What is Essential Thrombocytosis?
Essential thrombocytosis, also known as essential thrombocythemia (ET), is a condition first identified in 1934. Back then, it was referred to as “hemorrhagic thrombocythemia”. Essential thrombocytosis belongs to a group of conditions known as myeloproliferative neoplasms, which were categorized as such in 1951 by Damesheck. Other conditions in this group include polycythemia vera and primary myelofibrosis. These conditions are similar as they all occur due to the same types of genetic changes. In fact, about 55% of people with essential thrombocytosis have a mutation in the JAK2 gene.
Essential thrombocytosis is defined by an increase in the number of platelets (tiny blood cells that help your body form clots to stop bleeding), alongside an increase in megakaryocytes (cells that produce platelets) in the bone marrow. With this increase in platelets, there may be risks of blood vessel related events, such as blood clots and bleeding, and sometimes, it can even change into a more serious condition known as myelofibrosis.
According to the World Health Organization, essential thrombocytosis is diagnosed when the platelet count exceeds 450,000 and there are mutations in certain genes (JAK2, Calreticulin or MPL) without any other known cause. This overview will explain the cause, occurrence rate, how the disease operates in the body, assessment, and treatment options for this condition.
What Causes Essential Thrombocytosis?
Essential thrombocythemia (ETT) is mainly caused by cells that are overproduced due to changes called mutations in certain genes – JAK2, CALR, or MPL. These genes are sometimes referred to as “driver mutations” because they can lead to a type of abnormal cell growth known as a myeloproliferative neoplasm.
Even though about 90% of adults with ETT have these gene mutations, children can sometimes have what’s known as a “molecular triple wild-type status” where none of these three genes have mutations.
The JAK2 gene mutation, specifically JAK2V617F, is found in approximately half of the people with ETT. Having two altered copies of this gene (what doctors call a homozygous mutation) can lead to more severe symptoms. One such complication could be an increased risk for Heparin-induced thrombocytopenia (HiT), a condition where blood clots form after exposure to a drug called Heparin.
CALR gene mutation is present in about a quarter of people with ETT. This gene mutation is often seen in younger patients, who have high platelet counts but a lower risk of blood clot formation.
MPL gene mutation, specifically MPLW515L/K type, appears in about 4% to 5% of people with ETT. This mutation is usually related to the transformation of cells into leukemia – a type of cancer.
There are also several other mutations and abnormal gene variants that can occur in people with ETT. These include changes in the SH2B3, SF361 (related to scarring in organs known as fibrosis), U2AF1 (associated with fibrosis and very high platelet counts), TP53 (predicts transformation into leukemia), IDH2, E2H2 (linked with extremely high platelet counts), 20q- (occurs in about 5% of ETT patients), and -Y (loss of the Y chromosome is linked with shorter survival).
Some mutations like those in the Gelsolin and JAK2V617I genes seem to be linked with familial formats, indicating they can be passed down in families. Certain genetic forms, such as the MPL (Ser505Asn) mutation, are found in particular geographic populations, like Italian families. It’s suggested that local clusters of high platelet counts (which is what thrombocytosis means) may exist and could be underdiagnosed, hence underestimated.
Risk Factors and Frequency for Essential Thrombocytosis
Essential thrombocytosis is a common blood disorder, and it is the leading type of condition known as myeloproliferative neoplasm. This condition affects between 1.0 to 2.5 people out of 100,000 each year. Interestingly, more women tend to have this disorder.
- The occurrence of essential thrombocytosis was noted to be between 38 to 57 per 100,000 from 2008 to 2010.
- The chance of having this disorder increases as we age, with most people being diagnosed between the ages of 50 and 60.
- Something to note is that newborns and babies can also have high platelet counts, especially if they were born with a low weight.
- Platelet counts of up to 600,000 per microliter are considered normal in these kids.
Signs and Symptoms of Essential Thrombocytosis
Essential thrombocytosis is a condition that can lead to a variety of symptoms. Some people with this condition may not show any symptoms, and the presence of an excessive amount of platelets in their blood (thrombocytosis) is often discovered by accident as part of a routine blood test. However, other patients may experience frequent fatigue (90% of cases), insomnia, migraines, headaches, and dizziness.
Additionally, these patients may also develop different degrees of thrombosis, which refer to blood clots in their veins. For example, they may experience hepatic vein thrombosis, a classic sign of this disease. Some patients may show symptoms like transient ischemic attacks (temporary interruptions of blood flow to parts of the brain), erythromelalgia (a rare condition that causes episodes of burning pain and redness in the feet or hands), and easy bruising.
