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Symptoms, Diagnosis, & Risk Factors

MPN Symptoms

Some people with myeloproliferative neoplasms (MPN) have no symptoms when their disease is diagnosed. But a routine blood test may show high levels of red blood cells, white blood cells, or platelets. Other people with MPN may have general symptoms, such as fever, night sweats, and weight loss. Each type of MPN may cause specific symptoms related to high blood counts.

Polycythemia Vera (PV) Symptoms

Symptoms of PV, in which there are too many RBCs, may include the following:

  • A feeling of pressure or fullness below the ribs on the left side
  • Headaches
  • Double vision or seeing dark or blind spots that come and go
  • Itching all over the body, especially after being in warm or hot water
  • Reddened face that looks like a blush or sunburn
  • Weakness
  • Dizziness
  • Weight loss for no known reason

Essential Thrombocythemia (ET) Symptoms

Symptoms of ET, in which there are too many platelets, may include the following:

  • Headaches
  • Stroke symptoms
  • Chest pains
  • In some cases, bleeding

Primary Myelofibrosis (PMF) Symptoms

Symptoms of PMF, in which fibers and blasts (abnormal stem cells) build up in the bone marrow, may include the following:

  • Weakness and fatigue from severe anemia
  • Abdominal pain and fullness from enlarged spleen and liver

Complications

A major complication of MPN is blood clots in the arteries, causing heart attacks and strokes, or in the veins, causing deep vein thrombosis and pulmonary emboli (clots that block the arteries that go from the heart to the lungs). Budd Chiari syndrome is a severe type of clot that involves the blood vessels leading to the liver. Blood clots can occur early, even before the diagnosis, and late in the disease.

Other complications may include the following:

  • Scarring of the bone marrow, called myelofibrosis. In PMF, this scarring can occur early on and be the main finding in the disease. In PV and ET, scarring can occur after many years of disease.
  • The transformation of MPN into acute leukemia.

Diagnosis

To find out whether you have MPN, your doctor will first do a thorough physical exam and ask about your health history and any symptoms.

Next your doctor will perform a series of blood tests to tell whether any blood cells are abnormal and, if so, which ones. Common blood tests include the following:

  • Complete blood count (CBC): determines how many cells of each type are circulating in the bloodstream
  • Peripheral blood smear: looks at the appearance of the blood cells
  • Blood chemistry: looks for abnormalities in the blood, including certain enzymes or abnormal iron level

Bone Marrow Aspiration and Biopsy

For a definitive diagnosis, doctors generally need to perform a bone marrow aspiration and biopsy. A small area of skin over your lower back (pelvis) is cleaned and numbed. Then a marrow needle is used to withdraw bone marrow. If a biopsy is performed, the doctor uses a different needle to remove a small piece of marrow from your bone (a marrow core). In either case, the sample will be examined under a microscope to determine the presence and number of abnormal cells in your marrow and whether you have myelofibrosis.

Cytogenetic Analysis

In addition, doctors will perform cytogenetic analysis. This means your marrow cells will be set up in a culture dish to make them divide. This will allow us to see your chromosomes under a microscope and tell whether any are abnormal. Doctors use the number and type of chromosome abnormalities to help predict how your disease will progress and which types of treatment might be most effective. Your chromosomes contain your genes and can provide instructions for how your cells function.

Fluorescent in situ hybridization (FISH) is a specialized cytogenetic analysis. The fluorescent dyes used in this test attach to specific parts of certain chromosomes. More chromosomal abnormalities can be seen under a microscope using this technique than with the standard technique described above.

Molecular studies are very sensitive, specific tests for gene mutations associated with different myeloproliferative processes. Your doctors will use these tests to look for one or more of the following mutations:

  • BCR-ABL: a genetic joining of two genes found almost exclusively in chronic myeloid leukemia and rare cases of acute lymphoid leukemia
  • JAK2 V617F: a small mutation found in more than 90 percent of cases of PV and approximately 50 percent of cases of ET and PMF
  • MPL mutations: mutations in a protein that is found in some cases of ET
  • C-KIT D816V: a small mutation found in most cases of mastocytosis
  • FIP1L1-PDGFR: a genetic joining of two genes found in some cases of hypereosinophilia and associated with how the disease responds to treatment

Other Tests

You may have flow cytometry (a computer analysis of cells) to tell how your disease is progressing.

Risk Factors

Doctors don’t know what causes the cellular changes that lead to MPN. Exposure to toxins, such as benzene, certain solvents or pesticides, and heavy metals, such as mercury or lead, may be involved in the development of genetic changes in stem cells. It is extremely difficult, if not impossible, to establish a clear cause-and-effect relationship between those exposures and the development of MPN.

MPN is seen in all age groups but is more common in middle age and older adults. PV is more common in men, and ET and PMF are more common in females. Very rarely, there can be clustering of cases in families that have an inherited genetic defect.

References
Leukemia & Lymphoma Society
MPN Research Foundation
National Cancer Institute

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