Diagnosis

While certain signs and symptoms may indicate that a person has PV, 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

Medical History and Physical Examination

Evaluation of an individual with suspected PV should start with a detailed medical history and a physical examination.

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

  • Cardiovascular risk factors
  • Past illnesses and injuries 
  • Current and past medications and treatments
  • History of thrombus (blood clot) or a hemorrhagic event (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 (CBC) with Differential: This test measures the number of red blood cells, white blood cells and platelets in a sample of blood. It also measures the amount of the iron-rich protein that carries oxygen in red blood cells and the percent of whole blood made up of red blood cells (the hematocrit). People with PV have high red blood cell counts. They also often have:
    • Increased hemoglobin levels
    • Increased hematocrit levels
    • Increased white blood cells and platelets
  • Red Cell Mast Test: This procedure is used to measure the volume (amount) of red blood cells in relation to the volume of plasma (fluid) in whole blood. In patients with PV, there may be an absolute increase in red blood cell mass. This test is infrequently performed in the United States due to high cost, difficulty obtaining the appropriate test materials, and the advent of new blood tests such as molecular testing.
  • 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 PV, 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.
  • Erythropoietin (EPO) Level. This test measures the level of erythropoietin (EPO) in the blood. EPO is a hormone primarily made in the kidneys to stimulate the production of new red blood cells. In people with PV, high red blood cell counts can suppress EPO levels. Results of EPO tests can be used to help diagnose PV.

Bone Marrow Tests

Your doctor may examine your bone marrow even though the test isn't needed to diagnose PV.

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

In PV, the bone marrow shows above-normal numbers of blood cells and an abnormal number of the platelet-forming cells called “megakaryocytes” in the bone marrow. The pathologist also examines the chromosomes of the bone marrow cells to rule out other blood diseases. 

Molecular Tests

These tests 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.

Polymerase chain reaction (PCR): This is a very sensitive test used to detect and measure specific genetic mutations that are too small to be seen with a microscope. PCR testing basically amplifies (increases) small amounts of specific pieces of DNA so that they are easier to detect and measure in a cell sample. It looks for the presence or absence of specific gene mutations. PCR testing can be done with blood or bone marrow samples.

DNA sequencing: DNA sequencing refers to a number of different laboratory tests that examine the exact sequence (order) of DNA. By comparing the sequence of DNA in cancer cells with the DNA in normal cells, doctors can find genetic changes that are unique to the cancer cells and may be driving the growth of the patient’s cancer. DNA sequencing can be done with blood or bone marrow samples.

If PV is suspected, testing for the JAK2 gene mutation should be performed. The JAK2 V617F mutation is found in more than 95 percent of PV patients. If a patient does not have a JAK2 V617F mutation, then testing should be done for other mutations. About 2-3 percent of PV patients have the JAK2 exon 12 mutation.

For more information about bone marrow tests and other lab tests, please see the free LLS publication Understanding Lab and Imaging Tests.
 

Criteria for Diagnosing Polycythemia Vera

In 2016, the World Health Organization published new criteria for diagnosing PV.

Diagnosis requires 3 major criteria OR 2 major criteria + 1 minor criterion.

Major Criteria 1.  Very high red blood cell count, usually identified by either A, B, or C below:

  • A. Elevated hemoglobin level
    • Hemoglobin levels greater than 16.5 g/dL in men
    • Hemoglobin levels greater than 16.0 g/dL in women
  • B. Elevated hematocrit level
    • Hematocrit greater than 49 percent in men
    • Hematocrit greater than 48 percent in women
  • C. Increased red cell mass

Major Criteria 2. Bone marrow biopsy showing abnormally high numbers of blood cells in the bone marrow (called “hypercellularity”) based on the person’s age. This includes elevated red blood cell, white blood cell and platelet counts (a condition called “panmyelosis”) and proliferation of mature megakaryocytes (platelet-forming cells) that vary in size and shape

Major Criteria 3. Presence of the JAK2V617F or JAK2 exon 12 gene mutation

Minor Criterion: Very low erythropoietin level

 

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