Essential Thrombocythaemia

Essential thrombocythaemia is a rare blood disorder where your bone marrow produces too many platelets, leading to an increased risk of blood clots, heart attack, or stroke—yet with proper treatment, most people live a nearly normal life.

Table of contents

• What is essential thrombocythaemia?
• Medical identification codes and synonyms
• What causes essential thrombocythaemia?
• Who is affected by this condition?
• How does this condition affect your body?
• Signs and symptoms
• How is essential thrombocythaemia diagnosed?
• Treatment and management
• Outlook and prognosis
• Living with essential thrombocythaemia

What is essential thrombocythaemia?

Essential thrombocythaemia, also known as essential thrombocythemia (ET) or primary thrombocythemia, is a rare blood disorder that happens when abnormal stem cells in your bone marrow make too many platelets^[1]. Platelets are blood cells that slow or stop bleeding by creating blood clots. This condition belongs to a group of blood disorders called myeloproliferative neoplasms, which are blood cancers that happen when your body produces too many blood cells^[1].

Essential thrombocythaemia was first described in 1934 and was initially termed hemorrhagic thrombocythemia^[4][5]. The condition is characterized by a sustained elevation of platelet numbers, typically with platelet counts exceeding 450,000 per microliter of blood^[4]. Your bone marrow examination reveals an increase in the number of megakaryocytes, which are the large cells that produce platelets, along with enlarged, mature megakaryocytes^[4].

Essential thrombocythaemia is an acquired genetic condition, meaning it happens when certain genes mutate or change during your lifetime^[1]. It is not usually inherited from parents, though there may be a familial tendency to develop the disease in some patients^[2]. You may learn you have this condition when a routine blood test shows your platelet levels are unusually high. Many people with ET have no symptoms at the time of diagnosis^[1].

Medical identification codes and synonyms

Primary thrombocythemia, Hemorrhagic thrombocythemia, ET

What causes essential thrombocythaemia?

No one knows what causes the onset of essential thrombocythaemia or other myeloproliferative neoplasms^[2]. However, researchers have discovered mutations that alter the activity of proteins that control signaling pathways, which are important regulators of cell growth and development in many patients with ET^[2].

The most common genetic change found in people with essential thrombocythaemia is a mutation in the JAK2 gene, which occurs in approximately 50 to 60 percent of patients^[2][7]. This mutation, called JAK2 V617F, leads to hyperactive JAK (Janus kinase) signaling, causing the body to make the wrong number of blood cells^[2]. The mutation results from a change where valine is substituted with phenylalanine at a specific position in the gene^[7].

Other genetic mutations associated with essential thrombocythaemia include^[2][7]:

• CALR (Calreticulin) mutations, which occur in approximately 23.5 percent of patients with ET. These mutations are caused by insertions or deletions resulting in a reading frame shift and the formation of a new protein ending
• MPL mutations, found in up to 5 percent of cases. These point mutations in the myeloproliferative leukemia virus gene lead to increased sensitivity to thrombopoietin, the hormone that controls platelet production

These mutations cause constant activation of the JAK/STAT and other signaling pathways, as well as increased sensitivity to thrombopoietin, resulting in uncontrolled platelet production^[7]. Approximately 10 to 20 percent of patients do not have any of these common mutations^[5].

Some risk factors have been identified that may be associated with developing essential thrombocythaemia. These include working in agriculture and petroleum refineries, benzene exposure, and smoking^[7].

Who is affected by this condition?

Essential thrombocythaemia is a rare disease. It affects about 2 in 100,000 people in the United States^[1]. The incidence is estimated at 1.5 to 2 individuals per 100,000 annually^[12]. The prevalence in the general population is approximately 30 per 100,000^[6].

This condition affects twice as many women as men^[1]. Women are 1.5 times more likely than men to develop essential thrombocythaemia^[2]. Most commonly, it is diagnosed in women over the age of 50^[2].

Essential thrombocythaemia typically affects people between age 60 and 80, with the median age at diagnosis being 65 to 70 years^[1][6]. However, about 20 percent of all cases involve people age 40 and below^[1][2]. A second peak of diagnosis has been noted at about 30 years, and the majority of those diagnosed at this age are female, raising important management issues in this group at child-bearing age^[12].

Children rarely have this condition, and when they do, it is because they inherited it from a biological parent^[1].

How does this condition affect your body?

Essential thrombocythaemia affects your platelets, the tiny, sticky blood cells that are first on the scene if your blood vessels break from injury or disease. Because platelets are sticky, they quickly form clumps that literally plug holes in damaged blood vessels^[1].

Your bone marrow produces platelets along with red and white blood cells. Normally, your bone marrow acts like a factory supervisor, carefully monitoring supply and demand so you have just enough platelets on hand to slow or stop bleeding. In essential thrombocythaemia, however, your bone marrow produces more platelets than your body needs. The abnormal platelets are also larger than normal and oddly shaped^[1].

