Polycythemia Vera

What is polycythemia vera?

Polycythemia vera (PV) is a blood disorder that causes your body to produce too many red blood cells. Too many red blood cells can make your blood thick and sluggish and increase your risk of blood clots and complications such as heart attack and stroke. It can also cause vague but irritating symptoms, such as skin itchiness, ringing in your ears, abdominal pain, nose bleeds and blurred or double vision.

Polycythemia vera is a chronic condition with no cure, but medical care can help you manage symptoms and the risk of complications. Other names for polycythemia vera include primary polycythemia, polycythemia rubra vera, erythema and Osler-Vaquez disease.

Is polycythemia vera cancer?

Polycythemia vera is a type of blood cancer known as myeloproliferative neoplasm (MPN). MPNs are a group of various diseases, some of which cause overproduction of different blood cells. A gene mutation that occurs for unknown reasons, usually sometime during the course of your life, causes polycythemia vera. They develop very slowly and often aren’t diagnosed until after the age of 60. This type of cancer usually isn’t fatal by itself. The risk comes from complications of blood clotting, or from the small chance that it would progress more aggressive types of blood cancer.

Who does polycythemia vera affect?

Polycythemia vera is rare. It affects about 50 per 100,000 people in the U.S. It’s most common in people over the age of 60.

How does this condition affect my body?

Polycythemia vera causes your body to produce too many red blood cells. Extra blood cells increase your likelihood of bleeding, bruising and clotting. They thicken your blood and slow your circulation, which means your blood carries less oxygen to your body’s tissues and organs than they need. They also overwork your spleen, which is responsible for filtering your blood and clearing out old blood cells. This can lead it to become swollen and sore (splenomegaly). Over time, you may develop a variety of uncomfortable symptoms as a result of your condition. PV can also lead to several secondary conditions.

What are the risks and complications of polycythemia vera?

PV progresses slowly, but overproduction of blood cells carries immediate risks from blood clots. Over time, polycythemia vera may also induce secondary conditions. It rarely progresses to a more serious kind of cancer.

Blood clots

The most urgent risk from polycythemia vera is the tendency for blood clotting. A blood clot that travels to your heart or brain can cause a heart attack or stroke. A clot that gets stuck in your lungs (pulmonary embolism) can cause pulmonary hypertension, leading to heart failure. A blood clot that blocks a vein (venous thromboembolism) can cause tissue death and chronic venous insufficiency. A clot that blocks the main blood vessel leading to your liver (hepatic vein thrombosis) can cause blood to back up into it (Budd-Chiari syndrome), leading to jaundice and liver failure.

Secondary conditions

High red blood cell turnover also produces high uric acid levels in your body. This contributes to several secondary conditions, including kidney stones (when uric acid builds up in your kidneys) and gout, a painful form of arthritis (when uric acid builds up in your joints). Extra red blood cells also lead to more stomach acid, which can cause stomach ulcers. The extra red blood cells trigger an immune response in your body. Your body releases a chemical called histamine, and your stomach responds by creating more acid to fight off infection. People with PV are four times as likely as others to have peptic ulcer disease.

Leukemia progression

Polycythemia vera is a form of chronic bone marrow disorder/cancer, which usually isn’t an urgent threat. With regular treatment, it can be managed well for many years. But in some people, PV does progress to other more aggressive blood disorders, including, but rarely, acute leukemia.

Stages of polycythemia vera progression

• Early PV: This phase often has no symptoms or only mild symptoms.
• Advancing PV: As polycythemia vera advances, you may begin noticing more uncomfortable symptoms or the development of secondary conditions.
• Spent phase: The so-called “spent phase” of PV occurs when the mutated blood cells that caused the condition have grown so out of control that they’ve taken over your bone marrow, where blood cells grow. As the mutated cells lived out their lives and broke down, they were replaced with scar tissue. When enough of your bone marrow has been replaced with scar tissue, it’ll no longer be able to produce healthy blood cells. Ironically, this leads to anemia — a lack of healthy red blood cells. It also increases your risk of hemorrhage from bleeding.

