Essential thrombocythaemia

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Essential thrombocythaemia
Classification and external resources
ICD-10 D75.2, D47.3
ICD-9 238.71
ICD-O: M9962/3
OMIM 187950
DiseasesDB 4522
MedlinePlus 000543
eMedicine med/2266
MeSH D013920

Essential thrombocythaemia (ET, also known as Essential thrombocytosis or Essential thrombocythemia) or Primary thrombocytosis (PT) is a rare chronic blood disorder characterized by the overproduction of platelets by megakaryocytes in the bone marrow in the absence of an alternative cause. In some cases this disorder may be progressive, and rarely may evolve into acute myeloid leukemia or myelofibrosis. It is one of four myeloproliferative disorders.

Epidemiology[edit]

Essential thrombocythaemia is diagnosed at a rate of about 2 to 3 per 100,000 individuals annually.[1][2] The disease usually affects middle aged to elderly individuals, with an average age at diagnosis of 50–60 years, although it can affect children and young adults as well.[3]

Pathophysiology[edit]

The pathologic basis for this disease is unknown. However, essential thrombocythaemia resembles polycythaemia vera in that cells of the megakaryocytic series are more sensitive to growth factors. Platelets derived from the abnormal megakaryocytes do not function properly, which contributes to the clinical features of bleeding and thrombosis. A mutation in the JAK2 kinase (V617F) has been found [4][5][6] to be associated with essential thrombocythaemia in around 40–50% of cases. About 3–4% of such cases go on to develop acute leukemia. JAK2 is a member of the Janus kinase family. This mutation may be helpful in making a diagnosis or as a target for future therapy.

Clinical features[edit]

The major symptoms are bleeding and thrombosis. Other symptoms include epistaxis (nosebleeds) and bleeding from gums and gastrointestinal tract. One characteristic symptom is throbbing and burning of the hands and feet due to the occlusion of small arterioles by platelets (erythromelalgia). An enlarged spleen (splenomegaly) may be found on examination.

Diagnostic criteria[edit]

The diagnosis of essential thrombocythaemia requires the presence of a persistent thrombocytosis of greater than 600 × 103/µL in the absence of an alternative cause.

The following revised diagnostic criteria for essential thrombocythaemia were proposed in 2005.[7] The diagnosis requires the presence of both A criteria together with B3 to B6, or of criterion A1 together with B1 to B6.

  • A1. Platelet count > 600 × 103/µL for at least 2 months. (Note: the 2008 WHO panel lowered the platelet count criterion to 450 × 103/µL)[8]
  • A2. Acquired V617F JAK2 mutation present
  • B1. No cause for a reactive thrombocytosis
    • normal inflammatory indices
  • B2. No evidence of iron deficiency
    • stainable iron in the bone marrow or normal red cell mean corpuscular volume
  • B3. No evidence of polycythaemia vera
    • hematocrit < midpoint of normal range or normal red cell mass in presence of normal iron stores
  • B4. No evidence of chronic myeloid leukemia
  • B5. No evidence of myelofibrosis
    • no collagen fibrosis and ≤ grade 2 reticulin fibrosis (using 0–4 scale)
  • B6. No evidence of a myelodysplastic syndrome
    • no significant dysplasia
    • no cytogenetic abnormalities suggestive of myelodysplasia

Treatment[edit]

Not all patients will require treatment at presentation. In those who are at increased risk of thrombosis or bleeding (older age, prior history of bleeding or thrombosis, or very high platelet count), reduction of the platelet count to the normal range can be achieved using hydroxyurea (also known as hydroxycarbamide), interferon-α or anagrelide. Low-dose aspirin is widely used to reduce the risk of thrombosis, but there may be an increased risk of bleeding if aspirin is initiated while the platelet count is very high.

The PT1 study[9] compared hydroxyurea in combination with aspirin to anagrelide in combination with aspirin as initial therapy for essential thrombocytosis. Hydroxyurea was superior, with lower risk of arterial thrombosis, lower risk of severe bleeding and lower risk of transformation to myelofibrosis (although the rate of venous thrombosis was higher with hydroxycarbamide than with anagrelide).

In rare cases where patients have life-threatening complications, the platelet count can be reduced rapidly using platelet apheresis (a procedure that removes platelets from the blood directly).

Prognosis[edit]

Essential thrombocytosis is sometimes described as a slowly progressive disorder with long asymptomatic periods punctuated by thrombotic or hemorrhagic events.

However, well-documented medical regimens can reduce and control the number of platelets, which reduces the risk of these thrombotic or haemorrhagic events. The lifespan of a well controlled ET person is well within the expected range for a person of similar age but without ET.

Special care related to pregnancy[edit]

Hydroxyurea and anagrelide are contraindicated during pregnancy and nursing. There is current debate as to the safety of interferon during pregnancy and nursing. Essential thrombocytosis can be linked with increased risk of spontaeous abortion or miscarriage in the first trimester of pregnancy. Throughout pregnancy, close monitoring of the mother for thrombosis and placenta is recommended to ensure blood clots are caught. Post partum, often daily injections of low dose low molecular weight heparin (e.g. enoxaparin) are prescribed for several weeks as this is a period where the mother is at higher risk of developing a blood clot.

References[edit]

  1. ^ Mesa R, Silverstein M, Jacobsen S, Wollan P, Tefferi A (1999). "Population-based incidence and survival figures in essential thrombocythemia and agnogenic myeloid metaplasia: an Olmsted County Study, 1976-1995". Am J Hematol 61 (1): 10–5. doi:10.1002/(SICI)1096-8652(199905)61:1<10::AID-AJH3>3.0.CO;2-I. PMID 10331505. 
  2. ^ Kutti J, Ridell B (2001). "Epidemiology of the myeloproliferative disorders: essential thrombocythaemia, polycythaemia vera and idiopathic myelofibrosis". Pathol Biol (Paris) 49 (2): 164–6. PMID 11317963. 
  3. ^ Hoffman: Hematology: Basic Principles and Practice, 4th ed., 2005 Churchill Livingstone, Chapter 71.
  4. ^ Kralovics R, Passamonti F, Buser AS, Teo SS, et al. (2005). "A gain-of-function mutation of JAK2 in myeloproliferative disorders". N Engl J Med 352 (17): 1779–90. doi:10.1056/NEJMoa051113. PMID 15858187. 
  5. ^ Baxter EJ, Scott LM, Campbell PJ, et al. (2005). "Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders". Lancet 365 (9464): 1054–61. doi:10.1016/S0140-6736(05)71142-9. PMID 15781101. 
  6. ^ Levine RL, Wadleigh M, Cools J, et al. (2005). "Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis". Cancer Cell 7 (4): 387–97. doi:10.1016/j.ccr.2005.03.023. PMID 15837627. 
  7. ^ Campbell PJ, Green AR (2005). "Management of polycythemia vera and essential thrombocythemia". Hematology Am Soc Hematol Educ Program 2005: 201–8. doi:10.1182/asheducation-2005.1.201. PMID 16304381. 
  8. ^ http://bloodjournal.hematologylibrary.org/content/114/5/937.long
  9. ^ Harrison CN, Campbell PJ, Buck G, et al. (2005). "Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia". N. Engl. J. Med. 353 (1): 33–45. doi:10.1056/NEJMoa043800. PMID 16000354. 

External links[edit]