Polycythaemia vera
Polycythaemia vera is a rare blood cancer that causes your bone marrow to produce too many red blood cells, making your blood thicker and increasing the risk of serious complications like blood clots, heart attack, and stroke.
Table of contents
- What is polycythaemia vera?
- Causes and genetic factors
- Who is affected by polycythaemia vera?
- Symptoms
- Complications and risks
- How is polycythaemia vera diagnosed?
- Treatment
- Living with polycythaemia vera
- Outlook and prognosis
polycythemia vera, primary polycythemia, polycythemia rubra vera, erythema, Osler-Vaquez disease, erythremia, Vaquez disease, Osler-Vaquez disease, polycythemia rubra vera, PV, PCV
What is polycythaemia vera?
Polycythaemia vera is a type of blood cancer that begins in the bone marrow, the soft center inside your bones where new blood cells grow[1][2]. The disease causes your bone marrow to make too many red blood cells, which are the cells that carry oxygen throughout your body[1].
When you have too many red blood cells, your blood becomes thicker and flows more slowly through your blood vessels[1][2]. This thick blood can cause serious problems, such as blood clots that may lead to heart attacks or strokes[1][6].
Polycythaemia vera is classified as a myeloproliferative neoplasm, which is a group of diseases where the bone marrow produces too many blood cells[2][3]. Although it primarily affects red blood cells, it can also cause your body to produce too many white blood cells and platelets[2][3].
This disease develops very slowly and often isn’t diagnosed until after the age of 60[2]. Many people don’t notice any symptoms at first, and the condition is often discovered during a routine blood test done for another reason[1][7].
Causes and genetic factors
The exact reason why polycythaemia vera develops is not known, but researchers have discovered important genetic changes that cause the disease[5]. The most significant finding is that approximately 95% to 98% of people with polycythaemia vera have a mutation in a gene called JAK2[3][5][7].
The most common mutation is called JAK2 V617F, which is found in about 95% of patients[7]. In other cases, mutations occur in exon 12 of the JAK2 gene[7]. This genetic mutation causes problems with how your blood-forming cells respond to growth signals, leading them to multiply uncontrollably[3][5].
The mutation in the JAK2 gene is not inherited from parents in most cases[6]. Instead, it develops during a person’s lifetime for unknown reasons[2][3]. However, in rare cases, polycythaemia vera risk may run in families[6].
Some risk factors that may increase the chance of developing polycythaemia vera include exposure to intense radiation or toxic substances[5], though these connections are still being studied.
Who is affected by polycythaemia vera?
Polycythaemia vera is a rare disease. It affects about 50 per 100,000 people in the United States[2], with rates between 0.6 to 1.6 per million people annually[3]. The disease is less common in Japan compared to the United States or Europe[3].
The disease can affect people of all ethnic groups and both sexes, though men are slightly more likely to develop it than women[3][6]. While polycythaemia vera can occur at any age, it is most common in people over the age of 60, with the median age of diagnosis being 60 years[2][3][5].
Symptoms
Many people with polycythaemia vera don’t notice any problems at first[1][7]. The condition is often discovered during a routine complete blood count test that reveals an increase in red blood cells[5].
When symptoms do appear, they can include a wide range of problems. Common symptoms include headaches, dizziness, tiredness, and blurred vision[1][6]. Some people experience ringing in their ears, called tinnitus[2][4].
One distinctive symptom is severe itching, especially after taking a warm bath or shower[1][6][7]. This itching, called pruritus, is present in 40% to 55% of patients with polycythaemia vera[7]. The itching may be caused by abnormal release of histamine or prostaglandin production[7].
Some people develop a condition called erythromelalgia, which causes a burning pain in the hands or feet, usually accompanied by redness or bluish coloring of the skin[6][7]. This happens because of increased platelet counts or platelet “stickiness” that causes tiny blood clots to form in blood vessels of the hands and feet[7].
Other symptoms can include shortness of breath, trouble breathing when lying down, numbness or tingling in the hands or feet, a feeling of fullness after eating, bloating or pain in the left upper stomach area, unusual bleeding such as nosebleeds or bleeding gums, painful joint swelling, and bone pain[1][4]. Some people also experience night sweats, unexpected weight loss, and weakness[4][6].
