Polycythaemia Blood Tests: FBC, Haematocrit & JAK2 Mutation

What Is Polycythaemia?

Polycythaemia (also spelt polycythemia) refers to an abnormally high concentration of red blood cells in the blood. This makes the blood thicker (more viscous) and increases the risk of dangerous blood clots, including deep vein thrombosis, pulmonary embolism, stroke, and heart attack. It is typically detected incidentally on a routine full blood count (FBC) when the haemoglobin or haematocrit is found to be elevated.

Polycythaemia can be relative (apparent) — caused by reduced plasma volume, often due to dehydration — or absolute (true), where there is a genuine increase in red cell mass. Absolute polycythaemia is further divided into primary and secondary types.

Key Blood Test Findings

The following FBC parameters are relevant in polycythaemia:

• Haemoglobin (Hb): elevated above the normal range. In men, this is typically above 165 g/L; in women, above 160 g/L.
• Haematocrit (Hct/PCV): the proportion of blood volume occupied by red cells. A haematocrit above 0.52 in men or 0.48 in women is the key threshold that triggers further investigation. The BSH (British Society for Haematology) uses these cut-offs in its diagnostic pathway.
• Red blood cell count: typically elevated, often above 6.0 × 10¹²/L in men.

If the haematocrit is persistently elevated on repeat testing (after excluding dehydration), further investigations are warranted.

Primary Polycythaemia: Polycythaemia Vera

Polycythaemia vera (PV) is a myeloproliferative neoplasm — a type of slow-growing blood cancer in which the bone marrow produces too many red blood cells. It is caused by an acquired genetic mutation, most commonly the JAK2 V617F mutation, which is found in approximately 95% of PV patients. A smaller proportion carry the JAK2 exon 12 mutation.

The JAK2 mutation causes the JAK-STAT signalling pathway to be constitutively active, meaning the bone marrow produces red cells even without the normal erythropoietin stimulus. PV is diagnosed using the WHO 2022 criteria, which include:

• Major criterion 1: Hb above 165 g/L in men or 160 g/L in women, OR haematocrit above 0.49 in men or 0.48 in women.
• Major criterion 2: Bone marrow biopsy showing hypercellularity with trilineage growth (panmyelosis).
• Major criterion 3: Presence of JAK2 V617F or JAK2 exon 12 mutation.
• Minor criterion: Serum erythropoietin (EPO) level below the normal reference range.

Diagnosis requires either all three major criteria or the first two major criteria plus the minor criterion.

Secondary Polycythaemia

Secondary polycythaemia occurs when the body produces excess red blood cells in response to an external stimulus, usually hypoxia (low oxygen levels) or inappropriate erythropoietin production. Common causes include:

• Smoking — the most common cause of secondary polycythaemia in the UK. Carbon monoxide binds to haemoglobin, reducing oxygen delivery and triggering compensatory red cell production.
• Chronic lung disease — COPD, pulmonary fibrosis, and other conditions that impair oxygenation.
• Obstructive sleep apnoea — intermittent nocturnal hypoxia stimulates erythropoietin production.
• Living at high altitude — less relevant in the UK but important for patients who have recently relocated.
• Renal tumours or cysts — some kidney tumours produce erythropoietin inappropriately.
• Testosterone replacement therapy (TRT) — exogenous testosterone stimulates red cell production and can cause polycythaemia as a side effect.

In secondary polycythaemia, the JAK2 mutation is negative and serum erythropoietin is typically normal or elevated (in contrast to PV, where EPO is suppressed).

Referral Criteria

The BSH recommends urgent haematology referral for patients with a persistently raised haematocrit (above 0.52 in men or 0.48 in women) after secondary causes have been excluded. The referral pathway typically includes:

• Repeat FBC to confirm the finding is persistent (not due to dehydration).
• JAK2 V617F mutation testing.
• Serum erythropoietin level.
• Ferritin (often low in PV due to increased red cell production consuming iron stores).
• Renal and liver function tests.
• Oxygen saturation assessment (pulse oximetry or arterial blood gas).

Treatment and Monitoring

Treatment depends on the underlying cause:

• Secondary polycythaemia: address the underlying cause (smoking cessation, CPAP for sleep apnoea, adjusting TRT dose). Venesection (therapeutic blood removal) may be used if the haematocrit remains dangerously high.
• Polycythaemia vera: venesection to maintain haematocrit below 0.45 (both men and women). Low-dose aspirin (75 mg daily) to reduce thrombotic risk. Cytoreductive therapy (usually hydroxycarbamide) may be added for high-risk patients (age over 60, history of thrombosis, or very high platelet count).

Patients with PV require lifelong monitoring with regular FBC tests, typically every 3–6 months when stable, to track haematocrit, haemoglobin, platelet count, and white cell count. Annual review should include liver function, renal function, and ferritin.

Getting Tested at Home

If a routine blood test has shown a raised haemoglobin or haematocrit, or if you are being monitored for polycythaemia, a mobile phlebotomist can take your follow-up blood samples at home. This is particularly convenient for patients who require regular FBC monitoring and want to avoid repeated hospital visits. Explore our home blood test services to arrange a convenient appointment.