Essential Thrombocythemia (ET)

What is ET?
Symptoms
Diagnosis
Progression
Prognosis/Life Expectancy
Available Treatments
Possible Causes
Prevalence

What is ET?

Essential Thrombocythemia (ET) is a chronic myeloproliferative neoplasm characterized by an increased number of platelets in the circulating blood. The disease is commonly diagnosed at the age of 60, predominately in women. ET is characterized by a proliferation of platelet precursors in the bone marrow, and its most common complications include tendencies toward blood clotting and/or bleeding; later but more rare consequences include a transformation to myelofibrosis (marrow scarring) or acute leukemia

Symptoms

Many patients are asymptomatic, diagnosed after blood counts as part of a routine check-up reveal a high platelet count. When symptoms are present, they may include fatigue, or may be related to small or large vessel disturbance or bleeding.

Small vessel disturbances (often considered vasomotor in nature) can lead to:

• Headache
• Vision disturbances or silent migraines 
• Dizziness or lightheadedness
• Coldness or blueness of fingers or toes 
• Burning, redness, and pain in the hands and feet

Thrombotic complications can be quite serious, leading to:
• Stroke
• Transient ischemic attack (TIA)
• Heart attack
• Deep vein thrombosis or Pulmonary Embolus (blood clot in the lung)

Bleeding can manifest as: 
• Easy bruising, nosebleeds or heavy periods 
• Gastrointestinal bleeding or blood in the urine

Diagnosis

ET is often diagnosed after a routine blood test shows that a patient has a high platelet count. Other patients may consult their physician as a result of one or more of the symptoms shown above. 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.

Tests which may be done to diagnose ET include the following:

• Blood tests to exclude other causes of a high platelet count (“reactive”). This often includes tests for iron deficiency and indicators of inflammation; other mimicking blood diseases can be ruled out as well

• Tests for gene mutations JAK2 (occurring in approximately 50% of cases) or MPL ( occurring in up to 5% of cases)

• Bone marrow biopsy to look for classical signs of ET, including an increase in platelet precursors

Progression

A small minority of people with ET may later develop acute leukemia or myelofibrosis, both of which can be life-threatening:
• Acute leukemia. Acute myelogenous leukemia (AML) is a type of blood and bone marrow cancer that progresses rapidly
• Myelofibrosis. This progressive bone marrow disorder results in bone marrow scarring, severe anemia, and enlargement of your liver and spleen

Prognosis/Life Expectancy

Essential thrombocythemia patients have an excellent chance of living out a normal life span if properly monitored and treated as necessary. ET is a chronic hematologic malignancy and it is prudent to be monitored regularly by a hematologist. It is important to report any symptoms such as visual disturbances, unexplained pain, numbness, tingling or bruising to your physician. For those who have had symptoms from their ET, treatment will be required.

Possible Causes

No one knows exactly what triggers the start of essential thrombocythemia (ET) or other myeloproliferative neoplasms (MPNs). Recently, researchers discovered mutations that alter the activity of proteins that control signaling pathways in many patients with MPN. Signaling pathways are important regulators of cell growth and development.

About half of all people with essential thrombocythemia have a mutation called "JAK2V617F" (found in the JAK2 gene) within their blood-forming cells. This mutation leads to hyperactive JAK (Janus kinase) signaling and leads to many  of the characteristic features of the disease. The end result is that the body makes the wrong number of blood cells. Recently, clusters of families with MPN have been described, suggesting a familial predisposition in some patients.
Some epidemiological risk factors associated with ET include the following:
• Gender -- Women are 1.5 times more likely than men to develop the condition
• Age -- People older than 60 are most likely to develop the condition, although 20% of those with this condition are under 40
• Environment – Exposure to chemicals or to electrical wiring may increase an individual's risk for the condition

Available Treatments

You should consult your doctor about available treatments that may be appropriate for you. Essential thrombocythemia (ET) is different in every person. If you don’t have a lot of symptoms, your doctor may decide that you don't need treatment yet. Instead, your doctor will observe and monitor your condition.

Current treatments for ET patients who require treatment include the following:

• Low-dose aspirin is usually given to reduce the risk of blood clotting. Aspirin may also help relieve the burning sensation that some people get in their hands and feet (erythromelalgia, along with other vasomotor symptoms)
• Hydroxyurea is often used in essential thrombocythemia in people at high risk for clotting (age over 60 and those with a prior blood clot), and is usually considered the first line agent in those that require treatment
• Anagrelide is another option to lower the platelet count, often chosen after a patient has intolerance or complications with Hydroxyurea
• Interferon is sometimes prescribed for ET patients. Younger women of childbearing age are often treated with interferon because it hasn't been shown to cause birth defects. A pegylated version may be associated with less side effects and easier administration

The decision to use platelet lowering agents depends on a variety of risk factors including platelet count, history of bleeding or thrombosis, vascular risk, and severity of symptoms. The choice of treatments is generally based on a variety of risk factors including age, history or thrombotic events, and drug tolerance.

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 incidence of ET. These drugs, referred to as JAK2 Inhibitors, are currently in early stages of testing for ET. Pegylated interferon is also being considered as a treatment in those with high risk disease.

Prevalence

A common question often has to do with the prevalence and incidence of MPN; these terms refer to the total number of patients currently living with disease and the number of newly diagnosed patients each year, respectively.

To investigate this further, the MPN Research Foundation co-sponsored with the Leukemia and Lymphoma Society a grant to assess the prevalence of MPNs. Dr. Xiaomei Ma of Yale University School of Medicine was the lead investigator on the study on prevalence of MPDs that was published in the American Journal of Hematology (1). The study looked exclusively at the prevalence of the MPNs PV and ET, excluding Myelofibrosis.

According to this study on the prevalence of MPNs, there are 22 cases of PV and 24 cases of ET per 100,000. The study says there is an estimated total of 65,243 patients with PV and 71,078 with ET in the United States in 2003, for a total of approximately 136,000 patients. This number may be increased as the discovery of the JAK2 mutation has facilitated the diagnostic work-up. Another study has evaluated national databases to determine the number of new cases per year (Rollison et al, Blood 2008)

The Yale study did not look at the prevalence of Myelofibrosis patients. However, a study by the Mayo Clinic reported an incidence of 1.46 per 100,000 (2). This rate of incidence translates to an estimated prevalence of 30,000 Myelofibrosis patients in the United States.

1. Ma X, Vanasse G, Cartmel B, Wang Y, Selinger HA. Prevalence of polycythemia vera and essential thrombocythemia.
2. Mesa R, Silverstein M, Jacobson, Wollan P, Tefferi A. Population-based incidence and survival figures in essential thrombocythemia and agnogenic myeloid metaplasia: an Olmsted county study, 1976-1995.