An Overview of Essential Thrombocythemia and Abnormal Blood Clotting

Essential thrombocythemia (ET) is a rare disorder in which the bone marrow produces too many platelets. ET is part of a category of diseases known as myeloproliferative disorders, a group of disorders characterized by the increased production of a particular type of blood cell.

Platelets are the cells responsible for blood clotting which literally stick together at the site of a laceration or injury in order to stop bleeding. In persons with ET, the presence of excessive platelets can be problematic, causing the abnormal formation of clots inside a blood vessel (a condition known as thrombosis).

While the specific cause of ET is unknown, around 40 to 50 percent of people with the disorder have a genetic mutation known as the JAK2 kinase. Other clonal mutations sometimes seen involve the calreticulin and MPL genes. ET is an extremely uncommon disorder, affecting fewer than three out of 100,000 people per year. It affects women and men of all ethnic backgrounds but tends to be seen more in adults over 60.

People with essential thrombocythemia are often diagnosed after developing specific symptoms related to a blood clot, which may be venous or arterial. Depending on where the clot is located, symptoms may include:

• Headache
• Dizziness or lightheadedness
• Weakness
• Livedo reticularis (a characteristic skin rash)
• Fainting
• Chest pains
• Changes in vision
• Numbness, redness, tingling, or a burning sensation in the hands and feet
• Higher risk of bleeding

Less commonly, abnormal bleeding can develop as a result of ET. While low platelet counts can cause bleeding due to the lack of clotting, excessive platelets can have the same effect as the proteins needed to stick them together (called the von Willebrand factor) may be spread too thin to be effective. When this happens, abnormal bruising, nosebleeds, bleeding from the mouth or gums, or blood in the stool may occur.

The formation of blood clots can sometimes be serious and potentially lead to heart attack, stroke, transient ischemic attack (a "mini-stroke"), or digital ischemia (loss of blood flow to a finger or toe). An enlarged spleen is also seen in around 28 to 48% of cases due to the obstruction of blood circulation.

Additional complications include an increased risk of pregnancy loss and other complications of pregnancy in people with ET. People with ET additionally have an increased risk of developing myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML).

Essential thrombocythemia is often spotted during a routine blood exam in persons who either have no symptoms or vague, nonspecific symptoms (such as fatigue or a headache). Any blood count of over 450,000 platelets per microliter is considered a red flag. Those over a million per microliter are associated with a higher risk of abnormal bruising or bleeding.

A physical exam may reveal a spleen enlargement characterized by pain or fullness in the left upper abdomen that may spread to the left shoulder. Genetic testing may also be performed to detect the JAK2, calreticulin and MPL mutations.

The diagnosis of ET is largely exclusionary, meaning that any other cause for the high platelet count must be first excluded in order to make a definitive diagnosis. Other conditions associated with a high platelet count include polycythemia vera, chronic myeloid leukemia, and myelofibrosis.

The treatment of essential thrombocythemia depends largely on how elevated the platelet count is as well as the likelihood of complications. Not all people with ET require treatment. Some simply need to be monitored to ensure the condition doesn't worsen.

If needed, treatment may involve a daily low-dose aspirin for those considered to be at higher risk for bleeding (based on older age, medical history, or lifestyle factors such as smoking or obesity), or for lower-risk patients who have vasomotor symptoms (signs of blood vessel dilation and constriction).

Drugs such as hydroxyurea are often used for platelet counts above 1 million to help reduce the platelet levels. Other medications that might be prescribed include anagrelide and interferon-alpha.

In an emergency, plateletpheresis (a process in which blood is separated into its individual components) may be performed to quickly reduce the platelet count. However, this is a short-term solution that is typically followed by the use of medication to lower the platelets to less than 400,000.