Polycythemia Vera (PV)

What is PV?
Symptoms
Diagnosis
Progression
Prognosis/Life Expectancy
Available Treatments
Possible Causes
Prevalence

What is PV?

Polycythemia Vera (PV) is a chronic progressive myeloproliferative neoplasm (MPN) primarily characterized by an elevation of the red blood cells. Patients may also have an elevated leukocyte (white blood cell) count, an elevated platelet count, and an enlarged spleen.

In 2005, it was discovered that 95% of patients with PV have a mutation in the JAK2 gene. This gene plays a significant role in the production of red blood cells (in addition to white blood cells and platelets). When the gene is mutated (JAK2 V617F), there is a loss of normal regulation, and an overproduction of red blood cells, and at times, white blood cells and platelets. The discovery of this mutation propelled a broad range of scientific projects which will hopefully result in new and effective treatments for PV and the other myeloproliferative neoplasms.

Symptoms

PV patients may present with a variety of symptoms, or may be relatively asymptomatic, discovered incidentally during a routine doctor’s visit. Symptoms can include:

• Headache
• Sweating
• Ringing in the ears
• Blurred vision or blind spots
• Dizziness or vertigo
• Reddish or purplish skin
• Unexpected weight loss
• Bleeding or clotting
• Early feeling of fullness (satiety)
• Itching (pruritis), especially after the shower
• Burning and redness of the hands or feet
• Tiredness (fatigue)
• Night sweats
• Bone pain

Diagnosis

In many cases, the diagnosis is incidental, often after a routine complete blood count which reveals in increase in the red blood cells, along with an increase in the white blood cells and/or platelets. In other cases, doctors may recognize signs of the disease on an examination, including a redness to the complexion, or an increase in the size of the spleen.

Common diagnostic tests include:

• Complete blood count, revealing in increase in the hemoglobin (along with the white blood cells and/or platelets

• JAK2 V617F mutation (positive in 95% of patients)

• Low erythropoietin level (a hormone involved in red blood cell production—it is low because blood cell production is being driven by another stimulus in JAK2 V617F)

• Bone marrow biopsy, revealing an excess in the proliferation of precursors to red blood platelets, red blood cells, and white blood cells

Progression

PV differs from many other hematological malignancies in that prolonged survival is enjoyed by most patients, but the clinical course can be compromised by symptoms such as fatigue and post-bath itching, or blood clotting complications, either in the arteries (stroke, “mini-stroke,” or heart attack), or veins (deep vein thrombosis, pulmonary embolus, and blood clots in abdominal veins).

Prolonged survival can be interrupted by development of other syndromes including, in approximately 15% of cases, myelofibrosis (a progressive bone marrow disorder that results in bone marrow scarring, severe anemia, and enlargement of your liver and spleen); this change can be heralded by the onset of anemia, or a low red blood count, as opposed to high red blood counts, and a significant increase in the size of the spleen). In a smaller number of cases, PV may progress to acute leukemia (AML).

Prognosis/Life Expectancy

Polycythemia vera patients have an excellent chance of living out a normal life span if properly monitored and treated as necessary. The most common cause of morbidity and mortality is the predisposition of PV patients to develop life threatening arterial thromboses (heart attacks, strokes, intestinal gangrene), venous thromboses (of the portal and/or hepatic veins), or pulmonary embolism. Important strategies for care can include aspirin, and control of the blood counts in those at high risk. For others, life expectancy can be compromised as the disease evolves to myelofibrosis, or rarely, acute leukemia.

Available Treatments

Your doctor can describe available treatments that may be appropriate for you. Polycythemia Vera (PV) is different in every person. If you don't have a lot of symptoms, your doctor may decide that you don't need treatment yet. Instead, your doctor will observe and monitor your condition.
 
Treatment to return hematocrit to normal values is the cornerstone of management. Treatment options include:

• Phlebotomy—Removal of blood; some people may require this procedure as their disease develops. It reduces the number of blood cells. With fewer blood cells, the blood is thinner and flows more easily. Better blood flow improves symptoms. At present, your physician targets your blood count goals depending on sex (45% or less in men, and 42% or less in women is often recommended), though researchers are evaluating the optimal target in the future.

