Polycythaemia vera is a myeloproliferative disorder associated with overproduction of all blood cells and, as a result, an increased risk of thromboembolism. With an incidence of 1 to 2 cases per 100,000 population annually, polycythaemia vera is a rare syndromic disease.
What is polycythaemia vera?
Polycythaemia vera is a chronic myeloproliferative disorder in which there is increased synthesis of all blood cells, particularly erythrocytes, in the bone marrow. As a result of this progressive and irreversible overproduction, there is an increase in hematocrit (cellular blood components) and blood viscosity (viscosity), leading to microcirculatory disorders and an increased risk of thromboembolic events. In addition, two clinical stages are differentiated in polycythaemia vera. The first stage is characterized by increased erythrocyte synthesis as well as erythrocytosis (increased red blood cell count) and may be completely asymptomatic. The progressive late phase is characterized by secondary marrow fibrosis with extramedullary hematopoiesis and splenomegaly. Similarly, polycythaemia vera can develop into myelodysplasia, in which hematopoiesis is increasingly taken over by mutant stem cells, or acute myeloid leukemia.
Causes
The exact etiology of polycythemia vera has not yet been determined and is probably based on a mutational transformation of stem cells that has not yet been completely recorded and that can profile into different specific cell types. Thus, in about 95 percent of affected individuals, a so-called JAK2V617F point mutation could be detected, which leads to an exchange of the amino acid valine with phenylalanine and thus to an increased division rate of the specifically affected cells. In 2 to 3 percent, a functionally comparable JAK2 mutation in exon 12 (amino acid coding DNA segment) was also observed. Because these mutations also occur in other myeloproliferative syndromes such as essential thrombocythemia and primary myelofibrosis, possible triggering factors such as noxious agents (including benzene), ionizing radiation, and the involvement of another, as yet unknown, gene mutation are also being discussed.
Symptoms, complaints, and signs
Polycythaemia vera is characterized by excessive production of red blood cells (erythrocytes). As a result, the blood thickens and its flow properties deteriorate. The associated circulatory problems can cause a variety of symptoms. Polycythaemia vera often begins insidiously, so that many patients initially show few symptoms. Circulatory disorders in the hands and feet are among the more common symptoms. Likewise, a blue discoloration (cyanosis) of the lips occurs due to a lack of oxygen supply. The face, arms and legs, on the other hand, show reddening of the skin. Especially after contact with water, many patients with polycythaemia vera complain of itching. This is also referred to as aquagenic pruritus. The so-called erythromelalgia is also a characteristic symptom of the malignant blood disease. It is characterized by painful and sudden overheating and redness of the feet and/or hands. The increased amount of erythrocytes may further lead to dizziness, nosebleeds, visual disturbances or ringing in the ears. Due to the altered flow properties of the blood, there is also an increased risk of vascular occlusion due to blood clots (thrombosis) or embolisms. Reduced blood flow to the coronary arteries, on the other hand, leads to a feeling of tightness in the chest (angina pectoris) and additionally increases the risk of a heart attack.
Diagnosis and course
Initial suspicion of polycythaemia vera is often based on elevated erythrocyte, hematocrit, or hemoglobin levels in a blood test. In addition, in many cases of the disease there is an increased leukocyte and platelet count with a simultaneously decreased erythropoietin level (EPO level). In the advanced stage of the disease, the suspicion can be substantiated by splenomegaly. The diagnosis is additionally confirmed by the detection of the JAK2(V617F) point mutation.Differentially, polycythaemia vera (primary erythrocytosis) must be distinguished from secondary erythrocytoses such as stress erythrocytosis, smoker’s erythrocytosis, and erythrocytoses due to hypoxia or EPO-producing tumors in the liver or kidney, which are characterized by elevated EPO levels. With early diagnosis and controlled therapy, the disease has a good prognosis with approximately normal life expectancy despite its chronic progressive course. If left untreated, polycythaemia vera is associated with a substantially increased risk of thromboembolic events (including stroke, thrombosis, and myocardial infarction).
Complications
In this disease, patients primarily suffer from a markedly increased volume of blood. This also results in reddening of the skin, which can be unpleasant, especially on the face, and thus considerably reduces the patient’s quality of life. The blood itself is viscous, so that clotting is also usually disturbed. The brain is also incorrectly supplied with blood, which can lead to personality disorders or mood swings. In many cases, those affected suffer from severe headaches or dizziness. Due to the disease, the risk of stroke or heart attack increases enormously, so that the life expectancy of the patient can also be significantly reduced. In most cases, polycythaemia vera is treated with the help of medication. Patients often have to take the medication permanently in order to minimize the risk of thrombosis. No particular complications or side effects occur. Possibly, the life expectancy of the affected person is also reduced due to polycythaemia vera. Furthermore, a healthy lifestyle also has a very positive effect on the course of this disease.
