Polycythemia vera

Polycythemia vera is frequently caused by mutations (changes) affecting the JAK2 gene, and less frequently by mutations affecting the TET2 gene. JAK2 is known to provide the body with instructions to produce blood cells. When there is a mutation in this gene, the gene is constantly turned on, and the body therefore produces too many red blood cells. Having too many red blood cells cause the blood to be thicker than normal so it cannot travel as efficiently through the bloodstream. This causes an increased risk for blood clots, and it can cause the skin to be reddened. It also can mean that the organs of the body are not getting enough oxygen due to reduced blood flow, so the organs such as the spleen may swell resulting in splenomegaly.

Polycythemia vera is diagnosed by testing the blood for levels of a hormone called erythropoietin as well as testing the blood for mutations in JAK2 _or TET2_.

Erythropoietin is a hormone that is released by the kidneys and helps control the creation of red blood cells. When the body senses that red blood cell levels are too high, as they are in people who have PV, the body secretes less erythropoietin in an effort to reduce the number of red blood cells. However, because people with PV have mutations that cause red blood cells to be created constantly, lower levels of erythropoietin do not control the number of red blood cells. Because people with PV have consistently high number of red blood cells, the body tries to control this problem by secreting low levels of erythropoietin.

If low levels of erythropoietin are found in the blood as well as mutations in either JAK2 or TET2 , an individual can be diagnosed with polycythemia vera. If mutations are not found in the red blood cells but the doctors still suspect a diagnosis of polycythemia vera, a bone marrow biopsy may be done to look for mutations in the hematopoietic blood cells which are located in the bone marrow.

Even though most people with polycythemia vera (PV) have mutations in JAK2 or TET2 , that does not mean that the condition is inherited from the parents. Instead, most cases of polycythemia vera are associated with genetic changes (mutations) that are somatic. This means that the mutations occur in the cells that produce red blood cells (hematopoietic stem cell), but generally not in the egg and sperm cells which pass on genetic information to offspring.

In rare cases, the mutation to a gene that causes PV does occur in the egg or sperm cells, which increases the risk that a person with PV will pass the mutation on to their children. In these cases, the condition appears to have an autosomal dominant pattern of inheritance. This means that only one altered copy of a gene is enough to give a person an increased risk for PV. However, not every person who has a mutation in JAK2 or TET2 will necessarily develop PV. Rather, if a person has a mutation in one of these genes, he or she has an increased risk to develop PV during his or her lifetime.

The long-term outlook for individuals affected by polycythemia vera may depend on the response to treatment. The most dangerous symptom of polycythemia vera is the chance for a thrombotic event that can cause a heart attack or stroke. There is also a small chance that polycythemia vera could cause an individual to develop leukemia. With proper treatment, however, these symptoms have not been shown to greatly affect the expected lifespan of a person with polycythemia vera.

Another complication that can affect the long-term outlook for a person with polycythemia vera is the uncomfortable itching (pruritus) that can occur as part of the condition. However, many people are able to control the itching with the use of the medications listed above.

The goal of treatment for polycythemia vera is to decrease the risk for developing deep vein thrombosis. This risk is about 20% for individuals who are above 60 years old or have a history of deep vein thrombosis. The risk can be reduced by keeping the hematocrit, which is the ratio of red blood cells to the amount of total blood, below 45%. In order to decrease the number of blood cells, doctors may recommend phlebotomy, which is the process of removing blood from the veins. A person with polycythemia vera may also be told to take low-dose aspirin daily, which has been shown to help reduce blood thickening. If these treatments do not work to reduce the number of red blood cells, a therapy called hydroxyurea may be used to reduce the number of blood cells in the bone marrow. In some cases, a bone marrow transplant may be necessary to reduce the number of blood cells in the bone marrow.

There are several treatments for the itching (pruritus) related to polycythemia vera. No single treatment has been found to be effective for all individuals. For mild cases, treatment may include avoiding triggers of itching and dry skin such as hot environment or bathing water. Several other treatments are available for more severe itching or itching that does not respond to initial treatments. Interferon-alpha is a medication that has been effective for reducing itching in a majority of individuals with PV who received this therapy, but there may be some side-effects to this treatment. Selective serotonin reuptake inhibitors, typically used to treat depression, may also reduce itching for some individuals with PV. If severe symptoms continue, medications targeting the causative gene, such as JAK inhibitors, may be helpful in reducing symptoms.

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