• Low-dose aspirin—many, if not all, people will get this treatment. Aspirin prevents platelets from sticking together. This helps prevent blood clots that can cause life-threatening heart attacks or strokes.

Maintaining a hematocrit below .45 and .42 for men and women respectively, along with low dose aspirin, is currently accepted as a nonleukomegenic approach and first choice treatment in newly-diagnosed low risk PV patients.

If phlebotomy and low-dose aspirin are not sufficient or appropriate, your doctor may prescribe medicine to lower your red blood count and relieve symptoms. Currently there are no drugs approved by the Food and Drug Administration (FDA) to specifically treat Polycythemia Vera. However, some medicines approved for other diseases are used to treat the signs and symptoms of this condition (see PATIENT OPTIONS/Drug Reimbursement). A physician will prescribe one of these options based on a variety of risk factors including age (over 60), history of thrombotic events, and drug tolerance, or if certain disease related symptoms cannot otherwise be controlled. Current options include:

• Hydroxyurea--Often considered in those at high risk for blood clots, based on age and prior history of blood clotting.

• Pegylated interferon--Younger patients who need treatment, and women of childbearing age are often treated with this agent because it hasn't been shown to cause birth defects

In the next several years, it is anticipated that new drugs based on the discovery of the JAK2 gene and other scientific research will be approved to treat PV. Some of these drugs are currently in clinical trials. Please see our MPN Research News section for breaking news on these new treatments.

Possible Causes

No one knows exactly what triggers the start of Polycythemia Vera (PV) or other myeloproliferative neoplasms (MPNs). Recently, researchers discovered that these diseases may be caused by mutations (changes in DNA). These mutations affect proteins that work in signaling pathways in your cells, which can be thought of as a chain of signals that your cells use to communicate messages and know what to do.

Almost all people with Polycythemia Vera have a mutation called “JAK2V617F” (found in the JAK2 gene) within their blood-forming cells. This mutation is one way that JAK (Janus kinase) pathway signaling can become dysregulated and cause disease. The end result is that the body makes too many blood cells.

Researchers now know that Polycythemia Vera is complex and may have many contributing factors, and mutations in other genes or pathways are being investigated.

Epidemiologic factors associated with PV may also include:

• Gender -- Men may be slightly more likely than women to develop the condition.
• Age -- People older than 60 are most likely to develop the condition, though it may occur at any age.
• Environment – Exposure to intense radiation may increase the risk for the condition.

There is anecdotal evidence that PV may sometimes be caused by exposure to toxic substances, but there have not been definitive studies in this area. Recently a cluster of PV cases were identified in three counties in Pennsylvania adjacent to a Superfund Cleanup site, and this cluster is being studied using funds allocated by the U.S. federal budget. Click here for more information on the results of these studies to date.

Prevalence

A common question often has to do with the prevalence and incidence of MPN; these terms refer to the total number of patients currently living with disease and the number of newly diagnosed patients each year, respectively.

To investigate this further and try to put an end to speculation, the MPN Research Foundation co-sponsored with the Leukemia and Lymphoma Society a grant to assess the prevalence of MPNs. Dr. Xiaomei Ma of Yale University School of Medicine was the lead investigator on the study on prevalence of MPDs that was published in the American Journal of Hematology (1). The study looked exclusively at the prevalence of the MPNs PV and ET, excluding Myelofibrosis.

According to this study on the prevalence of MPNs, there are 22 cases of PV and 24 cases of ET per 100,000. The study says there is an estimated total of 65,243 patients with PV and 71,078 with ET in the United States in 2003, for a total of approximately 136,000 patients. This number may be increased as the discovery of the JAK2 mutation has facilitated the diagnostic work-up. Another study has evaluated national databases to determine the number of new cases per year (Rollison Blood 2008)

1. Ma X, Vanasse G, Cartmel B, Wang Y, Selinger HA. Prevalence of polycythemia vera and essential thrombocythemia.
2. Mesa R, Silverstein M, Jacobson, Wollan P, Tefferi A. Population-based incidence and survival figures in essential thrombocythemia and agnogenic myeloid metaplasia: an Olmsted county study, 1976-1995.