Post-polycythemia vera blood disorders

• Myelofibrosis: The “spent phase” of polycythemia vera is basically identical to another type of blood cancer called myelofibrosis (MF). Some healthcare providers make no distinction between the two. Myelofibrosis occurs when mutated cells have replaced your bone marrow with scar tissue. The abnormal cells may also begin to spread outside of your bone marrow to other organs in your body. MF is another myeloproliferative disorder. About 10% of MF cases may progress to acute myeloid leukemia.
• Myelodysplastic syndrome: More rarely, PV may turn into a myelodysplastic syndrome (MDS), a kind of disorder in which blood cells don’t fully develop. Whereas PV normally produces an abundance of red blood cells that mature normally, MDS causes blood cells to mature abnormally/improperly, and die early. The inability to form healthy and mature cells causes a lowering of various blood counts (can be one type of low counts or a combination). MDS can occur instead of or simultaneously with myelofibrosis. It’s more aggressive than PV or MF and has a 30% chance of progressing to acute myeloid leukemia (AML).
• Acute myeloid leukemia (AML): About 3% of polycythemia vera cases may progress to acute myeloid leukemia over the course of about 10 years from diagnosis. AML is an aggressive blood cancer that begins in your bone marrow and quickly moves into your bloodstream, where it can spread to other body systems. AML requires more urgent treatment than chronic leukemia, but it has a high survival rate. It accounts for less than 2% of all cancer deaths.

What are the symptoms of polycythemia vera?

Symptoms usually develop slowly over time, if they appear at all. They often begin with the kind of vague complaints that are common to many disorders, including:

• Headaches.
• Dizziness.
• Fatigue.
• High blood pressure.
• Blurred or double vision.
• Tinnitus (ringing in your ears).

Eventually, some more curious symptoms may develop, including:

• Excessive sweating, especially at night.
• Shortness of breath, especially when lying down.
• Itchy skin, especially after a warm bath or shower.
• Redness, heat, tingling or burning in your hands and feet.
• Excessive bleeding or bruising. Nosebleeds and gum bleeding.
• Unexplained weight loss.

If PV progresses to a secondary condition, you may experience symptoms of that condition. For example:

Symptoms of splenomegaly (enlarged spleen)

• A dull ache on the upper left side of your abdomen.
• A bloated feeling in your abdomen.
• Feeling full after eating only a small amount.

Symptoms of peptic ulcer disease

• Gnawing stomach pain.
• Heartburn.
• Acid reflux.

Symptoms of gout

• Painful inflammation in your joints.
• Stiffness.
• Swollen big toe.

Symptoms of kidney stones

• Pain in your lower back or side.
• Painful urination.
• Frequent urination.

Symptoms of Budd-Chiari syndrome

• Enlarged liver causing bloating and pain in your upper right abdomen.
• Jaundice causing yellowing of your eyes and skin.
• Ascites causing abdominal swelling and edema.

Symptoms of deep vein thrombosis (DVT)

• Swelling and tenderness in an arm or leg.
• Redness or heat at the site.
• Enlarged veins on the surface of your skin.

Symptoms of pulmonary embolism (PE)

• Sudden chest pain.
• Breathlessness.
• Rapid heart rate.

Symptoms of anemia

• Light-headedness.
• Paleness.
• Fatigue.

What causes polycythemia vera?

Polycythemia vera occurs in your bone marrow, the soft, spongy material at the center of your bones. This is where new blood cells grow. PV begins when a single gene within a single stem cell in the bone marrow malfunctions. More than 90% of the time, it’s a gene called JAK2. The mutated gene gives instructions to the stem cell to continually reproduce itself. All of the reproduced cells also continue to reproduce, until the abnormal cells crowd out the normal cells in your bone marrow. Most of the time, the JAK2 gene mutation is acquired, which means it isn’t inherited from a family member. It occurs for unknown reasons sometime during your life. But there have been a few documented cases of multiple family members developing polycythemia vera.

How is polycythemia vera diagnosed?

The World Health Organization (WHO) requires three separate criteria to diagnose polycythemia vera:

Criteria 1: Blood test showing high red blood cell count:

Red blood cells may be measured as:

• High hemoglobin count (protein found in red blood cells).
• High hematocrit levels (percentage of red blood cells).
• High blood volume (red cell mass).

Criteria 2: Bone marrow biopsy showing either:

• Excess of blood cells in the bone marrow, or
• Excess of mature megakaryocytes (the cells that make blood platelets).

