Venesection vs Active Monitoring in Secondary Polycythaemia
Incidence of polycythaemia is 10-50/100,000 per year.
Patients with polycythaemia have a higher thrombotic rate than baseline population.
There is robust RCT evidence that venesection reduces thrombotic risk in patients with primary polycythaemia but this only makes up 5% of patients with polycythaemia.
There is evidence that venesection of patients with secondary polycythaemia can produce a transient improvement in symptoms and there is data from small physiological studies suggesting improvements in pulmonary blood flow in patients with polycythaemia secondary to COPD.
There is very little (if any) evidence suggesting that reducing haematocrit in patients with secondary polycythaemia improves meaningful clinical outcomes.
There is known harm from venesection however including syncopal events and accidental arterial / nerve injury. There is a significant time / day unit / clinic burden on the NHS of venesection of patients with secondary polycythaemia.
We have performed an international survey suggesting approx 35% of clinicians never venesect patients with polycythaemia and approx 55% venesect in the context of certain clinical features such as prior unprovoked VTE, ATE and symptoms including visual disturbance and headaches.
Of those who would venesect in certain situations most 2/3 would use a Hct threshold of 0.6 and a target of 0.55 but a significant minority (25%) would use a threshold of 0.55 and a target of 0.52.
Most of the 123 clinicians answering the survey would be happy to enrol patients into an RCT.
We have performed a retrospective multicentre audit with 260 patients with secondary / idiopathic polycythaemia followed up for 5 years. 60% are not venesected, of the 40% that are, number of venesections over 5 years ranges from 1 to 25. Venesection thresholds and targets vary widely.
Importantly we see that the mean Hct reduces to the normal range after ~1 year regardless of whether venesection is performed or not.
We also see that the 5 year thrombotic rate in these patients is 11%. This is unaffected by whether the patients are venesected or not and is unaffected by whether their Hct returned to normal or not.
The only baseline variable that predicted thrombosis was prior unprovoked VTE.
Maybury et al Brit J Haem 2025
We propose an RCT of patients with secondary polycythaemia of venesection vs simple follow up.
Patients: Patients with newly diagnosed secondary (+/- idiopathic?) polycythaemia (JAK2 Neg, Normal / High EPO [NM RCM scan for discussion) who haven’t undergone venesection but have received lifestyle advice and are undergoing optimisation of related underlying medical conditions.
Intervention: Venesection with a Hct threshold of 0.6 (or 0.55 if prior unprovoked VTE or polycythaemia related symptoms) and a target of 0.55 (or 0.52 if unprovoked VTE or symptoms)
Comparison: 3 monthly follow up with active monitoring of FBC
Outcome:
Primary Outcome: Thrombosis (VTE / ATE) at 5 years
Secondary outcomes: Survival at 5 years, Patient quality of life, Healthcare utilisation related to polycythaemia