Information on the following diseases can be found in the Related Disorders section of this report:

• Leukemia

The symptoms and physical findings associated with polycythemia vera vary greatly from case to case. The disease tends to develop slowly, and symptoms may not be noticeable at first.

Affected individuals may experience fatigue, difficulty concentrating, headaches, drowsiness, forgetfulness, dizziness (vertigo), and ringing in the ears (tinnitus). They may also experience redness of the skin, especially of the face, and, in 50 percent of cases, abnormal itchiness (pruritis), particularly after a hot bath. In some cases, affected individuals have an abnormally enlarged spleen (splenomegaly) and/or liver (hepatomegaly). Other symptoms may include shortness of breath and difficulty breathing when lying down.

Individuals with polycythemia vera may have other complications including high blood pressure (hypertension), the formation of blood clots (thrombosis), and/or rupturing of and loss of blood (hemorrhaging) from certain blood vessels. If left untreated, thrombosis may involve the liver, heart, lungs, and/or brain.

In come cases, polycythemia vera may be associated with Budd-Chiari syndrome, a rare disorder characterized by narrowing and obstruction (occlusion) of the veins of the liver (hepatic veins). Symptoms associated with Budd Chiari syndrome include pain in the upper right part of the abdomen, an abnormally large liver (hepatomegaly), and/or accumulation of fluid in the space (peritoneal cavity) between the two layers of the membrane that lines the stomach (ascites). (For more information on this disorder, choose "Budd Chiari" as your search term in the Rare Disease Database).

The number, volume, and mass of red blood cells can be so great (erythrocytosis) that the blood becomes thick and slow flowing (hyperviscicity). In such cases, the potential for heart attack or stroke may be increased.

Other symptoms may include vision abnormalities, skin discoloration (a bluish tone), numbness, and fatigue.

The cause of this disorder is not known. It is considered an acquired disorder (not present at birth).

Polycythemia vera is one of the family of disorders known as myeloproliferative disorders. This name refers to improper function of the bone marrow, where blood cells are formed. The myeloproliferative disorders also include essential thrombocythemia, agnogenic myeloid metaplasia, secondary myelofibrosis, and chronic myelogenous leukemia. There is similarity among these disorders, and transition from one to another is possible.

Polycythemia vera is a relatively rare disorder that occurs in about one in 100,000 people. It is primarily a disease of middle-aged or elderly people, although it does occasionally occur among younger adults and even among children. It occurs more frequently in men than in women. Polycythemia vera was first described in the medical literature in 1892 (H. Vaquez).

Budd-Chiari syndrome is a rare disorder characterized by narrowing and obstruction (occlusion) of the veins of the liver (hepatic veins). Symptoms include pain in the upper right part of the abdomen, an abnormally large liver (hepatomegaly), and/or accumulation of fluid in the space (peritoneal cavity) between the two layers of the membrane that lines the stomach (ascites). Additional findings that may be associated with the disorder include nausea, vomiting, and/or an abnormally large spleen (splenomegaly). The severity of the disorder varies from case to case, depending upon the site and number of affected veins. In some cases, if the major hepatic veins are involved, high blood pressure in the veins carrying blood from the gastrointestinal (GI) tract back to the heart through the liver (portal hypertension) may be present. In most cases, the exact cause of Budd-Chiari syndrome is unknown.

Chronic myelogenous leukemia is a rare myeloproliferative disorder characterized by the excessive development of white blood cells in the spongy tissue found inside large bones of the body (bone marrow), spleen, liver and blood. As the disease progresses, the leukemic cells invade other areas of the body including the intestinal tract, kidneys, lungs, gonads and lymph nodes.

There are two phases to chronic myelogenous leukemia. The first phase, or chronic phase, is characterized by a slow, progressive overproduction of white blood cells. An advanced phase is called the acute phase or blast crisis. At this point, over 50 percent of the cells in the bone marrow are immature malignant cells (blast cells or promelocytes). In the acute phase, the leukemia is very aggressive and does not respond well to therapy. Approximately 85 percent of all individuals with chronic myelogenous leukemia enter the acute phase.

