Diagnosis

While certain signs and symptoms may indicate that a person has ET, a series of tests are needed to confirm the diagnosis. It is important to have an accurate diagnosis, as it helps the doctor to: 

  • Estimate how the disease will progress
  • Determine the appropriate treatment

Some of these tests may be repeated both during and after treatment to evaluate its effectiveness.

Medical History and Physical Examination

Evaluation of an individual with suspected ET should start with a detailed medical history and a physical examination by a hematologist-oncologist

The medical history should include information about the patient’s:

  • Cardiovascular risk factors, such as high blood pressure and diabetes 
  • Past illnesses and injuries 
  • Current and past medical treatments
  • History of thrombus (blood clot) or hemorrhagic events (loss of blood from damaged blood vessels) 
  • Family medical history 
  • Current symptoms 

After the medical history, the doctor will conduct a physical examination. During the physical examination, the doctor may:

  • Listen to the patient's heart and lungs
  • Examine the patient's body for signs of disease
  • Check different organs of the body

Blood Tests

  • Complete Blood Count with Differential: This test measures the number red blood cells, white blood cells and platelets in a sample of blood. It also measures the amount of substance in the blood that carries oxygen (hemoglobin) and the percent of whole blood that is made up of red blood cells (hematocrit). In patients with ET, the platelet count is higher than normal.
  • Peripheral Blood Smear: A pathologist examines a small amount of blood under a microscope to see if there are any unusual changes in the size, shape, or appearance of the blood cells. The test also looks for the presence of immature (blast cells). In patients with ET, the platelets may appear enlarged and/or clumped together.
  • Blood Chemistry Profile: This blood test measures the levels of certain substances released into the blood by organs and tissues in the body. These substances include electrolytes (such as sodium, potassium and chloride), fats, proteins, glucose (blood sugar), uric acid and enzymes. The test findings indicate how well a person’s kidneys, liver and other organs are working. Although this test is not used to diagnose ET, if the results show that there is an abnormal amount of a particular substance in the blood, it may be a sign of disease or some other health problem.
  • Blood Clotting Tests: Patients with very high platelet counts may be tested for acquired von Willebrand disease, a blood disorder that can impair normal blood clotting and cause major bleeding. Blood contains many proteins that help the body stop bleeding, one of which is known as von Willebrand factor. High platelet counts can limit how well the von Willebrand proteins clot. Several blood clotting tests are used to diagnose von Willebrand disease

Bone Marrow Tests

Although a bone marrow examination isn't strictly necessary to make a diagnosis, doctors often use it to help confirm a ET diagnosis. 

Bone marrow testing involves two steps usually performed at the same time in a doctor's office or a hospital:

  • A bone marrow aspiration to remove a liquid marrow sample
  • A bone marrow biopsy to remove a small amount of bone filled with marrow

If you have ET, your marrow will show a significant increase in platelet-forming cells (megakaryocytes). These cells also appear abnormal in shape and size.

Molecular Testing

These tests, such as polymerase chain reaction (PCR) and DNA sequencing, look for abnormal changes in the genes, chromosomes, proteins or other molecules within the patient’s cancer cells. They are used for diagnosis and treatment planning.In suspected cases of ET, doctors test for mutations of the JAK2, MPL and CALR genes.

Approximately 90 percent of patients with ET have a mutation of the JAK2, MPL or CALR gene. The approximate frequencies of these mutations are:

  • JAK2 mutation — 60%
  • CALR mutation — 20%-35%
  • MPL mutation — 1%-4%

About 10 percent of ET patients do not have a JAK2, MPL or CALR gene mutation. In these cases, the disease is referred to as “triple-negative” ET. Further study is needed to identify other mutations that may cause the disease in these patients.
 

Criteria for Diagnosis

In 2016, the World Health Organization published new criteria for diagnosing ET. Diagnosis requires 4 major criteria OR major criteria 1-3 + minor criterion.

Major Criteria

  1. Platelet count equal or greater than 450 x 109/L
  2. Bone marrow biopsy showing increased numbers of platelet-forming cells (megakaryocytes) with abnormal nuclei
  3. Exclusion of other diseases defined by World Health Organization criteria, such as:
    • BCR-ABL1+ chronic myeloid leukemia 
    • Polycythemia vera 
    • Primary myelofibrosis 
    • Myelodysplastic syndromes 
    • Other myeloid neoplasms
  4. Presence of JAK2, CALR, or MPL mutation

Minor Criterion

  • Presence of a clonal marker (chromosome abnormality) or no evidence that the disorder is caused by reactive thrombocytosis 

 

 

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