Polycythemia vera (PV) is a myeloproliferative neoplasm and is characterized by the presence of an unusually high number of red blood cells in the body. A higher concentration of white blood cells and platelets may also be a factor in people with this condition. In PV patients, the blood is thicker than normal, causing slow blood flow and poor oxygenation. The primary complication of PV is the increased risk for thrombotic events (blood clots).
In both the United States and Europe, polycythemia vera is listed as a rare disease. PV usually presents around the age of 60 and occurrences are more frequent in men than women. Initially there is a long asymptomatic period in which most sufferers will discover an oddity in their routine blood work. It is a chronic disease with no cure and the primary goal is to control the level of red blood cells to reduce the risk of complications.
In rare cases the risk for this condition may run in families but is more commonly acquired during a person’s life. Mutations in the genes usually occur in the hematopoietic stem cell (cells that produce red blood cells) but these mutations can occur in the egg and sperm cells that pass on the information to their children.
Gene mutations in the JAK2 (Janus kinase 2) and TET2 (Ten-eleven translocation 2) genes have been associated with this condition. Not every person with a mutation in JAK2 or TET2 will develop Polycythemia vera but the risk is much higher for these individuals. The JAK2 gene provides the body with instructions to produce blood cells. Mutations in the gene can instruct this process to keep producing these cells even when the body has an adequate supply. This over production of red blood cells causes the blood to thicken and therefore can not travel through the bloodstream in an efficient manner. Less oxygen reaching the organs means reduced blood flow in the body causing organs like the spleen to swell requiring removal in some cases.
Symptoms will vary from person to person and all those who suffer with the disease may not have all the symptoms. Polycythemia vera symptoms can include headaches, tinnitus (ringing in the ears), dizziness and impaired vision. Incidences of pruritus (itching skin) or erythema (reddening of skin) have been associated with PV. The condition may cause an enlargement of the spleen (splenomegaly) and increase the risk for heart disease. Someone with PV may suffer from abdominal pain, angina (chest pain), acute leukemia and may be prone to bruise easily. Other symptoms may include weight loss, fatigue, sweating, facial flushing, cyanotic lips (blueish in color), ulcers, and hemorrhagic complications.
The kidneys release a hormone called erythropoietin that stimulates the production of red blood cells in the body. It is released in response to low oxygen levels in the blood, so anything that lowers the blood oxygen level will increase the amount of this hormone and stimulate red blood cell production. The kidneys continue to produce higher levels of the hormone until oxygen levels return to normal. The body begins to secrete lower levels of this hormone when it senses that red blood cell levels are too high. Low levels of erythropoietin in the blood along with mutations in either JAK2 or TET2 will warrant a diagnosis of polycythemia vera. If red blood cells do not show a mutation but the diagnosis is still suspected, a bone marrow biopsy can show mutations in the hematopoietic blood cells within the bone marrow.
The ratio between red blood cells and the total amount of blood in the body is called hematocrit. Risks for complications from the disease can be significantly decreased if the hematocrit is kept below 45%. The most common method of lowering the number of red blood cells in the body is a phlebotomy. A phlebotomy is the process of removing blood from the body through the veins. To reduce thickening of the blood, a low dose aspirin may be prescribed for the patient to take daily. If these treatments prove to be ineffective, hydroxyurea or interferon therapy may be prescribed, although they are only incorporated in cases of high risk PV. According to the most recent drug trials, these therapies presented a reduced quality of life with severe side effects that worsened as patients continued the treatment. Many of the participants realized no clear benefit to the therapy. In some cases, and usually as a last resort, a bone marrow transplant may be necessary.
Thrombotic events that can cause stroke or heart attack are the most dangerous complications of polycythemia vera and long-term prognosis depends heavily upon how well a patient responds to treatment. Deep vein thrombosis, or DVT, is a very dangerous type of blood clot which occurs in the veins located deep within the arms and legs. These clots can block the flow of blood in veins and arteries or travel to the lungs causing a pulmonary embolism. Clots can also increase the risk of a heart attack or stroke if they travel to the heart or brain. Other complications include petechiae (bleeding into the skin), epistaxis (nosebleeds) and bleeding gums.
In the later stages of Polycythemia vera, additional genetic mutations may cause this condition to transition into other diseases such as primary myelofibrosis, acute myeloid leukemia or myelodysplastic syndrome. Patients receiving treatment by phlebotomy alone have a life expectancy of 10 to 15 years, which is greatly improved over the initial 1 to 2 years from the time of diagnosis if left untreated.