Polycythemia vera is due to mutations in the Janus kinase 2 (JAK2) gene, which produces a protein (enzyme) that stimulates excessive production of blood cells.
People may feel tired and weak, light-headed, or short of breath, or develop symptoms caused by blood clots.
Blood tests are done for diagnosis.
Phlebotomy is done to remove excess red blood cells, and some people take aspirin and sometimes other drugs.
Polycythemia vera involves increased production of all types of blood cells: red blood cells, white blood cells, and platelets. Increased production of red blood cells is termed erythrocytosis. Sometimes people with polycythemia vera have only increased red blood cell production, but usually increased red blood cell production by itself is due to another cause.
In polycythemia vera, the excess of red blood cells increases the volume of blood and makes it thicker, so that it flows less easily through small blood vessels.
Polycythemia vera occurs in about 2 in every 100,000 people. The average age at which the disorder is diagnosed is 60, but it also occurs in people younger than 40. More men than women develop polycythemia vera over age 60, but more women than men develop the disease under age 40.
More than 95% of people with polycythemia vera have a mutation in the JAK2 gene. This mutation causes excess blood cell production.
In addition, mutations in the calreticulin gene (CALR) and other genes have been found in some people with polycythemia vera. These mutations lead to sustained activation of JAK2 kinase, which causes excess red blood cell production.
Blood cells are normally produced in the bone marrow. Sometimes the spleen and liver also start producing blood cells. Eventually, in a small percentage of people, the bone marrow develops myelofibrosis with scarring and is less able to produce blood cells.
Often, people with polycythemia vera have no symptoms for years. The earliest symptoms usually are
Vision may be distorted, and people may have blind spots or see flashes of light (ocular migraine).
People may have bleeding from the digestive tract or gums and more bleeding than would be expected from small cuts.
The skin, especially the face, may look red. People may itch all over, particularly after bathing or showering. People may have redness and burning sensations in the hands and feet (erythromelalgia). More rarely, bone pain may be felt.
A blood clot sometimes causes the first symptoms. The increase in red blood cells in polycythemia vera makes the blood thicker and more likely to clot more than normal. A clot may form in almost any blood vessel, including those of the arms, legs (causing deep vein thrombosis), heart (causing a heart attack), brain (causing a stroke), or lungs (causing pulmonary embolism). Blood clots may also block blood vessels that drain blood from the liver (Budd-Chiari syndrome), particularly in young women.
In some people, the number of platelets (cell-like particles in the blood that help the body form blood clots) increases (thrombocythemia). Although an increased number of platelets might be thought to always cause excessive blood clotting, in people with polycythemia vera, a very high number of platelets can actually cause bleeding by affecting other parts of the body's clotting system.
In some people, iron deficiency may develop.
The liver and spleen may enlarge as both organs begin to produce blood cells (see also Enlarged Spleen). As the liver and spleen enlarge, a sense of fullness in the abdomen may develop. Pain can suddenly become intense should a blood clot develop in blood vessels of the liver or spleen, causing parts of it to die.
Polycythemia vera may be discovered through a blood count done for another reason, even before people have any symptoms. The number of red blood cells, the level of the protein that carries oxygen in red blood cells (hemoglobin) and the percentage of red blood cells in the total blood volume (the hematocrit) are abnormally high. The number of platelets and white blood cells may also be increased.
Doctors consider polycythemia vera a possibility if the hematocrit is very high. However, the diagnosis cannot be based solely on the hematocrit result. Once the increase in the red blood cell count (polycythemia) is discovered, doctors must determine whether the person has polycythemia vera or polycythemia caused by some other condition (secondary erythrocytosis). The medical history and examination may help differentiate between polycythemia vera and secondary erythrocytosis, but doctors must usually investigate further.
Blood levels of erythropoietin, a hormone that stimulates the bone marrow to produce red blood cells, also may be measured. Levels of erythropoietin are usually, extremely low in polycythemia vera, and they are often, but not always, normal or high in secondary erythrocytosis.
People are tested for JAK 2 gene mutations. If those mutations are not found, doctors look for CALR mutations.
Treatment does not cure polycythemia vera, but it can control it and decrease the likelihood of complications, such as the formation of blood clots. The aim of treatment is to decrease the number of red blood cells. Usually, blood is removed from the body in a procedure called phlebotomy, which is similar to the way blood is removed when donating blood. Up to a pint (about a half liter) of blood is removed every other day until the hematocrit reaches a normal level. Then blood is removed as needed to maintain the hematocrit at a normal level, for example, every 1 to 3 months.
Aspirin can help relieve symptoms related to the high platelet counts, such as migraines that affect vision and burning pain and redness of the hands and feet. However, aspirin has not been proven to decrease the risk of blood clots in polycythemia vera and does not benefit people who do not have symptoms
People who continue to have symptoms after having phlebotomy may need other treatments. For such people, doctors may use ruxolitinib, a drug that inhibits the activity of JAK2 , or other drugs, including pegylated interferon alfa-2b, anagrelide, or hydroxyurea.
Bone marrow transplantation is the only cure for polycythemia vera but is recommended only when polycythemia vera is complicated by myelofibrosis and bone marrow failure. Bone marrow transplantation is usually recommended as soon as there are signs of myelofibrosis in the bone marrow.
Other drugs can help control some of the symptoms. For example, antihistamines, selective serotonin reuptake inhibitors (SSRIs),, or PUVA light therapy can help relieve itching.