Essential Thrombocythemia Causes & Symptoms

Essential thrombocythemia is a rare form of cancer in which the body produces too many blood platelets. An overproduction of platelets may lead to an individual having thicker blood. 

Essential thrombocythemia is typically the result of a genetic mutation of either the JAK2 or CALR gene. What causes the mutation is unknown.

While most patients with ET don’t experience symptoms, the condition may lead to blood clots, fatigue, or even more severe complications. This article looks at the potential cause of essential thrombocythemia along with the symptoms someone with the disease may experience. 

Causes of Essential Thrombocythemia

Essential thrombocythemia is a type of myeloproliferative neoplasm (MPN). In MPNs, blood-producing cells in the bone marrow develop and reproduce excessively. 

In the case of ET, the body excessively produces platelets, particles in the blood that help form blood clots. The excess platelets result from ET causing the body to overproduce megakaryocytes, the precursor cells to blood platelets.

While we don’t yet understand what causes essential thrombocythemia, research has found that about 90% of people with ET have a gene mutation that contributes to the disease. 

Genetic Mutations Causing Essential Thrombocythemia

The mutations of the JAK2 and CALR genes are the two most commonly mutated genes found in patients with essential thrombocythemia. MPL, THPO, and TET2 are other gene mutations in ET patients. 

JAK2 Mutation in Patients with Essential Thrombocythemia

The JAK2 gene, also known as Janus Kinase 2, mutation in patients with essential thrombocythemia, occurs over the course of a person’s lifetime and is only present in certain cells. This type of mutation is known as a somatic mutation. 

There are two different mutations of the JAK2 gene commonly linked with ET:

• V617F
• Exon 12

The V167F mutation occurs in approximately 50% of people with ET. In this mutation, the amino acid, also known as the protein building block, replaces the caline with phenylalanine at position 617 in the protein. As a result, this mutation produces a JAK2 protein that is always activated, causing the body to overproduce megakaryocytes and, ultimately, blood platelets.

Exon 12 mutations are rare and usually found in younger individuals. Unfortunately, due to their rarity, exon 12 mutations need to be further studied to understand their impact on ET. 

“That was really the watershed moment—that discovery of the JAK2 mutation.”

– Dr. Ruben Mesa | Read about the latest essential thrombocythemia treatments

CALR Mutation in Patients with Essential Thrombocythemia

The CALR Gene, also known as calreticulin, is a somatic mutation in people with ET. CALR is found in many portions of the body, including the endoplasmic reticulum. CALR plays a role in:

• Control of gene activity
• Cell growth, division, and movement
• Attachment of cells to one another
• Regulation of cell death

In patients with essential thrombocythemia, mutations to the CALR gene are associated with a region known as exon 9. This mutation produces altered calreticulin protein with a different set of amino acids on one end. However, it is unclear how the changes lead to ET.

MLP, THPO, & TET2 Mutations in Patients with Essential Thrombocythemia

Less is known about the remaining genetic mutations linked with essential thrombocythemia. Mutations of the MPL and THPO genes impact patients with ET similarly to the JAK2 mutation. They both affect the JAK pathway, which signals the body to overproduce megakaryocytes. 

The TET2 gene produces a protein whose function is not known. Therefore, the mutation of the gene’s impact on patients with ET is also unknown.

What Causes Secondary Thrombocythemia?

Secondary thrombocythemia presents similar symptoms to essential thrombocythemia but is differentiated from ET because of the cause. Secondary thrombocythemia is caused by a disorder that triggers the increased production of normal platelet-forming cells. In contrast, essential thrombocythemia (or primary thrombocythemia) is caused by a disorder in the platelet-forming cells themselves. Therefore, essential thrombocythemia is classified as an MPN, while secondary thrombocythemia is not. 

There are several potential causes of secondary thrombocythemia. Some of the more common causes include:

• Excessive bleeding
• Spleen removal or other surgical procedures
• Infections
• Iron deficiency
• Hemolytic anemia
• Other forms of cancer
• Infections
• Trauma

Symptoms of Essential Thrombocythemia

Often people with essential thrombocythemia don’t experience any noticeable symptoms. In fact, many people don’t even discover that they have ET until they go in for routine blood work. 

The main concern of essential thrombocythemia is an increased risk of blood clots due to the thickening of the blood. The signs and symptoms linked with ET are common to those connected with signs of a blood clot and include:

• Numbness or tingling of the hands and feet
• Headache
• Chest pain
• Fainting
• Tiredness 
• Dizziness or lightheadedness

Symptoms may vary based on where potential blood clots are forming in your body. In addition, in rare cases, essential thrombocythemia may cause bleeding and result in:

• Bloody stool
• Bruising
• Nosebleeds
• Bleeding from your gums

According to Mayo Clinic, unusual bleeding is more likely to occur when a patient’s platelet count is more than 1 million platelets per microliter of blood. 

Complications of Essential Thrombocythemia

Even though essential thrombocythemia doesn’t typically result in many symptoms, monitoring the disease closely is crucial as it can go south in a hurry. In addition, the following complications are potentially life-threatening and can result from ET if the condition goes untreated. 

Strokes 

A stroke happens when a blood clot occurs in an artery that supplies the brain with blood. Since patients with ET are at high-risk for blood clots, it’s essential to monitor for signs of a stroke. 

Signs and symptoms of a stroke include:

• Numbness in your face, arm, or leg that is typically confined to one side of the body
• Difficulty speaking or understanding speech
• Blurred or decreased vision

If you feel the onset of a stroke, it is vital to seek medical attention immediately.

Heart Attacks

Although it is less common in those with essential thrombocythemia, heart attacks are a potential complication. A heart attack occurs when a blood clot blocks the blood supply to your heart. Sings of a heart attack include:

• Pressure in your chest lasting more than a minute
• Pain extending to your shoulder, arm, back, jaw, or teeth
• Difficulty breathing
• Sweat or clammy skin

Further Bone Marrow Issues

In rare cases, essential thrombocythemia can progress into a more serious disease of the bone marrow, including acute myelogenous leukemia or myelofibrosis.

When Should I See a Doctor?

You should visit a doctor if you are experiencing any symptoms or complications linked to essential thrombocythemia. While your diagnosis may not be ET, the above symptoms indicate that there is a potential issue.