The red face that looks like sunburn or blushing is another visible sign of the disease[6]. You may also feel pressure or fullness below your ribs on your left side, which might mean the disease has enlarged your spleen, an organ that helps filter your blood[6].
Complications and risks
The most serious and urgent risk from polycythaemia vera is the tendency for blood clotting[2]. The extra red blood cells make your blood thicker and slow down circulation, which increases the likelihood of blood clots forming[2].
A blood clot that travels to your heart or brain can cause a heart attack or stroke[2][6]. A clot that gets stuck in your lungs, called a pulmonary embolism, can cause pulmonary hypertension, leading to heart failure[2]. A blood clot that blocks a vein, known as venous thromboembolism, can cause tissue death and chronic venous insufficiency[2].
A particularly serious complication is when a clot blocks the main blood vessel leading to your liver, called hepatic vein thrombosis. This can cause blood to back up into the liver, a condition called Budd-Chiari syndrome, which can lead to jaundice and liver failure[2].
Over time, polycythaemia vera can lead to several secondary conditions. High red blood cell turnover produces high levels of uric acid in your body[2]. This can cause kidney stones when uric acid builds up in your kidneys, and gout, a painful form of arthritis, when uric acid builds up in your joints[2][4].
Extra red blood cells also lead to more stomach acid, which can cause stomach ulcers[2]. The extra red blood cells trigger an immune response, causing your body to release histamine, and your stomach responds by creating more acid[2].
The thickened blood slows circulation, meaning your blood carries less oxygen to your body’s tissues and organs than they need[2]. The extra work also affects your spleen, which is responsible for filtering your blood and clearing out old blood cells. This can cause the spleen to become swollen and sore, a condition called splenomegaly[2].
In rare cases, polycythaemia vera can progress to more serious blood cancers. Approximately 15% of patients may develop other conditions over time[5]. Some people may develop myelofibrosis, a disorder where the bone marrow is replaced by fibrous scar tissue[4]. In rare cases, the disease can progress to acute myelogenous leukemia[4].
How is polycythaemia vera diagnosed?
Diagnosis of polycythaemia vera begins with your healthcare professional taking a medical history and performing a physical exam[9]. Often, the initial diagnosis occurs when a routine complete blood count reveals an increase in red blood cells[5].
Several blood tests are used to confirm the diagnosis. If you have polycythaemia vera, blood tests might show more red blood cells than usual and sometimes an increase in platelets or white blood cells[9]. Tests will also measure a higher portion of red blood cells that make up total blood volume, called hematocrit measurement, and a higher level of hemoglobin, the iron-rich protein in red blood cells that carries oxygen[9].
Additional diagnostic tests may include a complete blood count with differential, comprehensive metabolic panel, and erythropoietin level test[4]. An analysis of red blood cells may indicate a low erythropoietin level, which is a hormone involved in red blood cell production[4][5].
The most important diagnostic test is genetic testing for the JAK2 gene mutation[4][9]. Approximately 95% to 98% of polycythaemia vera patients test positive for a JAK2 gene mutation[5][7].
Your healthcare professional might also suggest getting a sample of your bone marrow through a bone marrow aspiration or biopsy[9]. A bone marrow biopsy involves taking a sample of the spongy tissue in bone marrow, while a bone marrow aspiration removes a sample of the liquid portion of your marrow[9]. These procedures are often done at the same time[9]. A bone marrow biopsy may reveal an excess of precursors to red blood platelets, red blood cells, and white blood cells[5].
Other tests that may be performed include vitamin B12 level testing, oxygen saturation of the blood, and various tests to check for effects on other organs[4].
Treatment
There is no cure for polycythaemia vera, but treatment aims to lower your risk of complications and ease your symptoms[2][9]. Most people manage symptoms well for many years with proper medical care[2].
The most common treatment is having blood withdrawn regularly using a needle in a vein, a procedure called phlebotomy[4][9]. This is the same procedure used for donating blood. During phlebotomy, about one unit of blood (roughly one pint or half a liter) is removed each week until the number of red blood cells drops[4]. The procedure takes anywhere from 10 to 30 minutes[14]. This treatment lowers your blood volume and reduces the number of excess blood cells[9]. How often you need to have blood withdrawn depends on how severe your condition is[9].
