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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 polycythaemia, i.e. polycythaemia vera PV Polycythaemia Vera (Pv) is a chronic myeloproliferative disease. Usually pancytosis is present in the blood picture in PV, i.e. there is (neutrophil-predominant) leucocytosis and thrombocytosis in addition to the erythrocytosis.

PV
Secondary polycythaemias
- Hypoxia-induced
  - Staying at high altitudes (mountains)
  - Congenital heart disease
  - Chronic pulmonary disease
  - Others (e.g. rigid thorax, marked obesity, heavy smoking)
- Causes apparently associated with increased erythropoietin (EPO) production
  - Renal diseases (cysts, tumours)
  - Some neoplastic diseases (hepatoma, haemangioblastoma, renal carcinoma, phaeochromocytoma, myomas)
Familial erythrocytosis
Abnormal haemoglobins (such as Hb Helsinki, Hb Link�ping)
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, pancytosis as well as general symptoms (tiredness, icthing, nausea). Additionally, bleeding and thrombotic events occur. In the diagnostic phase, however, PV may primarily appear as 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
The WHO criteria (2016) for PV provides an alternative to investigating the increased red blood cell mass: blood haemoglobin > 165 g/l / haematocrit 0.49 (men), haemoglobin > 160 g/l / haematocrit 0.48 (women).
Red cell mass	Increased	Increased	Normal
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
Spontaneous growth in stem cell culture	Often	No	No
JAK2 mutation	>95% of cases	No	No

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.