The most commonly observed sign during a physical examination of patients with essential thrombocytosis is an enlarged spleen (splenomegaly), although the enlargement is typically mild compared to other similar conditions known as myeloproliferative neoplasms.
- Excessive amount of platelets (found during routine blood test in asymptomatic patients)
- Frequent fatigue
- Insomnia
- Migraines
- Headaches
- Dizziness
- Transient ischemic attacks
- Erythromelalgia
- Easy bruising
- Mildly enlarged spleen
Testing for Essential Thrombocytosis
The World Health Organization (WHO) has specific criteria for diagnosing Essential Thrombocythemia (ETT), a condition where you produce too many platelets. These blood cells help your blood clot, and too many of them can lead to blood clots and other complications. For a doctor to diagnose ETT, all four of the following major conditions must be met or the first three major and the minor ones:
Major Criteria:
- Your platelet count is 450,000/microliter or more. Platelets are a type of blood cell that helps with clotting.
- A bone marrow biopsy, which is a test where a small amount of your bone marrow is removed for examination, shows mainly increased preparation of megakaryocytes. These are cells in your bone marrow that produce platelets. Also, there shouldn’t be significant activity in the creation of white or red blood cells.
- Your symptoms don’t match any other blood disorders as per WHO criteria.
- There’s evidence of specific genetic markers, identified as JAK2, CALR, or MPL.
Minor Criteria:
There is a clonal marker present or there is no evidence of reactive thrombocytosis, which means the increased platelet count is not due to another condition like an infection, inflammation or cancer.
To diagnose ETT, patients would usually get a complete blood count, a bone marrow biopsy, and genetic testing. This is to check for any gene mutations causing the patient’s condition. The symptoms of different blood disorders can be similar, so it’s important to rule out other causes before diagnosing with ETT.
In children, ETT appears slightly differently. Many kids show no symptoms, although some might have enlarged spleen or liver. Therefore, other than lab tests, the child’s bone marrow biopsy and other analyses are especially important for diagnosis. Additionally, it’s helpful to know which genetic mutation a patient has – whether it’s JAK2, CALR, or MPL – because each mutation has different implications for disease characteristics, complications, and life expectancy. For instance, having the CALR mutation often means a better prognosis.
Treatment Options for Essential Thrombocytosis
Essential thrombocytosis is a condition that increases the risk of blood clots and bleeding, both of which can be dangerous. The main goal of treating this condition is to prevent these complications. A scoring system called the International Prognostic Score for Essential Thrombocytosis (IPSET) is used to identify risk factors and guide treatment.
Risk levels determine the treatment approach. Low-risk patients are usually under 60 years of age and haven’t had any blood clots before. High-risk patients are generally older than 60 and have had a history of blood clotting. For low-risk patients, one of the treatments can be aspirin unless they have certain conditions like a blood disorder known as acquired von Willebrand syndrome, which can cause bleeding problems. High-risk patients may receive a combination of low-dose aspirin and a type of medication that reduces blood cells (cytoreductive therapy).
Cytoreductive therapy involves drugs such as hydroxyurea, anagrelide, and interferon. Hydroxyurea is commonly used, and it works by reducing the number of blood clot-forming cells (platelets) and white blood cells, reducing the risk of blood clots and a condition called myelofibrosis, which is a serious bone marrow disorder. Anagrelide is another treatment used to lower the count of platelets, but it could increase the rate of bleeding when combined with aspirin.
Medical trials have shown that cytoreductive therapy can effectively reduce the number of blood-clot events. For example, one study revealed a significantly lower percentage of high-risk patients taking hydroxyurea experienced clot events compared to those not taking the drug.
In pregnant patients with essential thrombocytosis, the risk of complications, including early pregnancy loss and issues with the placenta, can increase. Treatment for these patients may include low molecular weight heparin and aspirin with careful monitoring for bleeding, and a treatment called pegylated interferon. Certain situations may also call for a procedure called plateletpheresis to quickly lower a high number of platelets. However, hydroxyurea and anagrelide should not be used during pregnancy due to risks to the fetus.
Other treatments have been tested but have issues or risks that limit their use. For instance, a drug known as busulfan is limited by its potential to transform into serious blood disorders, while other drugs have shown limited effectiveness or carry significant side effects.
Lastly, a symptom of essential thrombocytosis called Erythromelalgia, which causes painful and hot sensations in the feet or hands, can be treated with aspirin. However, using aspirin in children requires caution due to the rare but potentially fatal condition called Reyes syndrome, which can result in brain swelling and liver damage.
