Polycythemia Vera

Polycythemia (Rubra) Vera

What is it?

Polycythaemia (Rubra) Vera, also known as primary polycythaemia vera, is a disorder where too many red cells are produced in the bone marrow, without any identifiable cause. These cells accumulate in the bone marrow and in the blood stream where they increase the blood volume and cause the blood to become thicker, or more 'viscous' than normal. In many people with polycythaemia vera, too many platelets and white cells are also produced.

Polycythaemia vera is a rare chronic disease diagnosed in an estimated 2 to 3 people per 100,000 population. Although it can occur at any age, polycythaemia vera usually affects older people, with most patients diagnosed over the age of 55 years. Polycythaemia vera is rare in children and young adults. It occurs more commonly in males than in females.

Symptoms and Complications 

Many people have no symptoms when they are first diagnosed with polycythaemia vera. The disease is often discovered during a routine blood test or physical examination. 

If symptoms do develop, they tend to do so over time. . They are mainly due to the increased thickness (hyperviscosity) and abnormally high numbers of blood cells in the circulating blood. Common symptoms include headaches, blurred vision, fatigue, weakness, dizziness, itchy skin and night sweats.

Enlargement of the spleen (splenomegaly) is also common and occurs in around 75 per cent of cases. Symptoms include feelings of discomfort, pain or fullness in the upper left-side of the abdomen. An enlarged spleen may also cause pressure on the stomach causing a feeling of fullness, indigestion and a loss of appetite. In some cases the liver may also be enlarged.This is called hepatomegaly.

Some people experience gout, which usually presents as a painful inflammation of the big toe or foot. This can result from a build up of uric acid, a byproduct of the increased production and breakdown of blood cells. Some individuals may develop erythromelalgia, a rare condition that primarily affects the feet and, less commonly, the hands. It is characterised by intense, burning pain of affected extremities, and increased skin temperature that may be episodic or almost continuous in nature.

In many cases, people with polycythaemia vera have a ruddy (red) complexion, and a reddening of the palms of the hand and soles of the feet, ear lobes, mucous membranes and the eyes. This is due to the high numbers of red cell in the circulation. A raised blood pressure (hypertension) is also common.

Blood clots (thrombosis) and bleeding

Blood clots are a common complication of polycythaemia vera and occur in around 30 per cent of people, even before they are diagnosed. As the blood is thicker than normal it cannot flow as easily, especially through the smaller blood vessels. If left untreated, this increases the risk of thrombosis, the formation of a blood clot within a blood vessel. Blood clots can form in various parts of the body including the deep and superficial veins of the legs, in the heart (causing a myocardial infarction or heart attack) and in the brain (causing a stroke). Older people and those with a history of a previous blood clot are at increased risk. A major aim of treatment in polycythaemia vera is to maintain a normal blood count and reduce your risk of thrombosis.

Bleeding and easy bruising can also occur. This is usually minor and occurs in around one quarter of all patients.

Occasionally bleeding into the gut can be prolonged or severe.

How is Polycythaemia Vera diagnosed?

Polycythaemia vera is diagnosed using a combination of laboratory tests and a physical examination.

Full blood count

People with polycythaemia vera have a high red cell count, haemoglobin level and haematocrit (>52 % in men or >48% in females) due to the excessive production of red cells. The haematocrit is the percentage of the whole blood that is made up of red cells. A raised white cell count (especially a raised neutrophil count) and a raised platelet count are also common findings.

The red cell mass is the total number of red cells circulating in your blood. Polycythaemia vera may be diagnosed when the red cell mass is 25% greater than the average normal expected value. Other findings that help confirm the diagnosis of polycythaemia vera include an enlarged spleen (splenomegaly) and the presence of the JAK2 mutation or other cytogenetic abnormalities in your blood or bone marrow cells.

JAK2 Mutation testing

JAK2 mutations (particularly the V617F mutation) can be found in more than 95% of people with Polycythaemia vera. This test can be performed on a blood sample and will help to confirm the diagnosis of a myeloproliferative neoplasm. It doesn't help distinguish polycythaemia vera from essential thrombocythaemia or primary myelofibrosis.

