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Erythrocytosis

A clonal haematological disease (polycythaemia vera, PV Polycythaemia Vera (Pv)) must be distinguished from secondary and relative erythrocytosis.

Erythrocytosis refers to an elevation of the total number of red cells in blood. In practical terms it can be defined by measuring either blood haemoglobin concentration, packed cell volume (haematocrit) or erythrocyte concentration.
- In women: haemoglobin > 155 g/l, haematocrit > 0.46, or erythrocytes > 5.2 × 10¹² /l
- In men: haemoglobin > 167 g/l, haematocrit > 0.50, or erythrocytes > 5.7 × 10¹² /l
Erythrocytosis may be relative (normal red cell mass but plasma volume decreased) or absolute (increased red cell mass). Absolute erythrocytosis may be primary (PV) or secondary.
Primary erythrocytosis, i.e. polycythaemia vera PV Polycythaemia Vera (Pv) is a chronic myeloproliferative disease. Secondary erythrocytosis is caused by excessive effect of EPO, which may be appropriate (lack of oxygen) or inappropriate (some neoplasms).

Primary erythrocytosis
- Polycythaemia vera (PV) Polycythaemia Vera (Pv)
- Rare EPO receptor mutations
Secondary erythrocytosis
- Hypoxia-induced appropriate EPO secretion
  - Staying at high altitudes (mountains)
  - Congenital heart disease
  - Chronic pulmonary disease
  - Kidney diseases (e.g. renal artery stenosis, cysts)
  - Others (e.g. marked obesity, heavy smoking)
- Inappropriate EPO secretion
  - Some neoplastic diseases (e.g. renal carcinoma, myomas, phaeochromocytoma, hemangioblastoma)
High oxygen affinity haemoglobinopathy (such as Hb Helsinki, Hb Linköping i.e. Hb Meilahti), other rare types of hereditary erythrocytosis
Medications (erythropoietin, androgens) that are increasingly used on non-medical indications. SGLT2 inhibitors also increase haemoglobin concentration fairly regularly.

Dehydration
Decreased plasma volume
Pseudopolycythaemia or stress polycythaemia (common among heavy smokers and obese persons)

The general practitioner evaluates the need for special investigations.
- Severe heart and lung diseases are often associated with polycythaemia and no special investigations are necessary.
  - The condition may be verified by measuring arterial oxygen partial pressure or oxygen saturation. Oxygen saturation should typically be less than 92%.
- PV patients often have mild splenomegaly and pancytosis as well as general symptoms. Additionally, bleeding and thrombotic events may occur. At the time of diagnosis PV is often an incidental finding with mild symptoms.
- Serum EPO concentration is low in PV.
- JAK2 mutation is found in > 95% of PV patients by using the relevant blood test (may be done in primary care).
Referral to a haematology clinic for treatment and follow-up decisions if polycythaemia vera is suspected on the basis of these examinations.
Table T1 lists the central differential diagnostic investigations.

Variable	Polycythaemia vera	Secondary erythrocytosis	Relative erythrocytosis
Leucocytosis	Often	No	No
Thrombocytosis	Often	No	No
Splenomegaly	Often	No	No
Causes of secondary polycythaemia excluded	Yes	No
Serum erythropoietin	Decreased	Increased or normal	Normal
JAK2 mutation	>95% of cases	No	No

Treatment

Treatment of PV is presented in a separate article Polycythaemia Vera (Pv).
In secondary erythrocytosis, treatment is directed against the underlying disease, and venesections are needed in special situations only (e.g. in central nervous system complications resulting from blood hyperviscosity).
In relative erythrocytosis, the possible dehydration is corrected, and the patient is supported in weight management and smoking cessation.

McMullin MF. Investigation and Management of Erythrocytosis. Curr Hematol Malig Rep 2016;11(5):342-7[PubMed]
Remes K. [Polycythaemia vera and other types of erythrocytosis]. In: Porkka K, Lassila R, Remes K, Savolainen E-R (eds.). [Diseases of the blood]. Duodecim Publishing Company Ltd 2015.