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The increased possibility of bleeding when the platelet count is over 1 million is due to von Willibrand factor (vWF) sequestration by the increased mass of platelets, leaving insufficient vWF for [[platelet]] adhesion.
The increased possibility of bleeding when the platelet count is over 1 million is due to von Willibrand factor (vWF) sequestration by the increased mass of platelets, leaving insufficient vWF for [[platelet]] adhesion.


A mutation in the [[JAK2]] [[kinase]] (V617F) has been found <ref name=Kralovics>{{cite journal | author=Kralovics R, Passamonti F, Buser AS, Teo SS, et al. |title=A gain-of-function mutation of JAK2 in myeloproliferative disorders| journal=N Engl J Med |year=2005 |volume=352|issue=17 |pages=1779–90 | doi=10.1056/NEJMoa051113 |pmid=15858187}}</ref><ref name=Baxter>{{cite journal |author=Baxter EJ, Scott LM, Campbell PJ, ''et al.'' |title=Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders |journal=Lancet |volume=365 |issue=9464 |pages=1054–61 |year=2005 |pmid=15781101 |doi=10.1016/S0140-6736(05)71142-9 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(05)71142-9}}</ref><ref name=Levine>{{cite journal |author=Levine RL, Wadleigh M, Cools J, ''et al.'' |title=Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis |journal=Cancer Cell |volume=7 |issue=4 |pages=387–97 |year=2005 |pmid=15837627 |doi=10.1016/j.ccr.2005.03.023 |url=http://linkinghub.elsevier.com/retrieve/pii/S1535-6108(05)00094-2}}</ref> 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.
A mutation in the [[JAK2]] [[kinase]] (V617F) has been found <ref name=Kralovics>{{cite journal | author=Kralovics R, Passamonti F, Buser AS, Teo SS, et al. |title=A gain-of-function mutation of JAK2 in myeloproliferative disorders| journal=N Engl J Med |year=2005 |volume=352|issue=17 |pages=1779–90 | doi=10.1056/NEJMoa051113 |pmid=15858187}}</ref><ref name=Baxter>{{cite journal |author=Baxter EJ, Scott LM, Campbell PJ, ''et al.'' |title=Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders |journal=Lancet |volume=365 |issue=9464 |pages=1054–61 |year=2005 |pmid=15781101 |doi=10.1016/S0140-6736(05)71142-9 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(05)71142-9}}</ref><ref name=Levine>{{cite journal |author=Levine RL, Wadleigh M, Cools J, ''et al.'' |title=Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis |journal=Cancer Cell |volume=7 |issue=4 |pages=387–97 |year=2005 |pmid=15837627 |doi=10.1016/j.ccr.2005.03.023 <ref>|url=http://linkinghub.elsevier.com/retrieve/pii/S1535-6108(05)00094-2}}</ref> in Et in 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. If This mutation may be helpful in making a diagnosis or as a target for future therapy.


==Clinical features==
==Clinical features==

Revision as of 21:28, 11 May 2014


Essential thrombocythemia
SpecialtyHematology Edit this on Wikidata

Essential thrombocythaemia (ET), (Essential thrombocytosis, Essential thrombocythemia, Primary thrombocytosis) is a rare chronic blood disorder characterized by the overproduction of platelets by megakaryocytes in the bone marrow.It may be progressive, and rarely may evolve into acute myeloid leukemia or myelofibrosis. It is one of four myeloproliferative disorders.

Epidemiology

The incidence of ET is 2 to 3 per 100,000 individuals annually.[1][2] ET is more likely to affect middle aged and elderly individuals, with an average age at diagnosis of 50–60 years. It can also affect children and young adults.[3]

Etiology

The etiology of ET is uncertain. ET shares with the developing red cells in polycythaemia vera the fact that developing megakaryocytes are more sensitive to growth factors. Platelets derived from the abnormal megakaryocytes are activated, which, along with the elevated platelet count, contributes to the likelihood thrombosis.

The increased possibility of bleeding when the platelet count is over 1 million is due to von Willibrand factor (vWF) sequestration by the increased mass of platelets, leaving insufficient vWF for platelet adhesion.

A mutation in the JAK2 kinase (V617F) has been found [4][5]Cite error: A <ref> tag is missing the closing </ref> (see the help page). in Et in 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. If This mutation may be helpful in making a diagnosis or as a target for future therapy.

Clinical features

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

The following revised diagnostic criteria for essential thrombocythaemia were proposed in 2005.[6] 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)[7]
  • 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

Indications

Not all patients will require treatment at presentation. In those who are at increased risk of thrombosis or bleeding: older age or prior history of bleeding or thrombosis, or sufficiently high platelet count, reduction of the platelet count should be considered.

Agents

Hydroxyurea (hydroxycarbamide), interferon-α andr anagrelide can lower the platelet count.  Low-dose aspirin is used to reduce the risk of thrombosis unless the platelet count is very high, where  theire is a risk of bleeding from the disease

The PT1 study[8] 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 and returns the remainder to the patient.

Prognosis

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.

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

  1. ^ Mesa R, Silverstein M, Jacobsen S, Wollan P, Tefferi A (1999). "Population-based incidence and survival figures in essential thrombocyhaemia 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  6. ^ 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.
  7. ^ http://bloodjournal.hematologylibrary.org/content/114/5/937.long
  8. ^ 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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)

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