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Thrombocythemia 1(THCYT1)

MedGen UID:
479301
Concept ID:
C3277671
Disease or Syndrome
Synonyms: Idiopathic thrombocythemia; MPL-Related Essential Thrombocythemia; THCYT1; THPO-Related Essential Thrombocythemia; THROMBOCYTHEMIA, SOMATIC; THROMBOCYTOSIS 1
 
Genes (locations): CALR (19p13.13); SH2B3 (12q24.12); THPO (3q27.1)
 
Monarch Initiative: MONDO:0008554
OMIM®: 187950

Definition

Thrombocythemia, or thrombocytosis, is a myeloproliferative disorder characterized by excessive platelet production resulting in increased numbers of circulating platelets. Thrombocythemia can be associated with thrombotic or hemorrhagic episodes and occasional leukemic transformation (summary by Wiestner et al., 1998). Genetic Heterogeneity of Thrombocythemia THCYT2 (601977) is caused by germline or somatic mutation in the THPO receptor gene (MPL; 159530) on chromosome 1p34, and THCYT3 (614521) is caused by germline or somatic mutation in the JAK2 gene (147796) on chromosome 9p. Somatic mutations in the TET2 (612839), ASXL1 (612990), SH2B3 (605093), and SF3B1 (605590) genes have also been found in cases of essential thrombocythemia. Somatic mutation in the CALR gene (109091) occurs in approximately 70% of essential thrombocythemia patients who lack JAK2 and MPL mutations (Klampfl et al., 2013; Nangalia et al., 2013). [from OMIM]

Additional description

From MedlinePlus Genetics
Essential thrombocythemia is a condition characterized by an increased number of platelets (thrombocythemia). Platelets (thrombocytes) are blood cells 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.  https://medlineplus.gov/genetics/condition/essential-thrombocythemia

Clinical features

From HPO
Thrombocytosis
MedGen UID:
163397
Concept ID:
C0836924
Disease or Syndrome
Increased numbers of platelets in the peripheral blood.
Impaired collagen-induced platelet aggregation
MedGen UID:
870264
Concept ID:
C4024703
Finding
Abnormal response to collagen or collagen-mimetics as manifested by reduced or lacking aggregation of platelets upon addition collagen or collagen-mimetics.
Impaired epinephrine-induced platelet aggregation
MedGen UID:
870285
Concept ID:
C4024727
Finding
Abnormal response to epinephrine as manifested by reduced or lacking aggregation of platelets upon addition of epinephrine.
Impaired ADP-induced platelet aggregation
MedGen UID:
870824
Concept ID:
C4025282
Finding
Abnormal platelet response to ADP as manifested by reduced or lacking aggregation of platelets upon addition of ADP.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.

Professional guidelines

PubMed

Harrison CN
Semin Thromb Hemost 2006 Apr;32(3):283-8. doi: 10.1055/s-2006-939440. PMID: 16673283

Recent clinical studies

Etiology

Ryou H, Sirinukunwattana K, Aberdeen A, Grindstaff G, Stolz BJ, Byrne H, Harrington HA, Sousos N, Godfrey AL, Harrison CN, Psaila B, Mead AJ, Rees G, Turner GDH, Rittscher J, Royston D
Leukemia 2023 Feb;37(2):348-358. Epub 2022 Dec 5 doi: 10.1038/s41375-022-01773-0. PMID: 36470992Free PMC Article
Godfrey AL, Campbell PJ, MacLean C, Buck G, Cook J, Temple J, Wilkins BS, Wheatley K, Nangalia J, Grinfeld J, McMullin MF, Forsyth C, Kiladjian JJ, Green AR, Harrison CN; United Kingdom Medical Research Council Primary Thrombocythemia-1 Study; United Kingdom National Cancer Research Institute Myeloproliferative Neoplasms Subgroup; French Intergroup of Myeloproliferative Neoplasms; the Australasian Leukaemia and Lymphoma Group.
J Clin Oncol 2018 Dec 1;36(34):3361-3369. Epub 2018 Aug 28 doi: 10.1200/JCO.2018.78.8414. PMID: 30153096Free PMC Article
Harrison CN, Campbell PJ, Buck G, Wheatley K, East CL, Bareford D, Wilkins BS, van der Walt JD, Reilly JT, Grigg AP, Revell P, Woodcock BE, Green AR; United Kingdom Medical Research Council Primary Thrombocythemia 1 Study
N Engl J Med 2005 Jul 7;353(1):33-45. doi: 10.1056/NEJMoa043800. PMID: 16000354

