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Genetics Home Reference: your guide to understanding genetic conditions
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Essential thrombocythemia

Reviewed September 2014

What is essential thrombocythemia?

Essential thrombocythemia is a condition characterized by an increased number of platelets (thrombocythemia). Platelets (thrombocytes) are blood cell fragments involved in blood clotting. While some people with this condition have no symptoms, others develop problems associated with the excess platelets.

Abnormal blood clotting (thrombosis) is common in people with essential thrombocythemia and causes many signs and symptoms of this condition. Clots that block blood flow to the brain can cause strokes or temporary stroke-like episodes known as transient ischemic attacks. Thrombosis in the legs can cause leg pain, swelling, or both. In addition, clots can travel to the lungs (pulmonary embolism), blocking blood flow in the lungs and causing chest pain and difficulty breathing (dyspnea).

Another problem in essential thrombocythemia is abnormal bleeding, which occurs more often in people with a very high number of platelets. Affected people may have nosebleeds, bleeding gums, or bleeding in the gastrointestinal tract. It is thought that bleeding occurs because a specific protein in the blood that helps with clotting is reduced, although why the protein is reduced is unclear.

Other signs and symptoms of essential thrombocythemia include an enlarged spleen (splenomegaly); weakness; headaches; or a sensation in the skin of burning, tingling, or prickling. Some people with essential thrombocythemia have episodes of severe pain, redness, and swelling (erythromelalgia), which commonly occur in the hands and feet.

How common is essential thrombocythemia?

Essential thrombocythemia affects an estimated 1 to 24 per 1 million people worldwide.

What genes are related to essential thrombocythemia?

The JAK2 and CALR genes are the most commonly mutated genes in essential thrombocythemia. The MPL, THPO, and TET2 genes can also be altered in this condition. The JAK2, MPL, and THPO genes provide instructions for making proteins that promote the growth and division (proliferation) of blood cells. The CALR gene provides instructions for making a protein with multiple functions, including ensuring the proper folding of newly formed proteins and maintaining the correct levels of stored calcium in cells. The TET2 gene provides instructions for making a protein whose function is unknown.

The proteins produced from the JAK2, MPL, and THPO genes are part of a signaling pathway called the JAK/STAT pathway, which transmits chemical signals from outside the cell to the cell's nucleus. These proteins work together to turn on (activate) the JAK/STAT pathway, which promotes the proliferation of blood cells, particularly platelets and their precursor cells, megakaryocytes.

Mutations in the JAK2, MPL, and THPO genes that are associated with essential thrombocythemia lead to overactivation of the JAK/STAT pathway. The abnormal activation of JAK/STAT signaling leads to overproduction of megakaryocytes, which results in an increased number of platelets. Excess platelets can cause thrombosis, which leads to many signs and symptoms of essential thrombocythemia.

Although mutations in the CALR and TET2 genes have been found in people with essential thrombocythemia, it is unclear how these gene mutations are involved in development of the condition.

Some people with essential thrombocythemia do not have a mutation in any of the known genes associated with this condition. Researchers are working to identify other genes that may be involved in the condition.

Related Gene(s)

Changes in these genes are associated with essential thrombocythemia.

  • CALR
  • JAK2
  • MPL
  • TET2
  • THPO

How do people inherit essential thrombocythemia?

Most cases of essential thrombocythemia are not inherited. Instead, the condition arises from gene mutations that occur in early blood-forming cells after conception. These alterations are called somatic mutations.

Less commonly, essential thrombocythemia is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. When it is inherited, the condition is called familial essential thrombocythemia.

Where can I find information about diagnosis or management of essential thrombocythemia?

These resources address the diagnosis or management of essential thrombocythemia and may include treatment providers.