Like excess inventory that takes up space in already-crowded storage areas, the abnormal platelets make blood clots that crowd into blood vessels and block blood flow^[1]. Essential thrombocythaemia can cause blood clots anywhere in your body, especially in your brain, hands, and feet^[1]. The main risks for people with ET are arterial and venous blood clots, as well as temporary blockages of tiny blood vessels and bleeding^[6]. Blood clots in large arteries represent a major cause of death associated with ET or can cause severe problems affecting the brain, heart, or leg arteries^[6].

This condition may also cause unusual or excessive bleeding. That may sound odd since essential thrombocythaemia usually makes your blood clot, or stop flowing. In this situation, unusual or excessive bleeding happens because the dramatic increase in blood clots uses up platelets in your bloodstream, leaving you without platelets to slow or stop bleeding^[1]. Extreme elevation in platelet counts may promote the abnormal absorption of large von Willebrand factor molecules, which can lead to acquired von Willebrand disease and bleeding problems^[9].

Women who are pregnant or planning to become pregnant have additional risk of developing blood clots during pregnancy^[1]. People with essential thrombocythaemia may have increased risk of a heart attack or a stroke^[1].

Less common consequences in the later stages of ET include transformation to myelofibrosis (scarring of the bone marrow) or acute leukemia^[2]. However, these represent only rare and frequently later-onset events^[6]. Life expectancy is almost normal and similar to that of a healthy population matched by age and sex^[6].

Signs and symptoms

Many people with essential thrombocythaemia have no symptoms. Consequently, the disease is often diagnosed as part of a routine check-up, after a blood test reveals a high platelet count^[2]. When symptoms are present, they may include fatigue, or may be related to small or large blood vessel problems or bleeding^[2].

The clinical picture is dominated by a tendency toward blood vessel blockages affecting various parts of the body, including the brain, heart, and leg circulation, as well as bleeding episodes^[6]. Some patients with ET experience a range of symptoms, including^[6]:

• Vasomotor symptoms (symptoms related to blood vessel function): headaches, visual disturbances, lightheadedness, atypical chest pain, unusual sensations in the hands or feet, and a burning pain in the hands and feet called erythromelalgia
• Problems related to blood clots
• Bleeding episodes

Common symptoms related to small blood vessel disturbances may include^[2]:

• 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

When bleeding is present as a symptom of essential thrombocythaemia, it can show up as^[2]:

• Easy bruising, nosebleeds, or heavy periods
• Gastrointestinal bleeding or blood in the urine

Blood clot complications can also occur and may affect various parts of the body^[2]. Looking back, some people realize they had been experiencing symptoms related to ET for years before being diagnosed, though they didn’t recognize these as signs of a medical condition at the time^[15].

Some patients may also experience increasing long bone pain, numbness on the scalp, ears, and face, and a burning, tingling feeling, as if someone had lit small sparklers all over the body^[15].

How is essential thrombocythaemia diagnosed?

Essential thrombocythaemia is often suspected after a routine blood test shows that a patient has a high platelet count^[2]. You may also consult a doctor after experiencing one or more symptoms of ET^[2].

Diagnosis relies on World Health Organization criteria and requires ruling out other causes of high platelet counts, known as reactive thrombocytosis^[4]. If you have essential thrombocythaemia, you have a high platelet count that is not related to another medical condition. If you have reactive thrombocytosis, your platelet count is high because you have another disease or condition. Reactive thrombocytosis is more common than essential thrombocythaemia^[1].

Based on diagnostic tests and a review of patient history and symptoms, a doctor can determine whether a patient has ET and whether the case can be categorized as having low or high risk^[2].

Common tests for diagnosing essential thrombocythaemia

Blood tests are the first step in diagnosis. A blood test called a complete blood count (CBC) can show if your platelet count is too high^[11]. Blood tests can also rule out other causes of a high platelet count. This often includes tests for iron deficiency and signs of inflammation, as well as other blood diseases that might look similar^[2].

Gene mutation analysis of blood cells is an important part of diagnosis. Doctors may test for gene mutations like JAK2 (occurring in approximately 50 percent of cases), CALR (occurring in 23.5 percent of cases), or MPL (occurring in up to 5 percent of cases)^[2]. You may also need blood tests to check for high or low iron levels, markers of inflammation, undiagnosed cancer, and gene mutations^[11].

A bone marrow biopsy may be done to look for typical signs of ET, such as an increase in platelet-producing cells, or to rule out an early phase of myelofibrosis^[2]. This procedure uses a needle to remove a small sample of your bone marrow for testing^[11]. Bone marrow examination reveals an increase in megakaryocytes with enlarged, mature forms^[4].

Treatment and management

Essential thrombocythaemia is not curable but treatment may reduce the risk of developing serious complications^[1]. Treatment for essential thrombocythaemia aims to manage the effects of the disease rather than cure it. The goal is to lower your platelet count, which lowers your risk of blood clots that can cause heart attack or stroke^[13].

Treatment should be tailored to each individual based on risk factors for blood clots or bleeding^[5]. Your doctor will decide on your treatment based on your personal circumstances. They will consider your age, your level of risk for blood clots, and the number of platelets in your blood^[13].

