Polycythaemia: Prevention, Diagnosis and When to See a Doctor

Polycythaemia means having too many red blood cells, making the blood thicker and increasing the risk of clots. It can be a primary bone marrow disease or a secondary consequence of factors such as smoking, sleep apnoea or testosterone use. Our editorial team explains the different types, how they are diagnosed and when to seek medical advice.

What polycythaemia is

Red blood cells carry oxygen from the lungs to the tissues. Their concentration is measured as haemoglobin and haematocrit, the percentage of blood volume occupied by red cells. When these values rise above normal ranges, the blood becomes more viscous, flows less easily and is more likely to clot.

The term erythrocytosis is often used interchangeably with polycythaemia, although strictly speaking polycythaemia can refer to an increase in all blood cell types. In clinical practice, doctors focus on haematocrit, with persistently raised values prompting investigation.

There are three broad categories. Relative polycythaemia occurs when plasma volume falls, for example in dehydration, so red cells appear concentrated without an actual increase in their number. Secondary polycythaemia results from increased erythropoietin (EPO) production or external stimulation. Primary polycythaemia, most commonly polycythaemia vera, is a bone marrow disorder.

Distinguishing between these types is essential, because their treatment and outlook differ substantially.

Causes: primary and secondary

Polycythaemia vera is a myeloproliferative neoplasm, a chronic blood cancer in which the bone marrow produces too many red cells, often along with white cells and platelets. More than 95 per cent of patients carry a mutation in the JAK2 gene, a discovery reported in 2005 (James et al.) that transformed diagnosis.

Secondary causes are more common in practice. Chronic low oxygen levels from smoking, lung disease, obstructive sleep apnoea or living at high altitude stimulate EPO release. Some kidney and liver tumours can also produce EPO.

Testosterone is a well-recognised cause. It stimulates red cell production directly and via EPO and iron metabolism. In testosterone replacement therapy, erythrocytosis is one of the most frequent adverse effects (Ohlander et al., 2018). The risk is greater with injectable forms and with supraphysiological doses used outside medical practice.

Symptoms and complications

Many people with polycythaemia have no symptoms, and the condition is discovered on a routine blood test. When symptoms occur, they often reflect sluggish blood flow: headaches, dizziness, tinnitus, blurred vision, fatigue and a red or flushed complexion.

A characteristic symptom of polycythaemia vera is itching after a warm bath or shower, known as aquagenic pruritus. Burning pain and redness in the hands or feet (erythromelalgia) and an enlarged spleen, causing a feeling of fullness under the left ribs, may also occur.

The most serious complications are blood clots, both arterial and venous. These include stroke, heart attack, deep vein thrombosis and pulmonary embolism, as well as clots in unusual sites such as abdominal veins. The CYTO-PV trial (Marchioli et al., 2013) showed that keeping haematocrit below 45 per cent in polycythaemia vera significantly reduced cardiovascular deaths and major thrombosis.

Diagnosis

Diagnosis begins with a full blood count. Because haematocrit can vary with hydration, an abnormal result is usually repeated. A persistently raised haematocrit, typically above about 52 per cent in men or 48 per cent in women, prompts further investigation, although laboratories and guidelines use slightly different thresholds.

The British Society for Haematology guideline (McMullin et al., 2019) outlines a stepwise approach: confirming the result, reviewing history including smoking, alcohol and medicines, checking for JAK2 mutation, measuring serum EPO and assessing for secondary causes.

• Full blood count with haematocrit and haemoglobin.
• JAK2 V617F mutation test.
• Serum erythropoietin level.
• Ferritin and iron studies.
• Kidney and liver function, and oxygen saturation.
• Abdominal ultrasound or sleep study when indicated.

In men receiving testosterone therapy, the Endocrine Society guideline (Bhasin et al., 2018) recommends checking haematocrit at baseline, at three to six months and then annually, and reconsidering therapy if it exceeds 54 per cent.

Prevention and when to see a doctor

Not all polycythaemia can be prevented. Polycythaemia vera arises from an acquired mutation and is not caused by lifestyle. Secondary forms, however, can often be reduced or avoided.

Stopping smoking is one of the most effective measures. Diagnosing and treating sleep apnoea, often suspected in people who snore loudly and feel sleepy during the day, can normalise red cell counts. Staying well hydrated avoids relative polycythaemia.

For people on prescribed testosterone, regular blood tests and dose adjustments by the prescriber are key. Non-medical use of anabolic steroids or EPO carries a substantially higher risk, because nobody monitors haematocrit and doses are often much higher than therapeutic.

Seek urgent medical help, by calling 999, if you experience symptoms of stroke such as facial drooping, arm weakness or speech problems, chest pain, sudden breathlessness, or a painful swollen leg. See your GP if you have persistent headaches, itching after bathing, unexplained fatigue or a raised haematocrit on a blood test.

Editorial conclusions

Polycythaemia means an excess of red blood cells, which thickens the blood and raises the risk of clots, stroke and heart attack.

It can be relative, secondary to factors such as smoking, sleep apnoea or testosterone, or primary in the form of polycythaemia vera.

Regular blood tests, addressing modifiable causes and prompt medical attention for warning symptoms are the cornerstones of prevention and early diagnosis.

Our editorial team also recommends articles on haematocrit and testosterone therapy, how sleep apnoea affects hormones, and blood tests every active person should consider.

References

1. 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.
2. Marchioli R, Finazzi G, Specchia G, et al. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med. 2013;368(1):22–33.
3. James C, Ugo V, Le Couédic JP, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005;434(7037):1144–1148.
4. Ohlander SJ, Varghese B, Pastuszak AW. Erythrocytosis following testosterone therapy. Sex Med Rev. 2018;6(1):77–85.
5. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715–1744.
6. https://steroidstorejapan.com/