In ET,
megakaryocytes are more sensitive to
growth factors.[7] Platelets derived from the abnormal megakaryocytes are activated, which, along with the elevated platelet count, contributes to the likelihood of forming blood clots.[8] The increased possibility of bleeding when the platelet count is over 1 million is due to
von Willebrand factor (vWF) sequestration by the increased mass of platelets, leaving insufficient vWF for
platelet adhesion.[8] A mutation in the
JAK2kinase (V617F) is present in 40–50% of cases and is diagnostic if present.[3][8]JAK2 is a member of the
Janus kinase family.[3][8]
In 2013, two groups detected
calreticulin mutations in a majority of
JAK2-negative/
MPL-negative patients with essential thrombocythemia and
primary myelofibrosis, which makes CALR mutations the second most common in
myeloproliferative neoplasms. All mutations (insertions or deletions) affected the last exon, generating a reading
frame shift of the resulting protein, that creates a novel terminal peptide and causes a loss of endoplasmic reticulum
KDEL retention signal.[9][10]
Diagnosis
The following revised diagnostic criteria for essential thrombocythemia were proposed in 2005.[11] The diagnosis requires the presence of both A criteria together with B3 to B6, or of criterion A1 together with B1 to B6.[12] The criteria are as follows:[12]
A1.
Platelet count > 400 × 103/µL for at least 2 months.
But the
Philadelphia chromosome may be present in up to 10% of cases. Patients with the Philadelphia chromosome have a potential for the development of acute leukemia, especially
acute lymphocytic leukemia.
no cytogenetic abnormalities suggestive of
myelodysplasia
Treatment
Indications
Not all those affected will require treatment at presentation.[13][14][15] Patients are usually designated as having a low or high risk of bleeding or developing blood clots based on their age, medical history, blood counts and their lifestyles. Low risk individuals are usually treated with
aspirin, whereas those at high risk are treated with
hydroxycarbamide,
interferon-α or
anagrelide).[3][13][14][15] Currently unapproved but in late-stage clinical trials (NCT04254978) are agents that lower platelets such as
bomedemstat.
Agents
Hydroxycarbamide,
interferon-α and
anagrelide can lower the platelet count. Low-dose aspirin is used to reduce the risk of blood clot formation unless the platelet count is very high, where there is a risk of bleeding from the disease, and hence this measure would be counter-productive as aspirin-use increases the risk of bleeding.[3][13][14][15]
The PT1 study compared hydroxyurea plus aspirin to anagrelide plus aspirin as initial therapy for ET. Hydroxyurea treated patients had a lower incidence of arterial thrombosis, lower incidence of severe bleeding and lower incidence of transformation to myelofibrosis, but the risk of venous thrombosis was higher with hydroxycarbamide than with anagrelide. It is unknown whether the results are applicable to all ET patients.[3][13][14][15] In people with symptomatic ET and extremely high platelet counts (exceeding 1 million),
plateletpheresis can be used to remove platelets from the blood to reduce the risk of thrombosis.[16]
Prognosis
Essential thrombocythemia is sometimes described as a slowly progressive disorder with long asymptomatic periods punctuated by thrombotic or hemorrhagic events.[13] However, well-documented medical regimens can reduce and control the number of platelets, which reduces the risk of these thrombotic or hemorrhagic events. The lifespan of a well-controlled ET person is well within the expected range for a person of similar age but without ET.[13] ET is the myeloproliferative neoplasm least likely to progress to acute myeloid leukemia.[17]
Epidemiology
The incidence of ET is 0.6-2.5/100,000 per year, the
median age at onset is 65–70 years and it is more frequent in females than in males.[2] The incidence in children is 0.09/100,000 per year.[2]
Pregnancy
Hydroxycarbamide and
anagrelide are contraindicated during
pregnancy and
nursing.[18] Essential thrombocythemia can be linked with a three-fold increase in risk of
miscarriage.[2] Throughout pregnancy, close monitoring of the mother and
fetus is recommended.[18] Low-dose
low molecular weight heparin (e.g.
enoxaparin) may be used.[18] For life-threatening complications, the platelet count can be reduced rapidly using
plateletpheresis, a procedure that removes platelets from the blood and returns the remainder to the patient.[18]
In popular culture
Jill Kaplan, the female protagonist of
The Pajama Diaries comic strip was diagnosed with essential thrombocythemia.[19]
^Tefferi, A (March 2011). "Annual Clinical Updates in Hematological Malignancies: a continuing medical education series: polycythemia vera and essential thrombocythemia: 2011 update on diagnosis, risk-stratification, and management". American Journal of Hematology. 86 (3): 292–301.
doi:
10.1002/ajh.21946.
PMID21351120.
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^Branehog I, Ridell B, Swolin B, Weinfeld A (1975). "Megakaryocyte quantifications in relation to thrombokinetics in primary thrombocythaemia and allied diseases". Scand. J. Haematol. 15 (5): 321–32.
doi:
10.1111/j.1600-0609.1975.tb01087.x.
PMID1060175.
^
abcdVannucchi, AM (June 2010). "Insights into the pathogenesis and management of thrombosis in polycythemia vera and essential thrombocythemia". Internal and Emergency Medicine. 5 (3): 177–84.
doi:
10.1007/s11739-009-0319-3.
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^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 (Dec 2013).
"Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2". The New England Journal of Medicine. 369 (25): 2391–405.
doi:
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^Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, Them NC, Berg T, Gisslinger B, Pietra D, Chen D, Vladimer GI, Bagienski K, Milanesi C, Casetti IC, Sant'Antonio E, Ferretti V, Elena C, Schischlik F, Cleary C, Six M, Schalling M, Schönegger A, Bock C, Malcovati L, Pascutto C, Superti-Furga G, Cazzola M, Kralovics R (Dec 2013).
"Somatic mutations of calreticulin in myeloproliferative neoplasms". The New England Journal of Medicine. 369 (25): 2379–90.
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