Medications are also used to manage polycythaemia vera. A low dose of aspirin can protect you from blood clots[6]. Your doctor will tell you whether that’s a good option and the right amount you need[6]. Aspirin may also help with headaches, vision problems, and burning sensations in the hands and feet[6].
Other medicines that may be used include hydroxyurea to reduce the number of red blood cells made by the bone marrow, particularly when the numbers of other blood cell types are also high[4][9]. Interferons may be prescribed to lower blood counts, especially in pregnancy[4][9]. Interferon injections may also help combat itching, weight loss, and drenching sweats[6].
Ruxolitinib (also known by the brand name Jakafi) may be prescribed to reduce the number of red blood cells and reduce an enlarged spleen, particularly when hydroxyurea and other treatments have failed[4][9]. A drug called anagrelide (Agrylin) can help prevent clots[6].
A newer treatment called rusfertide has shown promise in clinical trials. This drug blocks the production of iron-rich blood cells and has been shown to substantially reduce the need for phlebotomy treatments[14]. In one trial, participants who received rusfertide had their need for phlebotomy drop from an average of nine procedures per year to less than one per year[14]. However, rusfertide is not yet approved by regulatory authorities and is currently only available to those participating in clinical trials[14].
For managing specific symptoms, antihistamines or light therapy can help control itching[4][9]. A type of antidepressant called a selective-serotonin reuptake inhibitor, such as fluoxetine (Prozac) or paroxetine (Paxil), may also help with itching[6][9]. Medications like allopurinol (Zyloprim) can prevent gout flare-ups[6].
Living with polycythaemia vera
While your lifestyle hasn’t caused polycythaemia vera, there are simple things you can do which may make a difference to how you feel, both mentally and physically[15].
Staying hydrated is particularly important when you have thicker blood[15]. Healthcare guidelines recommend drinking 6 to 8 glasses of water or other low-fat, low-sugar drinks every day, including tea and coffee[15]. Ask your hospital team to advise you how much fluid you should be aiming to drink each day[15].
If you smoke, it’s important to stop or at least cut down, as smoking increases your risk of blood clots[15]. Since polycythaemia vera also increases this risk, stopping smoking is particularly important[15]. Support services are available to help you quit[15].
Staying as active as you can is important[15]. You can tackle fatigue with an exercise program, beginning gradually[6]. As you build up, your strength and energy level should improve, and your blood will circulate better, which can help prevent clots[6]. Special exercises for your legs and ankles can help prevent deep vein thrombosis[6].
To help manage itching at home, lower the temperature of your shower or bath, especially in winter[6]. Pat yourself dry to avoid irritating your skin, and use lotion to moisturize[6]. Don’t scratch, as it can damage your skin and increase your infection risk[6].
Regular follow-up care is essential. People with polycythaemia vera regularly visit their doctor to check their hematocrit level[14]. If it’s too high, they then undergo therapeutic phlebotomy[14]. Your healthcare team will advise you on how often you need monitoring and treatment[9].
Outlook and prognosis
Most people with polycythaemia vera enjoy longevity if they receive regular monitoring and treatment[5]. The disease develops slowly, and most people do not have symptoms related to the disease at the time of diagnosis[4].
With proper medical care, most people manage symptoms well for many years[2]. The condition is often diagnosed before severe symptoms occur[4]. This type of cancer usually isn’t fatal by itself, with the main risks coming from complications of blood clotting or from the small chance that it would progress to more aggressive types of blood cancer[2].
However, in some cases, prolonged survival can be challenged by the development of other conditions[5]. Possible complications include acute myelogenous leukemia, bleeding from the stomach or other parts of the intestinal tract, gout, heart failure, myelofibrosis, and blood clots[4].
Regular medical care and following your treatment plan are essential for managing the disease and reducing the risk of complications. With ongoing advances in treatment, including new medications being tested in clinical trials, the outlook for people with polycythaemia vera continues to improve[14].
