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.
In a myeloproliferative neoplasm Overview of Myeloproliferative Neoplasms In myeloproliferative neoplasms (myelo = bone marrow; proliferative = rapid multiplication; and neoplasm = new abnormal growth, such as a precancer or cancer), the blood-producing cells in the... read more , the blood-producing cells Formation of Blood Cells Red blood cells, most white blood cells, and platelets are produced in the bone marrow, the soft fatty tissue inside bone cavities. Two types of white blood cells, T and B cells ( lymphocytes)... read more in the bone marrow (precursor cells, also called stem cells) develop and reproduce excessively.
Polycythemia vera involves increased production of all types of blood cells Components of Blood The main components of blood include Plasma Red blood cells White blood cells Platelets read more : red blood cells, white blood cells, and platelets. Increased production of red blood cells is termed erythrocytosis Erythrocytosis Erythrocytosis is increased production of red blood cells (erythrocytes). (See also Overview of Myeloproliferative Neoplasms.) Erythrocytosis may be Primary: Caused by a disorder of the blood-forming... read more . 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.
Causes of Polycythemia Vera
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, the enzyme that 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 Myelofibrosis Myelofibrosis is a disorder in which fibrous tissue in the bone marrow replaces the blood-producing cells, resulting in abnormally shaped red blood cells, anemia, and an enlarged spleen. Myelofibrosis... read more with scarring and is less able to produce blood cells.
Symptoms of Polycythemia Vera
Often, people with polycythemia vera have no symptoms for years. The earliest symptoms usually are
Shortness of breath
Itching after a shower or bath
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 Erythromelalgia Erythromelalgia is a rare syndrome in which small arteries (arterioles) of the skin dilate periodically, causing a burning pain, making the skin feel hot, and making the feet and, less often... read more ). 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 Deep Vein Thrombosis (DVT) Deep vein thrombosis is the formation of blood clots (thrombi) in the deep veins, usually in the legs. Blood clots may form in veins if the vein is injured, a disorder causes the blood to clot... read more ), heart (causing a heart attack Acute Coronary Syndromes (Heart Attack; Myocardial Infarction; Unstable Angina) Acute coronary syndromes result from a sudden blockage in a coronary artery. This blockage causes unstable angina or a heart attack (myocardial infarction), depending on the location and amount... read more ), brain (causing a stroke Overview of Stroke A stroke occurs when an artery to the brain becomes blocked or ruptures, resulting in death of an area of brain tissue due to loss of its blood supply (cerebral infarction) and symptoms that... read more ), or lungs (causing pulmonary embolism Pulmonary Embolism (PE) Pulmonary embolism is the blocking of an artery of the lung (pulmonary artery) by a collection of solid material brought through the bloodstream (embolus)—usually a blood clot (thrombus) or... read more ). Blood clots may also block blood vessels that drain blood from the liver (Budd-Chiari syndrome Budd-Chiari Syndrome Budd-Chiari syndrome is caused by blood clots that completely or partially block blood flow from the liver. The blockage may occur anywhere from the small and large veins that carry blood from... read more ), 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 Essential Thrombocythemia Essential thrombocythemia is a myeloproliferative neoplasm in which excess platelets are produced, leading to abnormal blood clotting or bleeding. The hands and feet may burn, turn red, and... read more ). 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 Iron Deficiency Iron deficiency is a common cause of anemia, a condition in which the number of red blood cells is low. Iron deficiency usually results from loss of blood in adults (including bleeding from... read more may develop.
The liver and spleen may enlarge as both organs begin to produce blood cells (see also Enlarged Spleen Enlarged Spleen An enlarged spleen is not a disease in itself but the result of an underlying disorder. Many disorders can make the spleen enlarge. Many disorders, including infections, anemias, and cancers... read more ). 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.
The excess of red blood cells may be associated with stomach ulcers Peptic Ulcer Disease A peptic ulcer is a round or oval sore where the lining of the stomach or duodenum has been eaten away by stomach acid and digestive juices. Peptic ulcers can result from Helicobacter pylori... read more , gout Gout Gout is a disorder in which deposits of uric acid crystals accumulate in the joints because of high blood levels of uric acid (hyperuricemia). The accumulations of crystals cause flare-ups ... read more , and kidney stones Stones in the Urinary Tract Stones (calculi) are hard masses that form in the urinary tract and may cause pain, bleeding, or an infection or block of the flow of urine. Tiny stones may cause no symptoms, but larger stones... read more . Rarely, polycythemia vera progresses to leukemia Overview of Leukemia Leukemias are cancers of white blood cells or of cells that develop into white blood cells. White blood cells develop from stem cells in the bone marrow. Sometimes the development goes awry... read more .
Diagnosis of Polycythemia Vera
Genetic tests and other tests
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 Erythrocytosis Erythrocytosis is increased production of red blood cells (erythrocytes). (See also Overview of Myeloproliferative Neoplasms.) Erythrocytosis may be Primary: Caused by a disorder of the blood-forming... read more ). 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 to confirm the diagnosis of polycythemia vera. If those mutations are not found, doctors look for CALR and sometimes other mutations, which are also helpful in confirming the diagnosis.
Treatment of Polycythemia Vera
Removing blood (phlebotomy) to reduce the number of red cells
Drugs as needed to decrease the number of platelets, prevent complications, or relieve symptoms
With treatment, most people with polycythemia vera survive for decades. About 15% of people develop myelofibrosis Myelofibrosis Myelofibrosis is a disorder in which fibrous tissue in the bone marrow replaces the blood-producing cells, resulting in abnormally shaped red blood cells, anemia, and an enlarged spleen. Myelofibrosis... read more , and a small percentage can develop acute leukemia Overview of Leukemia Leukemias are cancers of white blood cells or of cells that develop into white blood cells. White blood cells develop from stem cells in the bone marrow. Sometimes the development goes awry... read more .
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 Blood Donation Process Healthy people donate a small amount of their blood to be used for blood transfusions. People usually give 1 pint (about 450 milliliters, approximately less than 1/10th of the total amount of... read more . 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 Stem cells from bone marrow Stem cell transplantation is the removal of stem cells (undifferentiated cells) from a healthy person and their injection into someone who has a serious blood disorder. (See also Overview of... read more is the only cure for polycythemia vera but is recommended only when polycythemia vera is complicated by myelofibrosis Myelofibrosis Myelofibrosis is a disorder in which fibrous tissue in the bone marrow replaces the blood-producing cells, resulting in abnormally shaped red blood cells, anemia, and an enlarged spleen. Myelofibrosis... read more 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 Phototherapy Psoriasis is a chronic, recurring disease that causes one or more raised, red patches that have silvery scales and a distinct border between the patch and normal skin. A problem with the immune... read more can help relieve itching.
The following is an English-language resource that may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
MPN Research Foundation: Polycythemia vera: supports research as well as advocacy and education for people with myeloproliferative neoplasms