What else can Essential Thrombocytosis be?
Essential thrombocytosis is a condition where your body produces too many blood platelets. But there are other conditions that have similar symptoms, and doctors have to consider these before confirming a diagnosis of essential thrombocytosis. These conditions fall into a few categories:
- Clonal neoplasms – These are diseases that also cause your body to create too many blood cells. Examples of these conditions are polycythemia vera and primary myelofibrosis. These diseases have very similar symptoms, and the only way to tell them apart is by ruling out other conditions.
- Reactive or secondary thrombocytosis – This is when your platelet count increases in response to other conditions or events. For example, infections, inflammation like Kawasaki disease, tissue damage from surgery or injury, an underdeveloped spleen, iron deficiency anemia, cancer, certain drugs like vincristine, allergic reactions, and hemolysis (the breakdown of red blood cells) can all cause an increase in platelets. COVID infections can increase this risk even more if someone already has a condition that raises platelet production.
- Spurious thrombocytosis – This is when platelet counts appear high because the automated counting machines in labs mistake other things like cryoglobulin crystals, pieces of leukemia cells, and bacteria for platelets.
- Hereditary or Familial Thrombocytosis – This is a genetic condition where the body naturally produces more platelets than normal. It often shows up with symptoms like hepatosplenomegaly (enlargement of the liver and spleen) and increased platelet activation. The genes affected usually involve the TPO gene or its receptor MPL, and there are an excess of megakaryocytes (the cells that produce platelets) in the bone marrow.
In each of these conditions, it’s important for doctors to use cautious judgement and thorough testing before making a diagnosis.
What to expect with Essential Thrombocytosis
Essential thrombocytosis is a slow-progressing medical condition with a median survival time of 18 years. In simpler terms, this means that half of the people with this condition live more than 18 years after their diagnosis. For patients who are younger than 60 when diagnosed, life expectancy can even reach up to 33 years. Interestingly, when compared to a similar condition called polycythemia vera, individuals with essential thrombocytosis usually have a longer life expectancy.
However, even though essential thrombocytosis progresses slowly, it’s important to note that the life expectancy for patients with this condition is still generally lower than that of the overall population. This is largely due to the risk of complications such as thrombotic events – medical speak for dangerous blood clots – that can cause serious problems.
Possible Complications When Diagnosed with Essential Thrombocytosis
The main health risk associated with a condition called essential thrombocytosis, is thrombosis, which is a blood clot that forms in your blood vessels. This happens about 20% of the time. The second most common risk is hemorrhage, or uncontrollable bleeding, which happens in about 10% of cases. However, the chances of the condition developing into something more serious are less than 1%.
Blood clots can occur in different places in the body. If they form in the brain, they can cause a transient ischemic attack or a stroke. If they form in the heart vessels, it can lead to a condition known as acute coronary syndrome. And if they occur in the liver veins, it can lead to a condition called Budd-Chiari syndrome.
People over the age of 60 who have had a blood clot before are the most at risk for another blood clot. Children are at a much lower risk for both blood clots and uncontrollable bleeding.The chance of the disease turning into leukemia is very rare in children but can be between 2% to 5% in adults over a period of 10 to 15 years.
Additionally, it’s important to mention that essential thrombocytosis can lead to complications during pregnancy, including high blood pressure in pregnancy (eclampsia), premature separation of placenta from the uterus (placental abruption), slow growth of the baby in the uterus, and stillbirth.
Health Risks:
- Thrombosis (Blood clots) – 20%
- Hemorrhage (Uncontrollable bleeding) – 10%
- Brain blood clots resulting in transient ischemic attack or stroke
- Heart vessel blood clots resulting in acute coronary syndrome
- Liver vein blood clots resulting in Budd-Chiari syndrome
- Increased risk of blood clots for people older than 60 with history of blood clots
- Lower risk of blood clots and uncontrolled bleeding in children
- Potential leukemia risk in adults (2% to 5% over 10 to 15 years)
- Possible pregnancy complications (eclampsia, placental abruption, slow growth of baby, stillbirth)
Preventing Essential Thrombocytosis
Essential thrombocytosis, a condition where your body produces too many platelets, can’t be cured. But remember, taking your prescribed medicines consistently can help manage the condition and prevent further complications. It’s also crucial to keep track of your health by having regular check-ups so your doctor can closely monitor your platelet levels. If your platelet count is extremely high, your doctor might recommend a medicine called hydroxyurea to reduce the risk of thrombosis, which is the forming of harmful blood clots. So, keeping an eye on your platelet count is really important.