Essential thrombocythemia

Most people with essential thrombocythemia are without symptoms at the time of diagnosis, which is usually made after noting an elevated platelet level on a routine complete blood count (CBC).[4] The most common symptoms are bleeding (due to dysfunctional platelets), blood clots (e.g., deep vein thrombosis or pulmonary embolism), fatigue, headache, nausea, vomiting, abdominal pain, visual disturbances, dizziness, fainting, and numbness in the extremities; the most common signs are increased white blood cell count, reduced red blood cell count, and an enlarged spleen.[4][5][6]

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 JAK2 kinase (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]

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.
• 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 polycythemia vera
  • hematocrit < midpoint of normal range or normal red cell mass in presence of normal iron stores
• B4. No evidence of chronic myeloid leukemia
  • 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 (using 0–4 scale)
• B6. No evidence of a myelodysplastic syndrome
  • no significant dysplasia
  • no cytogenetic abnormalities suggestive of myelodysplasia

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]

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]

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]

Jill Kaplan, the female protagonist of The Pajama Diaries comic strip was diagnosed with essential thrombocythemia.[19]