Introduction

A great deal of people have essential thrombocythemia (ET) and feel completely healthy without knowing that they have it.¹ ET, also known as primary thrombocytosis, refers to the presence of a higher-than-normal platelet count that is not found to be caused by any other health condition.^2,3 The condition is found by chance when a routine blood test is done. 

However, not all high platelet counts mean ET⁽⁴ In fact, the majority of people with an elevated platelet count are found to have other conditions. That is why it is important for doctors to rule out other possible causes.    

Polycythemia Vera (PV): Shares a similar genetic mutation with ET that leads to primarily increasing the number of red blood cells (RBCs), but may also elevate platelet count.^5,6,7

Chronic Myeloid Leukemia (CML): Can be mistakenly diagnosed as ET due to the significant increase in platelet numbers, but it involves a different genetic mutation.^8,9

Reactive (or Secondary) Thrombocytosis (RT): Symptoms of RT are caused by another condition rather than the elevated platelet count itself.^9,10

ET is part of a group of rare blood malignancies called myeloproliferative neoplasms  (MPNs), along with PV and CML, where the bone marrow produces too many blood cells.^4,11,12

In this article, we will explore how doctors tell these conditions apart, why it matters, and what it means for patients.

What is essential thrombocythemia (ET)?

ET is a rare blood cancer, affecting about 1.5 - 2.5 out of every 100,000 people each year.^4,13

For many people with ET, the first symptoms they experience could be: 

• Thrombotic, meaning dangerous blood clots¹⁴ 
• Hemorrhagic, meaning unexpected bleeding¹⁵
• Feeling intense burning pain, particularly in the hands and feet 
• Itching or tingling when touching water

What causes ET?

ET is caused by a genetic mutation in the stem cells  of the bone marrow.¹⁶ Several can become mutated, leading to uncontrolled platelet production. The most common genetic mutations linked to ET are:⁴

• Janus Kinase (JAK2) mutation, found in 55% of people with ET
• Calriticulin (CALR) mutation, found in 15-24% 
• Myeloproliferative leukaemia (MPL) mutation, found in about 4%

Important note: Not all high platelet counts mean cancer

It could mean something serious, like ET or something harmless and temporary, like reactive thrombocytosis.¹

Polycythemia vera (PV)

PV is a rare chronic  (long-term) condition with no known cure.^5,17 Around 50 out of every 100,000 people a year in the US are affected by PV. Like ET, it is a type of cancer known as MPN.^4,6,7

In most cases, PV is caused by the same genetic mutation as ET, the JAK2 mutation.^4,5 But in some people, it can also be caused by cytogenetic mutations, which means changes or mistakes in the chromosomes.¹⁸

What makes PV different is that it primarily causes an increased production of RBCs.⁵ This increase also often comes with elevated white blood cells and platelets. Because of the extra cells, the blood becomes thicker (more viscous) than normal, raising the risk of dangerous blood clots forming. 

Clues it might be PV, not ET

Distinguishing PV from ET has proven to be difficult due to their shared genetic mutation of JAK2.¹⁹ However, healthcare professionals use specific blood tests to tell them apart. One key test measures the number of RBCs and the thickness of the plasma to distinguish each disease^19,20

It is important to get the right diagnosis as the treatments for each disease are different.¹⁹ For example, the treatment for PV is removing blood. If a patient is mistakenly diagnosed with PV, it could lead to iron deficiency anaemia.^21,19

Chronic myeloid leukaemia (CML)

CML is a type of blood cancer that starts in the bone marrow, where new blood cells are made.⁸ It affects certain early cells that would normally grow into healthy blood cells, but instead turn cancerous. The genetic mutation is found in the Philadelphia chromosome (BCR-ABL gene), and this mutation is the distinguishing feature from other blood disorders, such as PV and ET.²²

CML is also known as chronic myelogenous leukaemia or chronic granulocytic leukaemia.⁸ About 1 in every 565 people in the U.S. will develop CML at some point in their lives. And thanks to modern targeted treatments, many people with CML can now live long, full lives. What used to be a very serious and often deadly disease is now something that can usually be controlled with daily medication, like a long-term health condition.

How can CML be confused with ET?