Bone marrow examination

In polycythaemia vera the bone marrow is often very active with abnormally high numbers of normal cells. Iron stores may be depleted since iron is being used to make more and more red cells.

Other possible blood tests

• serum vitamin B-12 levels
• uric acid levels
• erythropoietin levels
• coagulation studies (to see if your blood is clotting normally)
• blood oxygen levels

Other possible tests

• Chest X-ray – to rule out lung disease
• Abdominal ultrasound and / or CT scan – to rule out kidney disease and measure spleen / liver size

How is Polycythaemia Vera treated?

The goal of treatment for polycythaemia vera is to reduce the number of cells in your blood and help you to maintain a normal blood count. This helps control any symptoms of your disease and reduces the risk of complications due to blood clotting, or bleeding. The treatment, or combination of treatments chosen for you will depend on several factors including the duration and severity of your disorder, whether or not you have a history of blood clots, your age and your general health.

Venesection

Venesection (or phlebotomy) is a procedure in which a controlled amount of blood is removed from your bloodstream. This procedure is commonly used when people are first diagnosed with polycythaemia vera because it can help to rapidly reduce a high red cell count. In a process similar to a blood donation, 450mls to 500mls of your blood is removed, usually from a large vein in the arm, inside the elbow bend. This is usually done in the outpatient's department of the hospital. It takes about 30 minutes to complete. You will need to have a blood test before to check your blood count, and you must make sure you drink plenty of water before and after the procedure.

This procedure may need to be repeated frequently at first, usually every few days, until your haematocrit is reduced to the desired level. After this, you may need to have the procedure repeated periodically, for example at monthly intervals, to help maintain a normal blood count.\For many people, particularly younger patients and those with mild disease, regular venesection (every few months) may be all that is needed to control their disease for many years.

Many people with polycythaemia vera also need other treatments in addition to, or instead of venesection, to help control their blood count.

Myelosuppressive Drugs

Myelosuppressive (bone marrow suppressing) drugs or chemotherapy are commonly used to reduce blood cell production in the bone marrow. These drugs are commonly used for people with an extremely high platelet count, complications due to blood clotting or bleeding, or symptoms of an enlarged spleen. They are also used for some people who are unable to tolerate venesection or whose disease is no longer responding to venesection.

The most commonly used myelosuppressive agent is a chemotherapy drug called hydroxyurea. It is particularly useful in controlling a high platelet count (thrombocytosis) and therefore reducing the risk of thrombosis. Hydroxyurea is taken in the form of a capsule at home every day. As hydroxyurea is a chemotherapy drug, it is known to affect fertility and should be avoided during pregnancy, for it can cause harm or may be fatal to the foetus. If this could be an issue for you, you should ask your haematologist about your options. 

Another less commonly used chemotherapy drug is busulphan. This drug is also given in tablet form.

Chemotherapy taken in capsule form is tolerated well by most people and side effects tend to be few and mild. As these drugs work by suppressing blood formation, periodic blood tests should be performed when taking these drugs to monitor the blood count and to guard against severe reductions in the white cell or platelet counts. There is a very small risk of developing leukaemia later on in people who receive some chemotherapy for prolonged periods of time. It is still unclear whether there is a very small increase in the risk of leukaemia in people receiving hydroxyurea and this must be weighed against the potentially serious complications of uncontrolled disease (thrombosis). Discuss with your doctor if this is a concern to you.

Interferon

Interferon is a substance produced naturally by the body's immune system. It plays an important role in fighting disease. In polycythaemia vera, interferon is sometimes prescribed for younger patients to help control the production of blood cells. Interferon is usually given three times a week as an injection under the skin (subcutaneous injection) using a very small needle. You or a family member (or friend) will be taught how to do this at home. A weekly injection is now available and is becoming more widely used.

Side effects of interferon can be unpleasant but they can be minimised by starting with a small dose, and building up to the full dose over several weeks. The main side-effects are flu-like symptoms such as chills, fevers, aches and pains and weakness. Your doctor or nurse will explain any side effects you might experience while you are having these treatments and how they can be managed.

