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Essential thrombocythemia

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Other Names:
Primary thrombocythemia; Hemorrhagic thrombocythemia; Essential thrombocytosis; Primary thrombocythemia; Hemorrhagic thrombocythemia; Essential thrombocytosis; Idiopathic thrombocythemia See More
Categories:
This disease is grouped under:
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 MPL, THPO, 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, hydroxyurea, anagrelide, 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]
Last updated: 11/24/2017
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.
Last updated: 11/24/2017

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.

Showing of 22 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal platelet morphology
Abnormal shape of platelets
0011875
Amaurosis fugax 0100576
Arterial thrombosis
Blood clot in artery
0004420
Chest pain 0100749
Increased megakaryocyte count 0005513
Myocardial infarction
Heart attack
0001658
Paresthesia
Pins and needles feeling
Tingling
[ more ] 		0003401
Prolonged bleeding time 0003010
Transient ischemic attack
Mini stroke
0002326
Venous thrombosis
Blood clot in vein
0004936
30%-79% of people have these symptoms
Splenomegaly
Increased spleen size
0001744
5%-29% of people have these symptoms
Acute leukemia 0002488
Myelodysplasia 0002863
Myelofibrosis 0011974
Percent of people who have these symptoms is not available through HPO
Abnormality of the skeletal system
Skeletal abnormalities
Skeletal anomalies
[ more ] 		0000924
Acrocyanosis
Persistent blue color of hands, feet, or parts of face
0001063
Autosomal dominant inheritance 0000006
Hypertension 0000822
Impaired platelet aggregation 0003540
Myeloproliferative disorder 0005547
Somatic mutation 0001428
Thrombocytosis
Increased number of platelets in blood
0001894
Showing of 22 |
Last updated: 7/1/2020
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 MPL, THPO, or TET2 gene. The proteins produced from the JAK2, MPL, 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]

Last updated: 11/24/2017
Most cases of essential thrombocythemia are not inherited. Instead, the condition arises from gene mutations that occur after conception (somatic mutations).[5]

Less commonly, essential thrombocythemia is inherited in an autosomal dominant pattern. This means that just one copy of the altered gene in each cell is sufficient to cause the condition. When essential thrombocythemia is inherited, it is called familial essential thrombocythemia.[5] In familial cases, an affected person has a 50% (1 in 2) chance of passing on the condition to each of his or her children.
Last updated: 11/24/2017
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]

Last updated: 11/24/2017

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 hydroxyurea, interferon-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]

Last updated: 11/24/2017

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.

Because the symptoms vary from person to person, the prognosis is also different from person to person. In general, most people can live for long periods of time without complications and have a normal life expectancy. Few people can have more serious problems such as stroke, severe heart or respiratory problems, or bleeding episodes in several parts of the body. Also, in very rare cases, the disease can transform into either primary myelofibrosis or acute myeloid leukemia.[1][4]
Last updated: 11/24/2017

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include the other myeloproliferative neoplasms (polycythemia vera, primary myelofibrosis, chronic myeloid leukemia; see these terms), myeloid malignancies (myelodysplastic syndrome), causes of secondary thrombocytosis (inflammation, cancer, iron deficiency, asplenia) and primary familial thrombocytosis (see this term).
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Essential thrombocythemia. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

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

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Financial Resources

  • Good Days provides help to patients with life-altering conditions. Assistance includes help with the cost of medications and travel.
  • Patient Access Network Foundation (PAN Foundation) has Assistance Programs for those with health insurance who reside in the United States. The disease fund status can change over time, so you may need to check back if funds are not currently available. 

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

  • Genetics Home Reference (GHR) contains information on Essential thrombocythemia. This website is maintained by the National Library of Medicine.
  • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
  • 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.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. Primary thrombocythemia. MedlinePlus Medical Encyclopedia. 2017; http://www.nlm.nih.gov/medlineplus/ency/article/000543.htm.
  2. Essential Thrombocythemia. National Cancer Institute. June 26, 2015; http://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; http://emedicine.medscape.com/article/206697-overview.
  5. Essential thrombocythemia. Genetics Home Reference (GHR). September, 2014; http://ghr.nlm.nih.gov/condition/essential-thrombocythemia.
  6. Essential thrombocythemia (ET). MPN Research Foundation. http://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: