Last updated:
3/10/2026
Years published: 1986, 1990, 1994, 1995, 1997, 1998, 2005, 2008, 2011, 2013, 2016, 2018, 2023, 2025, 2026
NORD gratefully acknowledges Ayalew Tefferi, MD, Professor of Medicine and Hematology, Mayo Clinic, and Gioconda Alyea, MD (FMG), MS, National Organization for Rare Disorders, for assistance in the preparation of this report.
Summary
Polycythemia vera (PV) is a rare, chronic condition in which the bone marrow produces too many blood cells (myeloproliferation). The bone marrow is the soft tissue inside bones where blood cells are made. In PV, the body makes too many red blood cells, and many people also have higher than normal numbers of white blood cells and platelets.
Because red blood cells are produced in excess, the number of red blood cells circulating in the bloodstream becomes abnormally high. This can cause the blood to become thicker and increase in volume, a condition known as hyperviscosity. Thicker blood may not flow as easily through small blood vessels, which can affect normal circulation.
People with PV may experience a range of symptoms. These can include headaches, fatigue, weakness, dizziness, itching of the skin (especially after warm baths or showers), and an enlarged spleen (splenomegaly). Some people may also have digestive problems. In addition, PV increases the risk of developing blood clots, which can block blood flow to important organs.
More than 90% of people with PV have a change (variant) in the JAK2 gene. Treatment includes phlebotomy, a procedure that removes blood from the body to reduce the number of red blood cells, along with medications to help control blood cell production and reduce complications.
Introduction
PV was first reported in medical literature in 1892. At that time, and for many years after, doctors grouped PV with similar conditions under the term “myeloproliferative disorders” (MPDs). This term was first used to describe polycythemia vera and related disorders in 1951. These were diseases in which the bone marrow made too many blood cells.
In 2008, the World Health Organization reclassified MPDs to “myeloproliferative neoplasms” (MPNs) to reflect the consensus that these diseases are blood cancers (neoplasms). MPNs are characterized by the overproduction (proliferation) of one or more of the three main blood cell lines, red or white blood cells or platelets. Red blood cells carry oxygen to the body. White blood cells fight infection. Platelets are involved in clotting blood in response to injury.
In addition to PV, three other disorders are commonly classified as MPNs, chronic myeloid leukemia, essential thrombocythemia, and primary myelofibrosis. Because MPNs involve uncontrolled growth of blood-forming cells, they are also considered a form of blood cancer.
The symptoms of polycythemia vera (PV) usually develop slowly over many years. Often, the disorder is found on a blood test as part of a routine exam before noticeable symptoms occur. Occasionally, affected individuals may report vague, nonspecific symptoms that eventually lead to diagnosis of the disorder.
Many people with PV slowly develop a variety of general, nonspecific symptoms that are common to many disorders such as:
Additional symptoms may occur in some affected individuals including blurred vision, ringing in the ears (tinnitus), and abnormal redness of the skin, especially on the face.
Eventually, the spleen becomes involved. The spleen is an organ located in the upper left part of the abdomen that filters out worn-out blood cells. The spleen often becomes abnormally enlarged in individuals with PV as it attempts to clear a greater number of blood cells than normal, a condition called splenomegaly. Splenomegaly may cause an affected individual to have a bloated or full feeling in the abdomen.
Less common symptoms associated with PV include:
Some individuals with PV may develop symptoms because their blood is thicker than normal and doesn’t flow as easily. They may experience abnormalities affecting the platelets, which can increase a person’s risk of developing blood clots. Complications that occur due to blood clots may be referred to as thrombotic events and, in rare cases, can be the first obvious sign of PV. Specific symptoms depend upon where a blood clot forms.
A blood clot can cause a stroke, chest pain (angina), a heart attack, deep vein thrombosis (DVT), or a pulmonary embolism.
DVT occurs when a blood clot forms in the legs may cause the legs to become painful and swollen.
Pulmonary embolism occurs when a clot forms in the lungs, or when a piece of a DVT breaks off and travels through the bloodstream, eventually becoming stuck in the pulmonary artery.
A pulmonary embolism can cause breathlessness, sudden pain in the chest, exhaustion, or life-threatening complications such as high blood pressure of the pulmonary artery.
Some individuals with PV have developed Budd-Chiari syndrome, a condition in which a blood clot forms in the main blood vessel leading to the liver (hepatic vein thrombosis). Symptoms of Budd-Chiari syndrome include:
The abnormal rapid increase (proliferation) of red blood cells may also cause peptic ulcers (sores on the lining of the stomach or duodenum), gout (a painful form of arthritis caused by high levels of uric acid in the blood), and kidney stones (caused by abnormally high levels of uric acid).
Over many years, PV can “burn out” or progress to a “spent phase.” In this phase, the bone marrow becomes scarred and can no longer make normal amounts of blood cells. When this occurs, the bone marrow can no longer produce blood cells, resulting in:
In rare cases, PV may eventually progress into a form of aggressive blood cancer (leukemia) known as acute myeloid leukemia (AML).
In the spent phase, PV resembles idiopathic myelofibrosis, which is a chronic blood cancer where the bone marrow is gradually replaced by scar tissue which reduces its ability to make blood cells and causes symptoms like fatigue, enlarged spleen, and bone pain.
Polycythemia vera (PV) begins when a single blood-forming cell in the bone marrow develops a change (variant) in its genetic material (DNA). Because all the abnormal blood cells come from this one altered cell, PV is called a clonal disorder. The bone marrow is the soft, spongy tissue inside bones where most blood cells are made. The underlying reason why this first genetic change occurs is not known, but it is not inherited and develops after birth.
About 95% of people with PV have a specific change (variant) in the JAK2 gene, most often the JAK2 V617F variant. The JAK2 gene normally helps control when the bone marrow makes new blood cells. This small DNA change alters how the JAK2 protein, an enzyme (kinase) that helps regulate blood cell production, functions. Normally, JAK2 becomes active only when the body signals the marrow to make new blood cells. With the V617F variant, the “on/off switch” is broken,the signal to make blood cells stays permanently turned on, even when the body does not need more blood cells.
This continuous activation sends ongoing growth signals inside the cell, causing blood-forming cells to multiply and survive longer than normal. In polycythemia vera, this effect is most pronounced in the pathway that produces red blood cells, leading to excessive red blood cell production and unusually high levels of hemoglobin. Hemoglobin is the iron-containing protein in red blood cells that carries oxygen from the lungs to the rest of the body. White blood cells and platelets may also be produced in greater amounts, although usually to a lesser extent.
The original defective cell in PV is a hematopoietic stem cell, the type of cell that produces all blood cell types, red cells, white cells, and platelets. Once this stem cell acquires the JAK2 variant, it continually reproduces itself and eventually becomes the dominant cell population in the bone marrow. These abnormal cells grow without normal controls, such as erythropoietin (EPO), a hormone produced by the kidneys that typically regulates red blood cell production.
As these abnormal blood-forming cells expand and crowd the bone marrow, they can also release inflammatory substances, including IL-6 and TNF-α, which change the marrow environment. This chronic (long-term) inflammation may lead to scar tissue (fibrosis) in the bone marrow.
Although PV usually happens by chance, there have been reports of families with multiple affected members, suggesting that inherited factors beyond the JAK2 variant may contribute to the disease development. However, no strong pattern of hereditary transmission has been identified.
The symptoms of PV come from the overproduction of red blood cells, and sometimes white blood cells and platelets, which disrupt normal blood formation and circulation.
Polycythemia vera (PV) affects slightly more males than females. In the United States, it is estimated to occur in about 44 to 60 per 100,000 people in the US. It is most often diagnosed in people more than 60 years old but can affect individuals of any age. It is extremely rare in people under age 20.
Polycythemia vera (PV) is diagnosed using a combination of a thorough medical exam, a detailed patient health history, and specific lab tests.
In many people, the disorder may be detected from blood tests conducted during routine blood work. A complete blood count (CBC) may show too many red blood cells and sometimes an increased number of white blood cells and platelets.
Doctors also look at:
If either of these measures is elevated, PV may be a possibility.
Physicians may also measure the levels of erythropoietin (EPO), a hormone that causes the bone marrow to produce red blood cells. In individuals with PV, EPO levels are abnormally low. This test is usually done to distinguish PV from secondary polycythemia, in which EPO levels are not affected. This helps doctors tell the two conditions part.
In some people with PV, a bone marrow biopsy may be performed. During this procedure, a small sample of bone marrow tissue is removed and examined under a microscope. The sample is used to evaluate how well the bone marrow is functioning and whether it is producing blood cells normally. A bone marrow biopsy can help confirm the diagnosis, although it is not always required.
A strong suspicion of PV is raised when:
A variety of specialized tests can be used to identify JAK2 gene variants in blood cells, which are present in most people with PV.
Treatment
The treatment of polycythemia vera (PV) focuses on lowering the number of red blood cells and preventing complications, especially blood clots (thrombosis), which can interfere with normal blood flow and lead to serious problems like strokes or heart attacks. The main goals of treatment are to keep blood flowing normally, reduce symptoms, and avoid long-term damage. Most people are treated with phlebotomy and various medications.
Patients with PV are often classified as low-risk or high-risk for developing blood clots. Low-risk patients are generally younger than 60 years of age and have not had a previous blood clot. For these individuals, initial treatment typically consists of managing cardiovascular risk factors, low-dose aspirin (81–100 mg daily), and phlebotomy to maintain hematocrit below 45 percent. Cytoreductive therapy, which refers to medications that reduce blood cell production, is generally not recommended as initial treatment for low-risk patients. However, if certain complications develop, such as new thrombosis, disease-related major bleeding, frequent or poorly tolerated phlebotomy, splenomegaly, progressive thrombocytosis or leukocytosis, or persistent symptoms such as itching, night sweats, or fatigue, cytoreductive therapy may be started.
For many people with PV, the first treatment is phlebotomy, a procedure in which blood is drawn from the body at regular intervals, often over several months. This helps reduce the number of red blood cells in circulation, thinning the blood and easing symptoms caused by its thickened consistency. Treatment aims to maintain the hematocrit (the percentage of blood made up of red blood cells) below 45%, which has been shown to reduce the risk of blood clots. In some people, phlebotomy may be the only treatment needed for many years. However, it does not treat other issues associated with PV, such as high platelet levels (thrombocythemia), high white blood cell counts (leukocytosis), persistent itching, or gout. In some cases, repeated phlebotomy may even contribute to an increase in platelet levels.
People considered high risk, generally those over age 60 or those who have previously experienced a blood clot, usually require cytoreductive therapy in addition to phlebotomy and low-dose aspirin. Cytoreductive therapy helps control the production of blood cells in the bone marrow.
When phlebotomy alone is not enough, or if additional control of blood cell production is needed, medications are often used. These include:
Other drugs in development are being actively investigated and represent potential future options for patients with PV:
Some older medications, such as busulfan, chlorambucil, and radioactive phosphorus, were used in the past but are now rarely recommended due to their potential long-term risks, including an increased chance of developing leukemia.
In the advanced stages of PV, some individuals may enter what is known as the “spent phase.” During this phase, the bone marrow becomes scarred and stops producing enough healthy blood cells (causing anemia). People may require periodic blood transfusions to maintain adequate levels of red cells. The spleen, which often becomes enlarged and painful during this stage, may need to be removed in a surgical procedure known as a splenectomy if symptoms become severe.
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Hassanien D, AlYafei RA, Metwally OH, et al. Advances in polycythemia vera treatment with targeted therapies and clinical trials. Discov Oncol. 2025;16(1):1970. Published 2025 Oct 27. doi:10.1007/s12672-025-03703-9
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INTERNET
Cortese T. FDA Gives Fast Track Designation to Givinostat for Polycythemia Vera. Cancer Network. May 6, 2025. Available at: https://www.cancernetwork.com/view/fda-gives-fast-track-designation-to-givinostat-for-polycythemia-vera Accessed on 3/9/2026.
Spindler S. Rusfertide Nearly Eliminates Need for Phlebotomies to Treat Polycythemia Vera. National Cancer Institute. March 28, 2024. Available at: https://www.cancer.gov/news-events/cancer-currents-blog/2024/rusfertide-polycythemia-vera-fewer-phlebotomies Accessed on 3/9/2026.
Nagalla S and Besa EC, Polycythemia Vera. Medscape. Updated: September 11, 2024. Available at: https://www.emedicine.com/MED/topic1864.htm Accessed on 3/9/2026.
Mayo Clinic for Medical Education and Research. Polycythemia Vera. May 8, 2025. Available at: https://www.mayoclinic.com/health/polycythemia-vera/DS00919 Accessed on 3/9/2026.
Leukemia & Lymphoma Society. Polycythemia Vera Facts. Revised April 2015. Available at: https://bloodcancerunited.org/blood-cancer/myeloproliferative-neoplasms-mpns/polycythemia-vera-pv Accessed on 3/9/2026.
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