Risk factors for complications

Risk factors that doctors consider include^[9]:

• Age 60 years or older
• History of blood clots
• Platelet count greater than 1,500,000 per microliter, which is linked with an increased risk of gastrointestinal bleeding in young women
• Obesity
• Heart and blood vessel risk factors such as smoking, high blood pressure, and high cholesterol
• Markers of increased blood clotting tendency
• JAK2 or MPL mutation

Lifestyle changes should be recommended for all patients with reversible risk factors. These include diet and exercise to promote weight loss for people who are overweight, and stopping smoking for smokers^[9].

Treatment approaches based on risk level

People with essential thrombocythaemia who have no signs or symptoms usually do not need treatment right away^[11]. For very low-risk patients (those lacking any risk factors), observation may be appropriate, although once-daily aspirin may be used in those with heart and blood vessel risk factors or symptoms^[9].

Low-risk patients (those whose only risk factor is JAK2 or MPL mutation) can be treated with daily low-dose aspirin therapy^[9]. You might need to take daily, low-dose aspirin to help thin your blood if you are at risk of blood clots^[11]. Low-dose aspirin is a common treatment that helps to lower the number of platelets in the blood^[10]. However, aspirin should be used carefully or not at all in patients with certain bleeding disorders^[9].

Intermediate-risk patients may benefit from both aspirin and medicines that reduce platelet production. Selection of treatment should be tailored based on factors including symptom severity, heart and blood vessel risks, and patient preference^[9].

High-risk patients benefit from both aspirin and medicines that reduce platelet production^[9]. You might need to take prescription medicine or have procedures to lower your platelet counts if you have a history of blood clots and bleeding, risk factors for heart disease, are older than 60, or have a very high platelet count^[11].

Medicines to reduce platelet production

Hydroxycarbamide (also called hydroxyurea) is the most common type of medicine used to treat ET^[10]. This is a type of chemotherapy that uses cell-killing drugs to destroy the extra platelets. The drugs work by disrupting the growth of cells and stopping them from dividing. You take it as a tablet^[10]. The helpful value of hydroxycarbamide and aspirin in high-risk patients has been supported by controlled studies^[6]. There may be a small increase in the risk of developing leukemia if you take this for a long time^[10].

Anagrelide is another medicine that can be used. Avoiding drugs that reduce platelet production or choosing anagrelide to delay the long-term side effects of hydroxycarbamide in young or low-risk patients represent alternative options^[6].

Busulfan is another type of chemotherapy usually used in older people who cannot take hydroxycarbamide. Research shows it increases the risk of developing leukemia if taken for long periods, so you might take it for a while and then stop for a period before starting again^[10].

Interferon medicines, particularly peginterferon alfa-2a, may also be used in certain situations^[9][10].

In emergencies, a procedure called plateletpheresis may be useful to achieve a rapid decrease in platelet counts in the setting of acute blood clots or very high platelet counts^[9].

All the treatments can be taken at home and incorporated into your daily routine^[13]. You may stay on the same treatment for a period of years. Your doctor will consider a new treatment if the one you are having stops working as well or causes serious side effects^[13].

Special situations

Generally, surgery or pregnancy is not associated with significantly increased blood clot or bleeding risk in low-risk patients^[9]. However, women who are pregnant or planning to become pregnant need special consideration due to additional risks of developing blood clots during pregnancy^[1].

Outlook and prognosis

Although considered a slowly progressing disease, ET carries significant health risks, including arterial and venous blood clots, bleeding, and potential transformation to myelofibrosis or acute leukemia^[4]. Lifespan may be shortened due to these complications^[4].

However, life expectancy is almost normal and similar to that of a healthy population matched by age and sex^[6]. Compared with other myeloproliferative disease types, ET has a favorable overall outlook, though the overall survival rate remains lower compared with the general population^[7].

Acute leukemia or bone marrow problems represent only rare and frequently later-onset events^[6]. Some people with essential thrombocythaemia may develop leukemia, but this is not common^[1].

Patient education plays a key role in improving adherence to treatment and reducing harmful events related to blood clot and bleeding risks^[4].

Living with essential thrombocythaemia

Having a support system is vital for someone with an MPN, as this can be an isolating condition^[15]. One of the challenges of living with essential thrombocythaemia is that people with this condition never look sick on the outside. Most people do not even recognize what someone with ET is going through, because nothing looks different. This means people may forget that you have a chronic condition^[15].

Many of the symptoms, such as fatigue, dizziness, and shortness of breath, sound common. When people with ET complain about their symptoms, others often say they experience the same things. However, normal tiredness is very different from the overwhelming, exhausting fatigue of someone with an MPN^[15].

For the most part, people with ET try not to let the condition stop them. There are two choices: let it stop you and lie on the couch, or keep moving. Usually, it is better to keep moving^[15].

Having a community of support is important. There is a lot of help available for more common forms of cancer, but less for ET. People who do not have an MPN, even those with other kinds of cancer, do not truly understand what it is like to live with an MPN. That is why it is wonderful to talk with people who have the same symptoms, the same challenges, and the same goals^[15].

Connecting with other people who have the condition can be helpful. Patient support groups and online communities exist where people can share their symptoms or ask questions to others going through the same experiences. Attending patient education meetings can also provide opportunities to meet others with ET and build lasting connections^[15].