Polycythaemia rubra vera (PRV) is a myeloproliferative disorder, which means the bone marrow makes too many blood cells. In PRV, sometimes just called polycythaemia vera (PV), there is an abnormally high number of red blood cells in your blood.
This is because the myeloid stem cells in your bone marrow have started to multiply out of control. As these stem cells can develop into either red blood cells, platelets or white blood cells, if you have PRV, you may also have an abnormally high number of platelets and white blood cells.
An abnormally high number of red blood cells is called erythrocytosis. An abnormally high number of platelets is called thrombocytosis. An abnormally high number of white blood cells is called leukocytosis.
Because of the extra number of blood cells circulating if you have PRV, your blood becomes more viscous. This means that it is thicker or more sludgy than normal.
This causes your blood to flow more slowly, and also causes an increased risk of a blood clot (thrombosis) forming.
Over 19 in 20 people with PRV have an abnormality (called a mutation) in a protein called the JAK2 protein. The JAK2 protein normally helps to regulate and control the production of blood cells.
So, it is thought that the abnormal JAK2 protein is involved in the stem cells starting to multiply out of control in people with PRV.
The cause of the JAK2 protein problem may be as a result of some damage to the bone marrow. For example, damage due to a viral infection or due to background radiation.
However, more research is needed to find the exact cause.
PRV is one of a group of diseases called myeloproliferative disorders. In all myeloproliferative disorders, there is excessive production of blood cells in the bone marrow for whatever reason.
In 2008 the World Health Organization changed the way it classifies these blood conditions. From 2008 PRV has been classified as a myeloproliferative neoplasm – a type of blood cancer.
Polycythemia Primary Causes
In primary polycythemia, inherent or acquired problems with red blood cell production lead to polycythemia.
Two main conditions that belong to this category are polycythemia vera (PV or polycythemia rubra vera [PRV]) and primary familial and congenital polycythemia (PFCP).
Polycythemia vera (PV) is related to a genetic mutation in the JAK2 gene, which is thought to increase the sensitivity of bone marrow cells to Epo, resulting in increased red blood cell production.
Levels of other types of blood cells (white blood cells and platelets) are also often increased in this condition.
Primary familial and congenital polycythemia (PFCP) is a condition related to a mutation in the EPOR gene and causes increased production of red blood cells in response to Epo.
Polycythemia Secondary Causes
Contrary to primary polycythemia in which overproduction of red blood cell results from increased sensitivity or responsiveness to Epo (often with lower than normal levels of Epo), in secondary polycythemia, more red cells are produced because of high levels of circulating Epo.
The main reasons for higher than normal Epo are chronic hypoxia (poor blood oxygen levels over the long-term), poor oxygen delivery due to abnormal red blood cell structure, and tumors releasing inappropriately high amounts of Epo.
Some of the common conditions that can result in elevated erythropoietin due to chronic hypoxia or poor oxygen supply include:
- chronic obstructive pulmonary disease (COPD, emphysema, chronic bronchitis),
- pulmonary hypertension,
- hypoventilation syndrome,
- congestive heart failure,
- obstructive sleep apnea,
- poor blood flow to the kidneys, and
- living in high altitudes.
2,3-BPG deficiency is a condition in which the hemoglobin molecule in the red blood cells has an abnormal structure.
In this condition, hemoglobin has a higher affinity to hold on to oxygen and is less likely to release it to the tissues.
This results in more red blood cells being produced in response to what the tissues in the body perceive as an inadequate oxygen level. The outcome is more circulating red blood cells.
Certain tumors have a tendency to secrete inappropriately high amounts of Epo, leading to polycythemia. The common Epo-releasing tumors are:
- liver cancer (hepatocellular carcinoma),
- kidney cancer (renal cell carcinoma),
- adrenal adenoma or adenocarcinoma, and
- uterine cancer
There also are more benign conditions that may cause increase Epo secretion, such as kidney cysts and kidney obstruction.
Chronic carbon monoxide exposure can also lead to polycythemia. Hemoglobin naturally has a higher affinity for carbon monoxide than for oxygen. Therefore, when carbon monoxide molecules attach to hemoglobin, polycythemia (increased red cell and hemoglobin production) may occur in order to compensate for the poor oxygen delivery by the existing hemoglobin molecules. A similar scenario can also occur with carbon dioxide in long-termcigarette smoking.
Polycythemia in newborns (neonatal polycythemia) is often caused by transfer of maternal blood from the placenta or blood transfusions.
Prolonged poor oxygen delivery to the fetus (intrauterine hypoxia) due to insufficiency of the placenta can also lead to neonatal polycythemia.
How common is polycythaemia rubra vera?
PRV is not very common. It is thought that about 2 in 100,000 people develop PRV each year. PRV can affect people of any age. However, most people are diagnosed at around the age of 60.
What are the symptoms and possible complications?
PRV can cause a number of different symptoms or complications (described below). However, not everyone with PRV will have all of these.
Some people have only mild symptoms, whilst others may develop one or more complications. Treatment (see below) can help to reduce your chance of developing symptoms and complications.
Symptoms because of sludgy blood flow
The sludgy blood flow means that oxygen (that is carried bound to haemoglobin in your red blood cells) cannot get to the tissues of your body as easily. This can lead to various symptoms, including:
- Ringing in your ears (tinnitus)
- Blurring of your vision
- Chest pain or pain in your calf muscles when walking
What is the treatment for polycythaemia rubra vera?
There is no cure for PRV. The aim of treatment is to reduce the chance of you developing symptoms or complications due to PRV.
However, as mentioned above, not everyone may develop symptoms or complications. Sometimes it can be difficult for doctors to predict who is likely to develop complications and so what treatment is best.
This is the main treatment for PRV. Essentially, this removes the extra red blood cells and so helps to make your blood thinner (less viscous) so that it circulates better.
Venesection is done by removing blood, usually from a vein in your arm, using a needle and syringe – a bit like when someone donates blood.
Regular venesection is usually needed if you have PRV, until your red blood cell numbers have reduced and your blood thickness is satisfactory.
Medicines to help slow the production of red blood cells
In many people with PRV, a medicine may also be suggested to help to slow down the production of red blood cells. Some medicines also slow down the production of platelets.
The decision about starting such treatment with medicines, and what medicine to use, depends on various things. These include:
- Your age
- Your red blood cell count
- How well venesection is working and how well you are managing with this
- What your platelet levels are
Whether you have already had problems with either blood clots (thromboses) or bleeding.
Various drugs may be considered and they are discussed below.
They have different advantages and disadvantages. Your blood specialist (haematologist) will be able to discuss with you the medicine that may be best in your situation. Some medicines can have effects on your fertility and also on a developing baby.
Ask your doctor if you have PRV and are considering trying for a baby. This includes both men and women.