Aspirin

Many people are prescribed small daily doses of aspirin, which have been shown to significantly reduce the risk of thrombosis in people with polycythaemia vera. Aspirin works by preventing your platelets from clumping together to form harmful blood clots in different parts of your body. Aspirin can irritate the lining of the stomach which can result in pain or discomfort in the stomach, causing nausea, heartburn or loss of appetite. Taking your aspirin with food or milk may help prevent this. In addition, many people are prescribed specially coated aspirin that allows the drug to pass through the stomach and into the intestine before being dissolved. This helps to reduce the risk of stomach upset. You should see your doctor if you are experiencing stomach upset while on aspirin.

Aspirin is taken at home in tablet form. Drug interactions can occur, so it is important to avoid taking other medications while you are on aspirin, unless you are advised to do so by your doctor.

Anagrelide hydrochloride

Anagrelide hydrochloride (Agrylin®) is a drug used to reduce high platelet counts in people with polycythaemia vera and essential thrombocythaemia. Anagrelide affects platelet-producing cells in the bone marrow called megakaryocytes, slowing down platelet production and therefore reducing the number of platelets in the circulating blood. This can help to reduce symptoms and the risk of clotting complications in the future. Although anagrelide lowers platelet counts to more normal levels, it does not affect the body's natural process to form a clot when needed. Anagrelide is taken in capsule form by mouth. It can be taken with or without food. The capsule strength and the number of times a day you need to take anagrelide will depend on your platelet count, your response to treatment and how well you tolerate the drug.

Your doctor will keep track of your response to anagrelide and adjust your dose as needed to maintain your platelet count at the desired level. Side effects are generally mild to moderate and may decrease with continued therapy. The most commonly reported side effects include headaches, fast or forceful heart beat (palpitations), diarrhoea, weakness, fluid retention, nausea, dizziness, abdominal pain and shortness of breath. 

You should report any side effects you are experiencing to your doctor as many of them can be treated to reduce any discomfort to you. You need to contact your doctor immediately if you experience the following symptoms: shortness of breath or difficulty breathing, swollen ankles, fast or irregular heartbeat, and / or chest pain.

You should not stop taking this or any other medication for polycythaemia vera unless instructed by your doctor. Stopping these medications suddenly can be harmful.

Radioactive phosphorus ( 32P)

Radioactive phosphorus (32P) is a radioisotope which may be used for long-lasting control of blood counts in older people. One or two doses of 32P are usually given by injection into a vein in the hand or arm, in the nuclear medicine department of the hospital. This substance is taken up and concentrated in bone marrow where it suppresses the overactive bone marrow and helps to control blood counts.

In addition to the treatments described above, your doctor will advise you on ways to stay healthy and reduce any 'life-style' factors that might increase your risk of thrombosis. For example you may be advised to stop smoking, and/or take a series of steps to maintain a healthy weight range and blood pressure.

Prognosis

A prognosis is an estimate of the likely course of a disease. It provides some guide regarding the chances of curing the disease or controlling it for a given time.

The natural course of polycythaemia vera can vary considerably between individuals. In many patients, with treatment, the disease remains stable for long periods of time, often many years. In around 10% of all cases, polycythaemia vera transforms over time into another type of myeloproliferative neoplasm called myelofibrosis, and less commonly, in up to 3% of cases into acute myeloid leukaemia.

In some people, polycythaemia progresses over time despite treatment. The spleen may become increasingly enlarged. Anaemia and thrombocytopenia (low numbers of circulating platelets) is common as the bone marrow is no longer able to produce adequate numbers of red cells or platelets. In addition, abnormal immature blood cells, known as blast cells may start to appear in the blood.

Treatment during this time is supportive and involves making every effort to improve the patient's quality of life, by relieving any symptoms they might have and by preventing and treating any complications that arise from their disease or its treatment. This may involve blood transfusions if required, pain relief and careful myelosuppression.

In selected cases, surgical removal of the spleen, or low dose radiation to the spleen may be required to relieve symptoms.

Your doctor is the best person to give you an accurate prognosis regarding your disease as he or she has all the necessary information to make this assessment.