When should one go to the doctor?
Disturbances and irregularities in blood flow should be presented to a doctor. If there is palpitations, dizziness, an internal warmth or an unusual sensation of cold in some areas of the body, the affected person needs help. If there are perceptual disturbances, a tingling sensation in the limbs, numbness or hypersensitivity, a physician should be consulted. Changes in skin appearance, itching or redness should be presented to a physician. If open wounds appear, sterile wound care is required. If the affected person cannot provide this sufficiently, a doctor should be consulted. Otherwise, germs can enter the organism and trigger further illnesses or sepsis. This could result in a life-threatening condition. Bleeding from the nose or gums, a feeling of tightness in the organism and general functional disorders must be examined and treated. In case of impaired vision as well as ringing in the ears, a clarification of the complaints should be carried out. If an acute health-threatening situation occurs, an ambulance service should be alerted. In case of disturbances of consciousness or loss of consciousness, an emergency doctor is needed. A strong decrease of the internal forces, a collapse as well as a sudden overheating are alarm signals of the body. In polycythaemia vera, a blood clot may form. In severe cases, a stroke or restriction of cardiac activity occurs. Without emergency medical care for the affected person, premature death is imminent.
Treatment and therapy
To date, the only causal or curative treatment for polycythaemia vera is stem cell transplantation. Because such an intervention is associated with a high risk of sequelae and increased mortality, it is generally considered only in the very advanced stages of the disease. In contrast, palliative therapy measures aimed at reducing the risk of thromboembolic events, alleviating symptoms and preventing complications are at the forefront of the treatment of polycythaemia vera. For this purpose, phlebotomy is usually initiated to reduce the hematocrit level, which ensures a rapid and effective reduction of blood volume. Initially, phlebotomy is performed at two- to three-day intervals, depending on the specific hematocrit level present, with the interval between treatments increasing as treatment progresses. To minimize the risk of thrombosis and to treat the microcirculatory disorders, a thrombosis aggregation inhibitor (low-dose ASA) is used simultaneously.If short intervals between the required phlebotomy sessions or high platelet counts can be observed on a permanent basis, a drug reduction of the cell count value is additionally aimed at within the framework of a cytoreductive therapy by means of active agents such as Hydroxurea or cytokines, which inhibit the synthesis of all blood cells in the bone marrow. In some cases in which a targeted reduction in platelet count is indicated, anagrelide, which has a suppressive effect on platelet maturation, can be applied to treat polycythaemia vera.
Prevention
Because polycythaemia vera is most likely due to a mutation of stem cells whose trigger factors (precipitating factors) have not yet been clearly elucidated, the disease cannot be prevented. However, weight reduction, regular exercise, avoidance of long periods of sitting, and consistent therapy for cardiovascular disease minimize the increased risk of thromboembolism in polycythaemia.
Follow-up
In most cases of polycythaemia vera, patients have very few and also limited measures of follow-up care available to them. Here, first and foremost, a rapid and, above all, a very early diagnosis is important to prevent other complications or further discomfort. Therefore, affected persons should see a doctor at the first symptoms or signs of the disease in order to prevent further complications or complaints. As a rule, self-healing cannot occur. The treatment itself involves a minor surgical procedure. Afterwards, affected persons should rest and take it easy. They should refrain from exertion and from physical or stressful activities in order not to put unnecessary strain on the body. Medication should also be checked regularly and adjusted by a doctor. If there are any uncertainties or questions about the medication, a doctor should always be contacted first. Regular controls by a doctor are also very important in order to control the blood count permanently. Whether polycythaemia vera leads to a reduced life expectancy of those affected cannot be universally predicted in this context.
What you can do yourself
Self-help options are generally not available to the person affected by polycythaemia vera. In any case, the patient is dependent on treatment by a physician, which involves a transplantation of stem cells. In some cases, despite treatment, the patient dies. In general, the patient with polycythaemia vera must take care of his body and not expose himself to unnecessary stress. Sporting activities should also be avoided, as they strain the body. Stressful situations should also be avoided. In case of itching, the affected area should not be scratched to avoid a rash. Due to the increased risk of heart attack, regular checkups with a doctor are very useful to avoid a heart attack. Examinations for tumors in the kidneys or liver are also useful, as these can also be favored by polycythaemia vera. In some cases, contact with other people affected by the disease is useful, as this can lead to an exchange of information, which can be helpful for everyday life and make life easier. In most cases, the patient’s life expectancy is reduced by polycythaemia vera.
