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Essential thrombocythemia

This page was reviewed under our medical and editorial policy by

Maurie Markman, MD, President, Medicine & Science at CTCA.

This page was updated on November 3, 2022.

Essential thrombocythemia (ET), also known as primary thrombocytosis, is a rare type of blood cancer in which cells in the bone marrow produce too many blood-clotting components called platelets. The disease affects between 0.6 and 2.5 cases per 100,000 Americans yearly, according to the National Cancer Institute, and between 1 and 24 cases per 1 million people globally, according to the U.S. National Library of Medicine.

This article will provide provide an overview of essential thrombocythemia, covering these topics:

What is essential thrombocythemia?

ET is a subset of myeloproliferative neoplasms (MPN), which begin with changes to the genetic code of stem cells that then develop into many types of blood cells. These cells live in the bone marrow, the spongy tissue inside some bones. Because MPNs start with one genetically deformed cell, they’re classified as clonal diseases. Other MPNs include polycythemia vera, primary myelofibrosis (MF) and certain chronic leukemias.

Essential thrombocythemia is caused by specific gene mutations in blood stem cells. These cells make blood cells called megakaryocytes, which create platelets. Platelets are small cell fragments in the blood that stick together to help stop bleeding by forming clots around wounds. In ET, too many platelets are made in the bone marrow.

The excess number of platelets in ET leads to complications. The biggest risk is that blood clots will build up and lead to a heart attack, stroke or pulmonary embolism. Other complications include bleeding and swelling in the hands and feet.

ET is also known as primary thrombocytosis because it results directly from changes in blood stem cells. Secondary thrombocytosis occurs when a high platelet count is caused by other conditions that don’t change the blood stem cells—like inflammatory disease, iron deficiency or spleen removal. If the cause of the high platelet count is addressed, the platelet count should return to normal in secondary thrombocytosis.

Essential thrombocythemia symptoms

According to the National Cancer Institute, when ET first develops, about half of patients don’t experience symptoms. Instead, the condition is often discovered during routine blood testing. The asymptomatic phase may last for years, and some people go for long periods without knowing they have the disease.

Common symptoms of ET include:

  • An enlarged spleen (splenomegaly), which may lead to a feeling of pressure or fullness below the ribs on the left side
  • Headaches
  • Vision or hearing problems
  • Burning, tingling or prickling of the skin
  • Swelling, pain, redness and warmth in the hands and feet

Other symptoms related to increased blood clotting, increased bleeding or other complications included those below.

Essential thrombocythemia causes and risk factors

ET often develops spontaneously during adulthood. Genetic mutations occur in the cells of the bone marrow, though researchers don’t know the specific factors that cause them.

Middle-age people are at greater risk for developing ET. However, ET is also seen in younger people–usually women under age 40.

The main types of mutations found in ET are those to the JAK gene and the CALR gene. According to the American Journal of Hematology, mutations in JAK2, CALR and MPL are responsible for 55 percent, 25 percent and 3 percent of new ET cases, respectively.

However, up to 20 percent of cases of ET have no identified gene mutations, according to the American Journal of Hematology. These are called “triple-negative” cases of ET.

JAK/STAT - mutations in JAK2, MPL and THPO

One of the main causes of ET is mutations in the JAK/STAT signaling pathway in blood stem cells. When activated, the JAK/STAT pathway tells these cells to grow, divide and create more megakaryocytes, which make more platelets.

The JAK2, MPL and THPO genes are all a part of this pathway. Mutations in these genes result in the pathway being turned on or activated inappropriately, which may lead to ET.

CALR and others

The CALR gene codes for a protein called calreticulin, which is important in helping new proteins form properly in cells. It also plays a role in maintaining calcium storage levels.

Another mutated gene linked to ET is the TET2 gene, though researchers aren’t sure how these mutations are related to the development of the disease.

Familial essential thrombocythemia

In rare cases of ET, the disease is inherited from a family member in an autosomal dominant manner. This means the disease is inherited via an abnormal gene from one parent. Those who have a copy of an autosomal dominant gene mutation have a higher risk of developing ET and of passing that risk to their kids. This condition is called familial essential thrombocythemia.

Research has suggested that some inherited cases of thrombocythemia may lead to a higher risk of thrombotic events but don’t necessarily increase the risk of post-ET myelofibrosis (MF) or leukemia.

How is essential thrombocythemia diagnosed?

An ET diagnosis requires many tests. The doctor starts by taking a detailed medical history and physical exam, and will then order blood and lab tests, including a genetic test.

In cases of ET, a complete blood cell count (CBC) test shows a count above 450,000 platelets per microliter (μL). Typical platelet values range from about 150,000 to 400,000 platelets per μL.