Essential thrombocythemia is characterized by overproduction of the precursor cells to blood platelets (megakaryocytes) which, in turn, leads to a vastly increased number of platelets in the blood. Platelets are specialized cells in blood essential for the normal process of clotting. In addition to overproduction of platelets, other symptoms and signs of ET may include an enlarged spleen (splenomegaly); bleeding from the gut, gums and/or nose (hemorrhaging); and constricted or blocked arteries (thrombosis).

Agnogenic myeloid metaplasia (AMM) with myelofibrosis, (primary idiopathic myelofibrosis, myelosclerosis) is caused by a defect in a stem cell that results in the overproduction of red blood cells, white blood cells, and platelets (panmyelosis), progressive bone marrow fibrosis and splenomegaly. It usually presents during the years of middle age or among those who are elderly. It only very rarely affects younger people. Agnogenic myeloid metaplasia with myelofibrosis appears to affect males and females in equal numbers and proportions.

Diagnosis
Frequently the first indication that polycythemia vera is present in a patient is the discovery of a large or high red blood cell count while looking for other symptoms. The attentive physician will be alerted sufficiently to examine cells taken from the bone marrow and the blood. Such physical examination combined with laboratory tests leads generally to the correct diagnosis.

Treatment
Treatment is aimed at controlling the symptoms and decreasing the risk of complications, especially blood clotting and hemorrhage.

To reduce the volume of circulating red blood cells, blood is drawn from the patient (phlebotomy) as if the patient were donating blood. Blood may be drawn at regular intervals over a period of several months. The procedure may be repeated several times at intervals of several months.

Phlebotomy may be combined with drug therapy. The drug hydroxyurea is often used in conjunction with phlebotomy. Hydroxyurea suppresses the activity of cells in the bone marrow (myelosuppressive), reducing the rate of production of blood components.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com.

Studies currently listed (2005) on the www.clinicaltrials.gov web site include the following. For information on these studies, contact the NIH Patient Recruitment office listed above or go to the web site:

A study of the effect of the anti-cancer drug imatinib (Gleevec) on the condition of patients with, among other disorders, polycythemia vera.

A study of the effect of the anti-cancer drug Gleevec (imatinib) on the condition of patients with, among other disorders, myelofibrosis.

A study of the effect of low-dose, total-body irradiation in combination with at least two chemotherapeutic agents, followed by stem cell transplantation in patients with polycythemia vera, among other myeloproliferative disorders.

McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Polycythemia vera. Entry Number; 263300: Last Edit Date; 11/4/2004.

McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Neutrophil-Specific Antigen 1. Entry Number; 162860: Last Edit Date; 8/1/2002.

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Hoffman R, Benz Jr EJ, Shattil SJ et al., eds. Hematology: Basic Principles and Practice. 2nd ed. Churchill-Livingstone, Inc. New York, NY; 1995:1121-38.

REVIEW ARTICLES
Elliot MA, Tefferi A. Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia. Br. J. Haematol. 2005;128:275-90.

Pahl HL. Diagnostic approaches to polycythemia vera in 2004. Expert Rev Mol Diagn. 2004;4:495-502.

Chomienne C, Rain JD, Briere JD, et al. Risk of leukemic transformation in PV and ET patients. Pathol Biol (Paris). 2004;52:289-93.

Fruchtman SM. Treatment paradigms in the management of myeloproliferative disorders. Semin Hematol. 2004;41(2 Suppl 3):18-22.

Barbui T. The leukemia controversy in myeloproliferative disorders: is it a natural progression of disease, a secondary sequela of therapy, or a combination of both? Semin Hematol. 2004;41(2 Suppl 3)15-17.

Michiels JJ, Berneman ZN, Schroyens W, et al. Pathophysiology and treatment of platelet-mediated microvascular disturbances, major thrombosis and bleeding complication in essential thrombocythemia and polycythemia vera. Platelets. 2004;15:67-84.

Stuart BJ, Viera AJ. Polycythemia vera. Am Fam Physician. 2004;69:2139-44.

Spivak JL, Barosi G, Tognoni G, et al. Chronic myeloproliferative disorders. Hematology (Am Soc Hematol Educ Program). 2003;:200-24.

Zarkovic M, Kwaan HC. Correction of hyperviscosity by apheresis. Semin Thromb Hemost. 2003;29:535-42.

Kwaan HC, Wang J. Hyperviscosity in polycythemia vera and other red cell abnormalities. Semin Thromb Hemost. 2003;29:451-58.

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