Rombout‐Sestrienkova 2012.

Methods	Randomised clinical trial.
Participants	Country: Netherlands. Number randomised: 38. Post‐randomisation dropouts: 0 (0%). Revised sample size: 38. Mean age: 52 years. Number of women: 10 (26.3%). Symptomatic: not stated. Asymptomatic: not stated. Mean follow‐up period: 8 months. Target used for iron reduction: serum ferritin ≤ 50 μg/L. Inclusion criteria: Homozygosis for C282Y. Participants treatment naive. Aged 18 to 80 years. Weight ≥ 50 kg. Transferrin saturation > 50%. Serum ferritin > 450 mg/L. Haemoglobin concentration ≥ 7.5 mmol/L (120 g/L) in women and ≥ 8.0 mmol/L (128 g/L) in men. Exclusion criteria: Malignancy. Serious cardiac arrhythmias. Heart failure. Epilepsy.
Interventions	Participants were randomly assigned to 2 groups. Group 1: therapeutic erythrocytapheresis (n = 19). Further details: 350 mL to 800 mL of red blood cells once every 2 weeks. Group 2: phlebotomy (n = 19). Further details: 500 mL of whole blood once weekly. Treatment duration: variable depending upon the iron to be removed.
Outcomes	Mortality, adverse events, and health‐related quality of life.
Notes	We attempted to contact the corresponding author to obtain additional information on risk of bias and outcomes in June 2015. We did not receive any reply.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "patients were randomly assigned in a 1:1 ratio by an independent person working as quality assurance manager".
Allocation concealment (selection bias)	Low risk	Quote: "patients were randomly assigned in a 1:1 ratio by an independent person working as quality assurance manager".
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: "single‐blind".
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote: "single‐blind".
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: there were no post‐randomisation dropouts.
Selective reporting (reporting bias)	Low risk	Comment: all important outcomes were reported.
For‐profit bias	Low risk	Quote: "This work was performed with the support of the Sanquin Blood Bank grants 03‐006".
Other bias	Low risk	Comment: no other risk of bias.