On a peripheral blood smear, platelets may appear enlarged or clumped together in ET patients.

Patients with high platelet counts may be tested for a bleeding disorder known as acquired von Willebrand syndrome (AVWS), which leads to excessive bleeding because too many platelets impair the body’s natural process to stop bleeding.

The genetic test will check for mutations in the JAK2, MPN, THPO, CALR or TET2 genes.

A bone marrow biopsy may be performed but isn’t required to diagnose ET. During a bone marrow biopsy, a sample is taken of the spongy tissue inside the bones. Bone marrow testing can be performed at a doctor's office or a hospital.

In ET, the bone marrow has many megakaryocytes, which may be large and mature or appear abnormal in shape and size.

Treatment for essential thrombocythemia

ET patients are grouped into four basic risk categories that influence treatment recommendations:

  • Very low risk
  • Low risk
  • Intermediate risk
  • High risk

These categories are based on:

  • Age (older or younger than 60)
  • History of clotting events
  • Types of mutations

Patients in the very low risk group often require only observation, without the need for medications.

Medicines used to treat ET include aspirin and drugs that reduce the number of blood cells produced.

Taking a low dose of aspirin once (or potentially twice) a day may reduce the risk of blood clots, because aspirin stops platelets from sticking together. Patients in the low-risk, intermediate-risk and high-risk groups often take this therapy.

In cases where aspirin isn’t enough and the platelet count is too high, doctors will recommend other medications to reduce the number of blood cells being produced in the bone marrow, in a procedure called cytoreductive treatment. Patients in the intermediate and high-risk groups may be candidates for this therapy.

The first line of cytoreductive treatment is hydroxyurea (Hydrea®) to reduce the platelet count.

In emergency situations, ET patients may need to quickly reduce their platelet count through a procedure called plateletpheresis, to reduce clotting risk. A machine removes blood from the body to remove a portion of the platelets before returning the blood to the body. This process temporarily reduces platelets in the blood.

Complications of essential thrombocythemia

There are three types of complications that may come with ET:

  • Excessive clotting, leading to thrombotic events
  • Excessive bleeding
  • Progression to post-ET MF or leukemia

Clotting events

Some of the major complications of ET are due to the increased clotting of the blood, or thrombotic events. They include:

Deep vein thrombosis: A clot develops in the deep veins of the arm or leg, causing pain, swelling and redness in the affected limb.

Pulmonary embolism: A clot gets lodged in the lungs and cuts off blood supply, leading to shortness of breath, chest pain and cough.

Myocardial ischemia or heart attack: A clot cuts off blood supply to the heart muscles, causing chest pain, shortness of breath and nausea.

Ischemic stroke and transient ischemic attacks: A clot blocks the blood supply to the brain, leading to headaches, dizziness, weakness or numbness on one side of the body, blurred or double vision, and slurred speech.

These thrombotic events occur in more than 20 percent of ET patients, according to the American Journal of Hematology. They’re more likely in patients with other high risk factors, including:

  • Age (highest risk is for those over 60 years old)
  • History of clotting events
  • High blood pressure (hypertension)
  • Diabetes
  • Tobacco use
  • Other cardiovascular risk factors
  • An elevated white blood cell count
  • A JAK2V617F mutation

Bleeding

A potential problem of too many platelets is excessive bleeding. Called acquired von Willebrand syndrome, too many platelets may impair the body’s natural process to stop bleeding. Symptoms may include:

  • Nosebleeds
  • Bleeding in the gastrointestinal tract or bloody stools
  • Easy bruising
  • Bloody urine

Progression to leukemia and post-ET MF

In rare cases, ET may develop into leukemia. After having ET for 20 years, the patient’s risk of developing leukemia is around 5 percent, according to the American Journal of Hematology.

Post-ET MF occurs when the overproduction of cells damages the bone marrow, turning it fibrotic. The bone marrow produces fewer blood cells when it reaches this stage. Symptoms of post-ET MF include:

  • Loss of more than 10 percent of body weight in six months
  • Excessive sweating at night
  • Unexplained fever above 99.5 degrees
  • Swelling of the spleen
  • Anemia
  • High levels of lactate dehydrogenase (LDH) in the blood

Essential thrombocythemia life expectancy

According to the National Cancer Institute, the median survival for patients with ET is 10 to 15 years. Survival rates are estimates based on older data and treatments. Each individual is different, and advances in medicine may impact these estimates. ET is often diagnosed later in patients around 50 to 60 years old.

Factors that impact survival rate include:

  • JAK2/MPL mutations, which increase the risk of a clotting event
  • MPL mutations, which increase the risk of post-ET MF
  • Age
  • History of clotting
  • Scarring in the bone marrow

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