29th May 2023

Polycythaemia

Polycythaemia is defined as Hb >185 in males and >165 in women. In practice, haematocrit (HCT) is a more reliable indicator of polycythaemia (HCT >0.52 in males, >0.48 in females)

Primary polycythaemia

This includes rare congenital forms but is mostly synonymous with an acquired malignant condition known as polycythaemia vera. This is due to a somatic mutation in a hematopoietic stem cell. In over 95% of cases, this is a mutation in the JAK2 gene.

Because it is the stem cell that is mutated, there can be an increase in all three myeloid cell lines (RBC, platelets, and granulocytes). The erythropoietin (EPO) level will be low due to negative feedback.

The incidence is 2 cases per 100,000 people per year. The median age at presentation is 65-75 years.

Features:

• Splenomegaly
• Arterial and venous thrombosis including Budd-Chiari syndrome
• Pruritus, particularly after a bath or shower
• Erythromelalgia – itching or burning in extremities (see image)
• Haemorrhage
• Gout
• Constitutional symptoms

Photo showing characteristic changes during an episode of erythromelalgia.
Image Source: Wikimedia Commons (2017). Erythromelalgia in left hand, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Erythromelalgia_in_left_hand.jpg (Accessed on: 10 January 2023).

Confirmation of the diagnosis requires JAK2 positive mutation with a persistently elevated haematocrit >0.52 in males and >0.48 in females.

Without treatment, life expectancy is around 18 months – death is most commonly due to stroke or MI. Median survival is 14 years with treatment. There is a 5-15% risk of transformation to myelofibrosis over 10 years and the risk of progression to AML is ~2% at 10 years and 8% at 20 years.

Management:

1. Reduce cardiovascular risk factors
2. Low dose aspirin for all patients
3. Venesection to reduce the HCT to below 0.45 target
4. Cytoreductive therapy (usually hydroxycarbamide or interferon first line) for high-risk patients (>65 years or history of thrombosis)

Secondary polycythaemia

Secondary polycythaemia is a much more common cause of a raised haematocrit than polycythaemia vera. These conditions will show a raised EPO level. They are summarised in the table below:

Management is generally aimed at identifying and treating the underlying cause.

Relative polycythaemia

This is caused by decreased plasma volume causing a proportional increase in HCT but without an increase in absolute red cell mass. It corrects on normalisation of intravascular plasma volume.