  • Cleveland Clinic: Thrombocytosis (http://my.clevelandclinic.org/health/diseases_conditions/hic_Thrombocytosis)
  • Genetic Testing Registry: Essential thrombocythemia (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0040028)
  • Merck Manual for Health Care Professionals: Essential Thrombocythemia (http://www.merckmanuals.com/professional/hematology_and_oncology/myeloproliferative_disorders/essential_thrombocythemia.html)

You might also find information on the diagnosis or management of essential thrombocythemia in Educational resources (http://www.ghr.nlm.nih.gov/condition/essential-thrombocythemia/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/essential-thrombocythemia/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about essential thrombocythemia?

You may find the following resources about essential thrombocythemia helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for essential thrombocythemia?

  • essential thrombocytosis
  • primary thrombocythemia
  • primary thrombocytosis

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about essential thrombocythemia?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding essential thrombocythemia?

autosomal ; autosomal dominant ; blood clotting ; calcium ; cell ; clotting ; dyspnea ; embolism ; enlarged spleen ; familial ; gastrointestinal ; gene ; gums ; inherited ; mutation ; nucleus ; platelets ; precursor ; proliferation ; protein ; pulmonary ; pulmonary embolism ; splenomegaly ; thrombocytes ; thrombosis ; transient

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

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  • Merck Manual for Health Care Professionals: Essential Thrombocythemia (http://www.merckmanuals.com/professional/hematology_and_oncology/myeloproliferative_disorders/essential_thrombocythemia.html)
  • Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC, Avezov E, Li J, Kollmann K, Kent DG, Aziz A, Godfrey AL, Hinton J, Martincorena I, Van Loo P, Jones AV, Guglielmelli P, Tarpey P, Harding HP, Fitzpatrick JD, Goudie CT, Ortmann CA, Loughran SJ, Raine K, Jones DR, Butler AP, Teague JW, O'Meara S, McLaren S, Bianchi M, Silber Y, Dimitropoulou D, Bloxham D, Mudie L, Maddison M, Robinson B, Keohane C, Maclean C, Hill K, Orchard K, Tauro S, Du MQ, Greaves M, Bowen D, Huntly BJ, Harrison CN, Cross NC, Ron D, Vannucchi AM, Papaemmanuil E, Campbell PJ, Green AR. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med. 2013 Dec 19;369(25):2391-405. doi: 10.1056/NEJMoa1312542. Epub 2013 Dec 10. (http://www.ncbi.nlm.nih.gov/pubmed/24325359?dopt=Abstract)
  • Rumi E, Pietra D, Ferretti V, Klampfl T, Harutyunyan AS, Milosevic JD, Them NC, Berg T, Elena C, Casetti IC, Milanesi C, Sant'antonio E, Bellini M, Fugazza E, Renna MC, Boveri E, Astori C, Pascutto C, Kralovics R, Cazzola M; Associazione Italiana per la Ricerca sul Cancro Gruppo Italiano Malattie Mieloproliferative Investigators. JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes. Blood. 2014 Mar 6;123(10):1544-51. doi: 10.1182/blood-2013-11-539098. Epub 2013 Dec 23. (http://www.ncbi.nlm.nih.gov/pubmed/24366362?dopt=Abstract)
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  • Tefferi A, Pardanani A, Lim KH, Abdel-Wahab O, Lasho TL, Patel J, Gangat N, Finke CM, Schwager S, Mullally A, Li CY, Hanson CA, Mesa R, Bernard O, Delhommeau F, Vainchenker W, Gilliland DG, Levine RL. TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis. Leukemia. 2009 May;23(5):905-11. doi: 10.1038/leu.2009.47. Epub 2009 Mar 5. (http://www.ncbi.nlm.nih.gov/pubmed/19262601?dopt=Abstract)
  • Tefferi A. Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1. Leukemia. 2010 Jun;24(6):1128-38. doi: 10.1038/leu.2010.69. Epub 2010 Apr 29. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20428194?dopt=Abstract)
  • Wiestner A, Schlemper RJ, van der Maas AP, Skoda RC. An activating splice donor mutation in the thrombopoietin gene causes hereditary thrombocythaemia. Nat Genet. 1998 Jan;18(1):49-52. (http://www.ncbi.nlm.nih.gov/pubmed/9425899?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: September 2014
Published: December 16, 2014