Diagnosis

Ryou H, Sirinukunwattana K, Aberdeen A, Grindstaff G, Stolz BJ, Byrne H, Harrington HA, Sousos N, Godfrey AL, Harrison CN, Psaila B, Mead AJ, Rees G, Turner GDH, Rittscher J, Royston D
Leukemia 2023 Feb;37(2):348-358. Epub 2022 Dec 5 doi: 10.1038/s41375-022-01773-0. PMID: 36470992Free PMC Article
Godfrey AL, Campbell PJ, MacLean C, Buck G, Cook J, Temple J, Wilkins BS, Wheatley K, Nangalia J, Grinfeld J, McMullin MF, Forsyth C, Kiladjian JJ, Green AR, Harrison CN; United Kingdom Medical Research Council Primary Thrombocythemia-1 Study; United Kingdom National Cancer Research Institute Myeloproliferative Neoplasms Subgroup; French Intergroup of Myeloproliferative Neoplasms; the Australasian Leukaemia and Lymphoma Group.
J Clin Oncol 2018 Dec 1;36(34):3361-3369. Epub 2018 Aug 28 doi: 10.1200/JCO.2018.78.8414. PMID: 30153096Free PMC Article

Therapy

Ryou H, Sirinukunwattana K, Aberdeen A, Grindstaff G, Stolz BJ, Byrne H, Harrington HA, Sousos N, Godfrey AL, Harrison CN, Psaila B, Mead AJ, Rees G, Turner GDH, Rittscher J, Royston D
Leukemia 2023 Feb;37(2):348-358. Epub 2022 Dec 5 doi: 10.1038/s41375-022-01773-0. PMID: 36470992Free PMC Article
Godfrey AL, Campbell PJ, MacLean C, Buck G, Cook J, Temple J, Wilkins BS, Wheatley K, Nangalia J, Grinfeld J, McMullin MF, Forsyth C, Kiladjian JJ, Green AR, Harrison CN; United Kingdom Medical Research Council Primary Thrombocythemia-1 Study; United Kingdom National Cancer Research Institute Myeloproliferative Neoplasms Subgroup; French Intergroup of Myeloproliferative Neoplasms; the Australasian Leukaemia and Lymphoma Group.
J Clin Oncol 2018 Dec 1;36(34):3361-3369. Epub 2018 Aug 28 doi: 10.1200/JCO.2018.78.8414. PMID: 30153096Free PMC Article
Harrison CN, Campbell PJ, Buck G, Wheatley K, East CL, Bareford D, Wilkins BS, van der Walt JD, Reilly JT, Grigg AP, Revell P, Woodcock BE, Green AR; United Kingdom Medical Research Council Primary Thrombocythemia 1 Study
N Engl J Med 2005 Jul 7;353(1):33-45. doi: 10.1056/NEJMoa043800. PMID: 16000354

Prognosis

Ryou H, Sirinukunwattana K, Aberdeen A, Grindstaff G, Stolz BJ, Byrne H, Harrington HA, Sousos N, Godfrey AL, Harrison CN, Psaila B, Mead AJ, Rees G, Turner GDH, Rittscher J, Royston D
Leukemia 2023 Feb;37(2):348-358. Epub 2022 Dec 5 doi: 10.1038/s41375-022-01773-0. PMID: 36470992Free PMC Article
Godfrey AL, Campbell PJ, MacLean C, Buck G, Cook J, Temple J, Wilkins BS, Wheatley K, Nangalia J, Grinfeld J, McMullin MF, Forsyth C, Kiladjian JJ, Green AR, Harrison CN; United Kingdom Medical Research Council Primary Thrombocythemia-1 Study; United Kingdom National Cancer Research Institute Myeloproliferative Neoplasms Subgroup; French Intergroup of Myeloproliferative Neoplasms; the Australasian Leukaemia and Lymphoma Group.
J Clin Oncol 2018 Dec 1;36(34):3361-3369. Epub 2018 Aug 28 doi: 10.1200/JCO.2018.78.8414. PMID: 30153096Free PMC Article
Harrison CN, Campbell PJ, Buck G, Wheatley K, East CL, Bareford D, Wilkins BS, van der Walt JD, Reilly JT, Grigg AP, Revell P, Woodcock BE, Green AR; United Kingdom Medical Research Council Primary Thrombocythemia 1 Study
N Engl J Med 2005 Jul 7;353(1):33-45. doi: 10.1056/NEJMoa043800. PMID: 16000354

Clinical prediction guides

Ryou H, Sirinukunwattana K, Aberdeen A, Grindstaff G, Stolz BJ, Byrne H, Harrington HA, Sousos N, Godfrey AL, Harrison CN, Psaila B, Mead AJ, Rees G, Turner GDH, Rittscher J, Royston D
Leukemia 2023 Feb;37(2):348-358. Epub 2022 Dec 5 doi: 10.1038/s41375-022-01773-0. PMID: 36470992Free PMC Article

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