In ET, 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 of forming blood clots. The increased possibility of bleeding when the platelet count is over 1 million is due to von Willebrand factor sequestration by the increased mass of platelets, leaving insufficient vWF for platelet adhesion. A mutation in the JAK2kinase is present in 40–50% of cases and is diagnostic if present. JAK2 is a member of the Janus kinase family. 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 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 reticulumKDEL retention signal.
Diagnosis
The following revised diagnostic criteria for essential thrombocythaemia were proposed in 2005. The diagnosis requires the presence of both A criteria together with B3 to B6, or of criterion A1 together with B1 to B6. The criteria are as follows:
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.
B5. No evidence of myelofibrosis
* no collagen fibrosis and ≤ grade 2 reticulin fibrosis
Not all those affected will require treatment at presentation. People are usually split up into low and high risk for bleeding/blood clotting groups, low risk individuals are usually treated with aspirin, whereas those at high risk are given hydroxycarbamide and/or other treatments that reduce platelet count.
Agents
, 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. 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. In people with symptomatic ET and extremely high platelet counts, plateletpheresis can be used to remove platelets from the blood to reduce the risk of thrombosis.
Prognosis
Essential thrombocythemia 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 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. ET is the myeloproliferative neoplasm least likely to progress to acute myeloid leukemia.
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. The incidence in children is 0.09/100,000 per year.
Pregnancy
and anagrelide are contraindicated during pregnancy and nursing. Essential thrombocythemia can be linked with a three-fold increase in risk of miscarriage. Throughout pregnancy, close monitoring of the mother and fetus is recommended. Low-dose low molecular weight heparin may be used. 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.
