Polycythemia vera

Primary polycythemia, often called polycythemia vera (PCV), polycythemia rubra vera (PRV), or erythremia, occurs when excess red blood cells are produced as a result of an abnormality of the bone marrow. Often, excess white blood cells and platelets are also produced. Polycythemia vera is classified as a myeloproliferative disease.

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Epidemiology

Polycythemia vera occurs in all age groups (including children),^[1] although the incidence increases with age. One study found the median age at diagnosis to be 60 years,^[2] while a study in Olmsted County, Minnesota found that the highest incidence was in people aged 70–79 years.^[3] The overall incidence in the Minnesota population was 1.9 per 100,000 person-years, and the disease was more common in men than women.^[3]

Symptoms

Patients with polycythemia vera are often asymptomatic. A classic symptom of polycythemia vera is generalized itching, particularly after exposure to warm water, which may be due to abnormal histamine release^[4][5] or prostaglandin production.^[6] Such itching is present in approximately 40% of patients with polycythemia vera.^[2] Gouty arthritis may be present in up to 20% of patients.^[2] Peptic ulcer disease is also common in patients with polycythemia vera; the reasons for this are unclear, but may be related to an increased susceptibility to infection with the ulcer-causing bacterium H. pylori.^[7]

A rare but classic symptom of polycythemia vera (and the related myeloproliferative disease essential thrombocythemia) is erythromelalgia.^[8] This is a sudden, severe burning pain in the hands or feet, usually accompanied by a reddish or bluish coloration of the skin. Erythromelalgia is caused by an increased platelet count or increased platelet "stickiness", resulting in the formation of tiny blood clots in the vessels of the extremity; it responds rapidly to treatment with aspirin.^[9][10]

Patients with polycythemia vera are prone to the development of blood clots (thrombosis). A major thrombotic complication (e.g. heart attack, stroke, deep venous thrombosis, or Budd-Chiari syndrome) may sometimes be the first symptom or indication that a person has polycythemia vera.

Diagnosis

Patients with polycythemia vera may often be asymptomatic. Physical exam findings are non-specific, but may include enlarged liver or spleen, plethora, or gouty nodules. The diagnosis is often suspected on the basis of laboratory tests. Common findings include an elevated hemoglobin level or hematocrit, reflecting the increased number of red blood cells; the platelet count or white blood cell count may also be increased. Because polycythemia vera results from an essential increase in erythrocyte production, patients have a low erythropoietin (EPO) level.

In primary polycythemia, there may be 8 to 9 million and occasionally 11 million erythrocytes per cubic millimeter of blood (a normal range for adults is 4-6), and the hematocrit may be as high as 70 to 80%. In addition, the total blood volume sometimes increases to as much as twice normal. The entire vascular system can become markedly engorged with blood, and circulation times for blood throughout the body can increase up to twice the normal value. The increased numbers of erythrocytes can cause the viscosity of the blood to increase as much as five times normal. Capillaries can become plugged by the very viscous blood, and the flow of blood through the vessels tends to be extremely sluggish.

Recently, in 2005, a mutation in the JAK2 kinase (V617F) was found by multiple research groups ^[11][12] to be strongly associated with polycythemia vera. JAK2 is a member of the Janus kinase family. This mutation may be helpful in making a diagnosis or as a target for future therapy.

As a consequence of the above, people with untreated PV are at a risk of various thrombotic events (deep venous thrombosis, pulmonary embolism), heart attack and stroke, and have a substantial risk of Budd-Chiari syndrome (hepatic vein thrombosis), or Myelofibrosis. The condition is considered chronic; no cure exists. Symptomatic treatment (see below) can normalize the blood count and most patients can live a normal life for years.

Treatment

As the condition cannot be cured, treatment focuses on treating symptoms and reducing thrombotic complications reducing the erythrocyte levels.

Bloodletting or phlebotomy is one form of treatment, which often may be combined with other therapies. The removal of blood from the body reduces the blood volume and brings down the hematocrit levels; in patients with polycythemia vera, this reduces the risk of blood clots. Phlebotomy is typically performed in people with polycythemia vera to bring their hematocrit (red blood cell percentage) down below 45 for men or 42 for women.^[13]

Low dose aspirin is often prescribed. Research has shown that aspirin reduces the risk for various thrombotic complications.

Chemotherapy for polycythemia may be used sparingly, when the rate of bloodlettings required to maintain normal hematocrit is not acceptable. This is usually with a "cytoreductive agent" (hydroxyurea, also known as hydroxycarbamide).

The tendency to avoid chemotherapy if possible, especially in young patients, is due to research indicating increased risk of transformation to AML, and while hydroxyurea is considered safer in this aspect, there is still some debate about its long-term safety.

In the past, injection of radioactive isotopes was used as another means to suppress the bone marrow. Such treatment is now avoided due to a high rate of AML transformation.

Other therapies include interferon injections, and in cases where secondary thrombocytosis (high platelet count) is present, anagrelide may be prescribed.

Bone marrow transplants are rarely undertaken in polycythemia patients - since this condition is non-fatal if treated and monitored, the benefits rarely outweigh the risks involved in such a procedure.

References