Rare Gastroenterology News

Disease Profile

Essential thrombocythemia

Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

1-5 / 10 000

US Estimated

Europe Estimated

Age of onset

All ages





Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.


Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.


dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.


recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.


Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.


Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.


Not applicable


Other names (AKA)

Primary thrombocythemia; Hemorrhagic thrombocythemia; Essential thrombocytosis;


Blood Diseases; Rare Cancers


Essential thrombocythemia belongs to a group of diseases called myeloproliferative neoplasms, which cause the bone marrow to make too many platelets, white blood cells and/or red blood cells. In essential thrombocythemia, the body produces too many platelets. The signs and symptoms vary from person to person, but most people with essential thrombocythemia do not have any symptoms when the platelet cell count first increases. Signs and symptoms that develop as the disease progresses include:[1][2]

  • increased production of megakaryocytes (a type of cell in the bone marrow that is responsible for making platelets);
  • enlargement of the spleen (splenomegaly); and
  • bleeding in several parts of the body and/or clotting episodes such as strokes, pain in the legs and difficulty breathing.

Other symptoms may include weakness, headaches, or a burning, tingling or prickling sensation in the skin. Some people have episodes of severe pain, redness, and swelling (especially in the hands and feet).[3]

Essential thrombocythemia may be caused by a person acquiring (not inheriting) a somatic mutation in any of several genes, such as the JAK2 gene (most frequently), CALR gene, and rarely, the MPLTHPO, or TET2 gene.[4][5] The reason why some people acquire mutations that cause the disease is unknown.[6] Treatment may include low-dose aspirin, hydroxyureaanagrelide, and/or interferon-alpha. Most people with the disease can live long lives. In very rare cases, essential thrombocythemia can transform into either primary myelofibrosis or acute myeloid leukemia.[4][6][7]


Essential thrombocythemia is more common (80% of cases) in older people. Most cases are diagnosed around 60 years of age. Around 25-33% of people with this disease may not have any symptoms. The symptoms are varied and may include: [1][4][8]

  • Blood clots that may form in several organs of the body, and may result in:
    • Symptoms such as headache, dizziness, chest pain, fainting, numbness or tingling sensations of the hands and feet
    • Redness, throbbing and burning pain in the hands and feet (erythromelalgia)
    • Blood clot occurring in the arteries that supply the brain and may cause ministrokes (transient ischemic attack (TIA), or strokes, leading to weakness or numbness of the face, arm or leg, trouble speaking, and vision problems
    • Thrombosis in the legs can cause leg pain, swelling, or both
    • Clots that can travel to the lungs (pulmonary embolism), blocking blood flow in the lungs and causing chest pain and difficulty breathing (dyspnea)
  • Bleeding episodes (when platelet count is very high (more than 1 million platelets per microliter of blood) that usually don't require transfusions, and may include:
    • nosebleeds
    • easy bruising
    • bleeding from the mouth or gums
    • bloody stool or anal bleeding due to bleeding in the intestines (40% of cases)
  • Enlarged spleen (splenomegaly)
  • Weakness
  • Swollen lymph nodes (rare)
  • Prolonged bleeding caused by surgical procedures or removal of a tooth
  • Ulcers of the fingers or toes
  • Microvascular occlusions (in arteries or small caliber veins) in fingers or toes leading to gangrene
  • Unpleasant moods (dysphoria)
  • Seeing spots or lights (Scotomas)
  • Complications in pregnancy that can result in abortion.

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
80%-99% of people have these symptoms
Abnormal platelet morphology
Abnormal shape of platelets
Amaurosis fugax
Arterial thrombosis
Blood clot in artery
Chest pain
Increased megakaryocyte count
Myocardial infarction
Heart attack
Pins and needles feeling

[ more ]

Prolonged bleeding time
Transient ischemic attack
Mini stroke
Venous thrombosis
Blood clot in vein
30%-79% of people have these symptoms
Increased spleen size
5%-29% of people have these symptoms
Acute leukemia
1%-4% of people have these symptoms
Impaired ADP-induced platelet aggregation
Impaired collagen-induced platelet aggregation
Impaired epinephrine-induced platelet aggregation
Increased number of platelets in blood
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance


Essential thrombocythemia may be caused by acquiring somatic mutations (not inherited mutations) in any of several genes, including the JAK2 gene (most frequently) and CALR gene. In rare cases, the disease is caused by mutations in the MPLTHPO, or TET2 gene. The proteins produced from the JAK2MPL, and THPO genes work together to regulate a signaling pathway called the JAK/STAT pathway, which transmits messages to the cell nucleus to produce blood cells. It is believed that mutations in these genes lead to an increase in the production of platelets in the bone marrow.[4][5]

The reason that mutations in the CALR and TET2 genes cause essential thrombocythemia is not known. The CALR gene provides instructions for creating a protein called calreticulin that has many functions, such as aiding the functioning of the immune system and wound healing. The TET2 gene produces a protein that is thought to be important for the production of blood cells.[3][4][9]

In some cases, no genetic mutation is identified in a person with essential thrombocthemia, and the cause is not known. It is thought that these cases may be due to mutations in genes that are not yet known to be associated with the disease.[4][5]


The diagnosis of essential thrombocytemia can be made when people who meet criteria 1-5 and more than three of criteria 6-11:[4] 

  1. Platelet count greater than 600,000/mm3 on two different occasions with a 1-month interval among them
  2. No identifiable cause of secondary thrombocytosis
  3. Having normal red blood cell mass
  4. Bone marrow fibrosis that is less than one third of the bone marrow
  5. Absence of the Philadelphia chromosome (Ph) by a blood exam that examines the chromosomes (karyotyping) or absence of the "bcr-abl fusion product"
  6. Splenomegaly detected by physical examination or seen in ultrasonography
  7. High number of cell in the bone marrow and increased size of the megakaryocyte
  8. Abnormal blood producing cells in the bone marrow
  9. Normal levels of CRP and IL-6
  10. Absence of iron deficiency anemia
  11. Clonal hematopoiesis in which stem cells that produce blood cells help to form blood cells that have a unique mutation because these cells are derived from a single founding cell and are genetic "clones" of the original cells.