CML and ET can both present with elevated platelet counts, which is why they can sometimes be confused, especially in the early stages.⁹ However, the underlying cause is different: ET is a chronic condition where the bone marrow produces too many platelets without a clear trigger, whereas in CML, the increase in platelets (and sometimes white cells) is due to a cancerous process driven by the BCR-ABL gene. Genetic testing for the Philadelphia chromosome is crucial for making the correct diagnosis and guiding treatment.

Reactive thrombocytosis

What is reactive thrombocytosis? 

RT, also known as secondary thrombocytosis, happens when your body makes too many platelets in response to another underlying health event, for example:¹⁰

• Smoking or alcohol consumption
• Infections²³ 
• Inflammation²⁴
• Haemorrhage
• Certain medications
• Surgery, especially to remove the spleen
• Anaemia (iron-deficiency anaemia)

RT is much more common than ET and usually causes no noticeable symptoms.¹⁰ It is often detected during routine blood tests. In extreme cases of RT, blood clots can block major blood vessels, which can lead to serious and life-threatening illnesses. Examples include:

• Acute myocardial infarction (heart attack): Occurs when blood flow to the heart is reduced or stopped²⁵
• Pulmonary embolism: Occurs when a blood clot travels to the lungs²⁶
• Mesenteric vein thrombosis: Occurs when blood flow to the intestines is blocked²⁷

How is RT different from ET:

Summary

Essential Thrombocythemia (ET) is a rare blood condition where the body makes too many platelets, often without any symptoms. It's usually discovered by accident during a routine blood test. While it may sound serious, not all high platelet counts mean someone has ET. In fact, many cases turn out to be caused by other conditions that look similar at first.

Doctors need to rule out other possible causes before confirming ET. Three main conditions often confused with ET are:

• Polycythemia Vera (PV) – a related blood cancer that mainly increases red blood cells, but can also raise platelets
• Chronic Myeloid Leukaemia (CML) – a slow-growing blood cancer that starts in the bone marrow and can cause high platelets
• Reactive Thrombocytosis (RT) – a temporary spike in platelets caused by things like infections, inflammation, or bleeding, and not by cancer

All of these conditions can lead to high platelet levels, but the causes and treatments are very different. ET is usually caused by genetic mutations in the bone marrow (like JAK2, CALR, or MPL). PV is often also linked to JAK2, while CML is caused by a different genetic change. RT, on the other hand, is not a cancer — it's a reaction to another health problem and usually goes away once that issue is treated.

Getting the right diagnosis is essential because the wrong treatment can lead to complications. For example, PV is sometimes treated by removing blood, which could cause iron deficiency if the patient actually has ET or RT.

Although ET is a chronic condition and considered a type of blood cancer, many people with it can live long, healthy lives with the right treatment and monitoring.

FAQ’s 

What should I do if I am told I have high platelets? 

Your doctor may order more follow-up blood tests a few weeks after to check if the levels have stayed high. If your levels have returned to normal, then there is usually nothing to be concerned about, but if they remain high, they may run some more tests. Such as:³⁰

More blood tests: to check for signs of inflammation, abnormal platelets, or conditions that may cause high platelets

Genetic tests: to check genes associated with ET:

• MPL
• JAK2
• CALR

Bone marrow biopsy: to check for abnormal platelets, which may confirm ET³¹

What is the normal number of platelets? 

Between 150,000 and 400,000 platelets per microliter³⁰

Is a high platelet count always dangerous?

Not all high platelet counts mean cancer. It could mean something serious, like ET or something harmless and temporary, like reactive thrombocytosis.¹⁰ Additionally, heavy drinking, recovery from serious blood loss and having low levels of B12 or folate may temporarily cause high platelet levels.¹

What is essential thrombocythemia? 

ET is caused by a genetic mutation. Several stem cells can become mutated, leading to uncontrolled platelet production.⁴

What other conditions can cause high platelets? 

The list of possible conditions that can look like essential thrombocythemia (ET) is wide and includes other types of blood cancers, as well as temporary or false increases in platelet counts due to other causes.²⁹
Such as: 

• Polycythemia Vera²⁹
• Chronic myeloid leukemia⁹
• Reactive (or secondary) thrombocytosis²⁹