The major goal of the treatment is to prevent thrombotic complications and haemorrhages.
The amount of red blood cells is kept within the normal range (haematocrit < 0.45, haemoglobin < 145 g/l). This prevents cardiovascular deaths and thromboses.
Allopurinol is the primary drug for preventing gout symptoms and hyperuricaemic kidney lesions if urate levels are at the upper end of the normal range.
At the time of diagnosis, low-dose aspirin (100 mg/day) is given to reduce the risk of distal ischaemia and transcient ischaemic attacks.Low-Dose Aspirin for Patients with Polycythaemia Vera This dose is sufficient to reduce the risk of thrombosis in cerebral and coronary circulation.
Definition
PV is a chronic and progressive haematological disease caused by excessive blood cell production (precursor cells in the bone marrow and mature cells in the peripheral blood) by the hyperplastic bone marrow. Increased erythropoiesis, increased amount of red blood cells (erythrocytosis) and high haemoglobin levels are the prominent features.
Epidemiology
Approximately 2 new cases/100 000/year
Most common among middle-aged and elderly people: most patients are 50-70 years old.
Aetiology
Unknown
Diagnostic criteria
Modified WHO 2016 criteria
The diagnosis of polycythaemia vera requires meeting three major criteria, or the two first major criteria and the minor criterion.
Major criteria
Hb > 165 g/l (or hematocrit > 0.49) in men, Hb > 160 g/l (or hematocrit > 0.48) in women, or other evidence of increased red cell volume
Bone marrow biopsy: hypercellularity with trilineage growth (panmyelosis)
Bone marrow biopsy may not be required if Hb > 185 g/l in men or > 165 g/l in women and the major criterion 3 and the minor criterionare present. Bone marrow biopsy should generally be performed, however, before starting cytostatic pharmacotherapy. It is recommended to consult a haematologist at the time of diagnosis for defining treatment lines.
Differential diagnosis
Secondary erythrocytoses (serum EPO concentration often increased)
Often associated with cardiopulmonary diseases, heavy smoking
Abnormal O2 affinity haemoglobins, e.g. Hb Helsinki, Hb Linköping
In secondary polycythaemias the blood erythrocyte count is only mildly increased.
Relative erythrocytoses (red cell mass normal)
”Stress” polycythaemia
Dehydration
Other myeloproliferative conditions
Symptoms and signs
Redness of the skin
Hyperaemic conjunctivae
Mild splenomegaly
Hyperviscosity symptoms
Headache, dizziness
Numbness of the fingertips and erythromelalgia
Thrombotic symptoms
Itching
Gastrointestinal symptoms, often haemorrhages
Arthralgias
Neurological symptoms
In many cases, the PV diagnosis is set in patients with very mild or no symptoms after investigating for high haemoglobin concentration that originally was an incidental finding.
Laboratory findings
Erythrocytosis; also high haemoglobin and haematocrit unless iron deficiency is apparent. MCV and MCH values are often already decreased at the time of diagnosis.
Hypercellular bone marrow
Low serum erythropoietin concentration
Blood JAK2 gene mutation positive in over 95% of the patients.
See also diagnostic criteria (above).
Disease progression and prognosis
Progression is rather even. When PV is treated, the life expectancy of the patient is nowadays almost equal to the age-matched general population, i.e. 10-15 years. Life expectancy is influenced by age at diagnosis, occurrence of thrombosis and leukocytosis.
Provided that the patient avoids vascular catastrophes the disease may progress to myelofibrosis and sometimes eventually to acute leukaemia.
Complications
Thromboses and haemorrhages
Treatment and follow-up
The goal of treatment is to maintain the amount of red blood cells within the normal range (haematocrit < 0.45, haemoglobin < 145 g/l). When deciding on the treatment, an individual risk assessment which is based on the patient's age and thrombosis history is made. The course of treatment is planned by a haematologist, but the treatment may largely be carried out within primary care.
The lowering of red cell mass is started with venesections http://www.dynamed.com/condition/polycythemia-vera#PHLEBOTOMY (400-500 ml at a time) at an interval of a couple of weeks. If haemoglobin is > 200 g/l, 400 ml can be taken daily up to the maximum of 1 500-2 000 ml.
Venesections do not treat thrombocytosis, which may increase as a result of venesections.
If the annual number of venesections exceeds 6-8, pharmacological treatments should be considered. In younger patients this treatment should be postponed for as long as possible. If strong leucocytosis and thrombocytosis are present, cytoreductive therapy is often needed.
Cytostatic treatment
Given in primary care in collaboration with an experienced specialist.
With hydroxyurea the response is seen in one week; therapy requires intense follow-up in the beginning. Treatment is often long-lasting. Haemoglobin reduction starts to be seen in about one month. Hydroxyurea causes an increase in the size of red blood cells (macrocytosis).
32 P is given as a single dose. Effect begins in about 2 weeks (first in leucocytes, the in platelets and lastly in red cell counts) and lasts < 2 years. 32 P can be repeated a few times if the response to treatment was good.
Check local policies concerning reimbursement of interferon.
Allopurinol is used to prevent symptoms of gout and kidney damage, if plasma urate concentration is increased.
Aspirin may increase the risk of bleeding if the platelet count is high (> 1 000).
Follow-up
According to the therapy
Hydroxyurea: initially every 1-3 weeks, later every 3 months
32 P: first control after 1 month, thereafter every 2-4 months; in stable disease, every 4-12 months
Interferon alpha: in the same way as with hydroxyurea
References
McMullin MF, Harrison CN, Ali S et al. A guideline for the diagnosis and management of polycythaemia vera. A British Society for Haematology Guideline. Br J Haematol 2019;184(2):176-191.[PubMed]
Barbui T, Passamonti F, Accorsi P et al. Evidence- and consensus-based recommendations for phlebotomy in polycythemia vera. Leukemia 2018;32(9):2077-2081. [PubMed]