Most of the time, the disease is found through blood tests, showing high number of platelets, done for other conditions before symptoms appear. Tests may include:[1]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.


    Before starting the treatment, it is recommended to determine the risks of having complications according to the age, medical history and the presence of specific mutations to decide which the best treatment should be. The available treatments are not curative and do not prevent further evolution of the disease to acute myeloid leukemia or myelofibrosis (which only happens in very rare cases). The treatment of essential thrombocythemia is based in reducing the platelet count to avoid complications. The most common medication include hydroxyureainterferon-alpha, Phosphorus 32, anagrelide. Aspirin in low doses can be used to control microvascular symptoms such as redness and pain in the fingers and toes, insufficient blood flow (ischemia), infections in the limbs (gangrene), strokes, syncopes, instability or visual disturbances.[1][4][10]

    The classification of the disease according to the risks is as following:[7]

    • High-risk disease: People who had thrombosis at any age and/or who are older than 60 years of age and have a JAK2 V617F mutation
    • Intermediate-risk disease: People who are older than 60 years of age, who do not have a JAK2 mutation and who never had thrombosis
    •  Low-risk disease: People who are 60 years of age or younger, and who have a JAK2 mutation and never had thrombosis
    •  Very-low-risk disease: People who are 60 years of age or younger without a JAK2 mutation and never had thrombosis.

    Recent studies have made the following recommendations:[7]

    • People who have a high risk of thrombosis or who had thrombosis should use a cytoreductor in combination with an anticoagulant
    • People with high or intermediate risk, should be treated with a cytoreductor in combination with aspirin at low doses 
    • People who are at low risk should be treated with low doses of aspirin or are only observed carefully without any type of treatment

    Hydroxyurea is the preferred cytoreductive drug for most people, because it is less toxic and has a lower risk of producing myelofibrosis. However, in pregnant women and in those women who wish to become pregnant, interferon is used because hydroxyurea or anagrelide may cause birth defects.[4][7]

    Management Guidelines

    • The NORD Physician Guide for Essential thrombocythemia was developed as a free service of the National Organization for Rare Disorders (NORD) and it's medical advisors. The guides provide a resource for clinicians about specific rare disorders to facilitate diagnosis and treatment of their patients with this condition.

      FDA-Approved Treatments

      The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.


      Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

      Organizations Supporting this Disease

        Social Networking Websites

          Learn more

          These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

          Where to Start

          • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
          • Genetics Home Reference (GHR) contains information on Essential thrombocythemia. This website is maintained by the National Library of Medicine.
          • The Merck Manuals Online Medical Library provides information on this condition for patients and caregivers.
          • The MPN Research Foundation provides online information on myeloproliferative disorders (MPD). Click on the link to view the resource.
          • The National Cancer Institute provides the most current information on cancer for patients, health professionals, and the general public.
          • The National Heart, Lung, and Blood Institute (NHLBI) has information on this topic. NHLBI is part of the National Institutes of Health and supports research, training, and education for the prevention and treatment of heart, lung, and blood diseases.
          • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

            In-Depth Information

            • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
            • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
            • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
            • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
            • PubMed is a searchable database of medical literature and lists journal articles that discuss Essential thrombocythemia. Click on the link to view a sample search on this topic.


              1. Primary thrombocythemia. MedlinePlus Medical Encyclopedia. 2017; https://www.nlm.nih.gov/medlineplus/ency/article/000543.htm.
              2. Essential Thrombocythemia. National Cancer Institute. June 26, 2015; https://www.cancer.gov/types/myeloproliferative/patient/chronic-treatment-pdq#link/stoc_h2_4.
              3. CALR gene. Genetics Home Reference. 2014; https://ghr.nlm.nih.gov/gene/CALR#conditions.
              4. Lal A. Essential Thrombocytosis. Medscape. 2016; https://emedicine.medscape.com/article/206697-overview.
              5. Essential thrombocythemia. Genetics Home Reference (GHR). September, 2014; https://ghr.nlm.nih.gov/condition/essential-thrombocythemia.
              6. Essential thrombocythemia (ET). MPN Research Foundation. https://www.mpnresearchfoundation.org/Essential-Thrombocythemia. Accessed 2/11/2019.
              7. Tefferi A. Prognosis and treatment of essential thrombocythemia. UpToDate. September 08, 2017; https://www.uptodate.com/contents/prognosis-and-treatment-of-essential-thrombocythemia.
              8. Essential thrombocythemia. Mayo Clinic. 2017; https://www.mayoclinic.org/es-es/diseases-conditions/essential-thrombocythemia/symptoms-causes/syc-20361064.
              9. TET2 gene. Genetics Home Reference. 2014; https://ghr.nlm.nih.gov/gene/TET2.
              10. Tefferi A. Myeloproliferative disorders: Essential thrombocythemia and primary myelofibrosis. In: Goldman L & Ausiello D. Cecil Medicine 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007; 177:

              Rare Gastroenterology News