRE. Tarragona
• MielomaCAT 
• ONCOLLIGA BARCELONA. Barcelona
• ONCOLLIGA GIRONA. Girona
• ONCOLLIGA COMARQUES DE LLEIDA. Lleida
• ONCOVALLÈS. Vallès Oriental
• OSONA CONTRA EL CÀNCER. Osona
• SUPORT I COMPANYIA. Barcelona
• VILASSAR DE DALT CONTRA EL CÀNCER. Vilassar de Dalt

VALENCIAN COMMUNITY

• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present is the different provinces and in many municipalities. Contact the nearest branch.
• ASLEUVAL (ASOCIACIÓN DE PACIENTES DE LEUCEMIA, LINFOMA, MIELOMA Y OTRAS ENFERMEDADES DE LA SANGRE DE VALENCIA)

EXTREMADURA

• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present is the different provinces and in many municipalities. Contact the nearest branch.
• AFAL (AYUDA A FAMILIAS AFECTADAS DE LEUCEMIAS, LINFOMAS; MIELOMAS Y APLASIAS)
• AOEX (ASOCIACIÓN ONCOLÓGICA EXTREMEÑA)

GALICIA

• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present is the different provinces and in many municipalities. Contact the nearest branch.
• ASOTRAME (ASOCIACIÓN GALLEGA DE AFECTADOS POR TRASPLANTES MEDULARES)

BALEARIC ISLANDS

• ADAA (ASSOCIACIÓ D’AJUDA A L’ACOMPANYAMENT DEL MALALT DE LES ILLES BALEARS)
• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present is the different provinces and in many municipalities. Contact the nearest branch.

CANARY ISLANDS

• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present is the different provinces and in many municipalities. Contact the nearest branch.
• AFOL (ASOCIACIÓN DE FAMILIAS ONCOHEMATOLÓGICAS DE LANZAROTE)
• FUNDACIÓN ALEJANDRO DA SILVA

LA RIOJA

• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present is the different provinces and in many municipalities. Contact the nearest branch.

MADRID

• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present is the different provinces and in many municipalities. Contact the nearest branch.
• AEAL (ASOCIACIÓN ESPAÑOLA DE LEUCEMIA Y LINFOMA)
• CRIS CONTRA EL CÁNCER
• FUNDACIÓN LEUCEMIA Y LINFOMA

MURCIA

• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present is the different provinces and in many municipalities. Contact the nearest branch.

NAVARRA

• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present is the different provinces and in many municipalities. Contact the nearest branch.

BASQUE COUNTRY

• AECC (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER). Present is the different provinces and in many municipalities. Contact the nearest branch.
• PAUSOZ-PAUSO. Bilbao

AUTONOMOUS CITIES OF CEUTA AND MELILLA

• AECC CEUTA (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER)
• AECC MELILLA (ASOCIACIÓN ESPAÑOLA CONTRA EL CÁNCER)

We also invite you to follow us through our main social media (Facebook, Twitter and Instagram) where we often share testimonies of overcoming this disease.

If you live in Spain, you can also contact us by sending an e-mail to imparables@fcarreras.es so that we can help you get in touch with other people who have overcome this disease.