Criteria 3: The third criteria can be met by showing either:

• Molecular testing showing the presence of the JAK2 gene mutation, or
• Blood test showing very low levels of erythropoietin (a hormone produced by your kidneys to stimulate red blood cell production).

How is polycythemia vera treated?

In the early stages, PV is treated conservatively. Typical treatments include:

Phlebotomy

The most common treatment for PV is to have regular blood withdrawals. It’s the same procedure you would have to donate blood. A healthcare technician inserts a needle into a vein in your arm and withdraws a small amount of blood — usually a pint, but it may vary depending on your condition. This reduces your overall blood volume and your number of excess blood cells.

Low-dose aspirin

This over-the-counter medication is commonly prescribed to reduce the risk of blood clotting. A low daily dose of aspirin helps prevent blood platelets from sticking together. It can also help reduce symptoms of inflammation in your hands and feet. However, it’s hard on the stomach and increases your tendency to bleed, so it may not be a good idea if you have stomach ulcers.

If your symptoms have become more severe, or if you have a history of thrombosis (blood clotting) and are considered higher risk, you may be offered additional treatment options. Some of these include:

Treatments to reduce itching

Your healthcare provider may prescribe medications to treat the itching symptoms of advanced PV, including:

• Antihistamines: These are over-the-counter allergy medications.
• Phototherapy: Treatment combines ultraviolet (UVA) light with a medication called psoralen, an organic compound that makes your skin more receptive to phototherapy.
• Selective serotonin reuptake inhibitors (SSRIs): These medications are normally used to treat depression, but in much lower doses, they have shown to be effective against persistent physical irritation, such as itching.

Drugs that reduce red blood cell count

These may be used individually or in combination with each other. Examples include:

• Hydroxyurea.
• Interferon alfa.
• Ruxolitinib.
• Busulfan.

Clinical trials

Clinical trials offer people the chance to try new emerging treatments while contributing to medical research. Some of the medications being researched include:

• Peginterferon alfa-2a.
• Givinostat.
• Idasanutlin.

Bone marrow transplant

A bone marrow transplant may be recommended in some cases. Your healthcare provider will consider several different factors, including the severity of your condition and your body’s healing capacity.

Supportive care

If PV continues to progress despite treatment, your healthcare provider will focus on relieving your symptoms. Late-stage PV is often characterized by anemia and an increasingly enlarged spleen. You may be treated with:

• Pain relief.
• Blood transfusions.
• Low-dose radiation to your spleen.

What is the life expectancy for someone with polycythemia vera?

Recent studies estimate the average life expectancy after diagnosis with polycythemia vera to be about 20 years. The average age of death is about 77. The most common cause of death is complications from blood clots (about 33%). Advancing cancer is the second most common cause (15%).

How can I take care of myself and manage my symptoms?

If you’re living with polycythemia vera, it’s important to keep in touch with your healthcare provider so they can keep track of how your condition is progressing. Let them know how you’re responding to treatment and if you’re experiencing any side effects. You may continue living a long time without severe symptoms.

In addition to regular testing and treatment, your healthcare provider will likely recommend general lifestyle changes to help prevent blood clots and other complications. For example:

• Exercise. Even moderate exercise can help improve sluggish circulation.
• Avoid smoking. Smoking causes your blood vessels to narrow.
• Avoid low-oxygen environments. High altitudes can reduce oxygen levels in your blood.
• Keep your blood pressure in check. Maintaining a healthy body weight can help with this.

A note from Cleveland Clinic

Polycythemia vera (PV) is a kind of cancer, but most people continue living well for decades after diagnosis. It qualifies as a cancer because it involves uncontrolled cell production. However, it takes a long time for uncontrolled production of red blood cells to begin affecting you. And when they do, you can manage your condition for a long time by simply having some of your extra blood drawn.

The most significant threat from polycythemia vera isn’t from cancer itself, but from the risk of blood clots. If you’re living with PV, make sure to see your healthcare provider regularly. And don’t neglect taking care of yourself in the “little ways” — healthy lifestyle habits that can help maintain your general cardiovascular health, which might turn out to be just as important as any medical treatment for polycythemia vera.