Essential Thrombocythemia (ET)
WHAT IS ESSENTIAL THROMBOCYTHEMIA (ET)?
Essential Thrombocythemia (ET) is a chronic myeloproliferative neoplasm (MPN) characterized by an increased number of platelets in the blood. Most commonly diagnosed in women over the age of 50, ET is associated with a proliferation of platelet precursors in the bone marrow and complications frequently include blood clotting and/or bleeding. Less common consequences in the later stages of ET include a transformation to myelofibrosis (marrow scarring) or acute leukemia.
WHAT CAUSES ET?
No one knows what causes the onset of essential thrombocythemia (ET) or other myeloproliferative neoplasms (MPNs). Like many other MPNs, ET is not a genetically inherited disorder, but there may be a familial predisposition to the disease in some patients.
However, researchers have discovered mutations that alter the activity of proteins that control signaling pathways (important regulators of cell growth and development) in many patients with ET. Signaling pathways are important regulators of cell growth and development.
Risk factors associated with ET include:
Women are 1.5 times more likely than men to develop essential thrombocythemia.
People older than 60 are most likely to develop the condition, although 20% of ET sufferers are under the age of 40.
Approximately half of all ET patients have a mutation of the JAK2 gene in their blood-forming cells. This mutation leads to hyperactive JAK (Janus kinase) signaling, causing the body to make the wrong number of blood cells.
Nearly a quarter (23.5%) of those diagnosed with MF and ET have a mutation called Calreticulin, or CALR. Discovered in 2013 by two independent laboratories, the identification of the CALR genetic marker has potential implications for treatments and prognosis for those with ET.
HOW IS ET DIAGNOSED?
ET is often suspected after a routine blood test shows that a patient has a high platelet count. Other patients may consult their physician after experiencing one or more symptoms of ET.
Based on diagnostic tests and a review of patient history and symptoms, a physician can determine whether a patient has ET, and whether his/her case can be categorized as having low or high risk.
Common tests for diagnosing ET include:
Blood tests can exclude other causes of a high platelet count (“reactive”). This often includes tests for iron deficiency and indicators of inflammation as well as other mimicking blood diseases.
Bone Marrow Biopsy
A bone marrow biopsy may be done to look for classical signs of ET (e.g., an increase in platelet precursors) or to exclude an early phase of MF.
Gene Mutation Analysis of Blood Cells
Physicians may also test for gene mutations like JAK2 (occurring in approximately 50% of cases), CALR (occurring in 23.5% of cases) or MPL (occurring in up to 5% of cases).
WHAT ARE THE SYMPTOMS OF ET?
Many ET patients are asymptomatic. Consequently, the disease is often diagnosed as part of a routine check-up, after a blood test reveals a high platelet count. When symptoms are present, they may include fatigue, or may be related to small or large vessel disturbance or bleeding.
Common ET Symptoms related to small vessel disturbances may include:
• Vision disturbances or silent migraines
• Dizziness or lightheadedness
• Coldness or blueness of fingers or toes
• Burning, redness, and pain in the hands and feet
When bleeding is present as a symptom of essential thrombocythemia, it can manifest as:
• Easy bruising, nosebleeds or heavy periods
• Gastrointestinal bleeding or blood in the urine
Thrombotic complications can also occur, resulting in:
• Transient ischemic attack (TIA)
• Heart attack
• Deep vein thrombosis or pulmonary emblous (blood clot in the lung)
• Blood clotting in unusual locations, such as the abdominal veins
WHAT IS THE PROGNOSIS FOR ET?
When properly monitored and treated, essential thrombocythemia patients have an excellent chance of longevity.
ET is a chronic hematologic malignancy, so it is important for patients to regularly consult with a hematologist and to report any symptoms such as visual disturbances, unexplained pain, numbness, tingling or bruising. Patients who experience symptoms from ET will require treatment.
A small minority of people with ET may later develop acute leukemia (less than 10%) or postpolycythemic myelofibrosis (15%), both of which can be life threatening.
WHAT ARE THE AVAILABLE TREATMENTS FOR ET?
As with other MPNs, there is no single treatment option that is appropriate or effective for all ET sufferers. While some ET patients may be asymptomatic and require no treatment, others may require various treatments and therapies, based on the symptoms and the results of routine monitoring by a physician.
The decision to use platelet-lowering agents depends on a variety of risk factors, history of bleeding or thrombosis, vascular risk, and the severity of symptoms. The decision is usually made based on factors other than the platelet count itself, unless the platelet count is extremely elevated (>1.5 million) or clearly associated with symptoms. The choice of treatments is generally based on a variety of risk factors including age, history of thrombotic events, and drug tolerance.
When treatment is necessary, the available treatment options for ET patients include:
Low-dose aspirin is usually given to reduce the risk of blood clotting. Aspirin may also help relieve the burning sensation that some ET patients experience in their hands and feet (erythromelalgia, along with other vasomotor symptoms).
Hydroxyurea is often used to treat ET patients at high risk for clotting (over 60 years-old or patients with a prior blood clot). It is usually considered the first line agent for patients that require treatment.
Anagrelide is another option for lowering platelet counts. It is frequently used after a patient has demonstrated intolerance or experienced complications with Hydroxyurea.
Interferon (typically pegylated) is sometimes prescribed for ET patients. Women of childbearing age are often treated with interferon because it hasn’t been shown to cause birth defects.
Novel Therapies and Treatments
Potential new treatments for ET are currently being developed and tested as a result of the discovery of the link between the JAK2 mutation and the incidence of ET. Pegylated interferon, a version of interferon with fewer side effects and easier administration, is being considered as a treatment option for high-risk individuals.