Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

Abstract

SummaryBackgroundLimits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries.MethodsIn this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants.Findings45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p<0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p<0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p<0·0001 for each) than those observed in the standard frequency groups.InterpretationOver 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency.FundingNHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation.

Elevated risk for iron depletion in high‐school age blood donors

“…In women of reproductive age, alterations to cognitive function have been associated with NAID . The recently published INTERVAL study, a randomized trial that assigned 45,000 UK donors to different levels of donation frequency, found no difference in cognitive function by donation frequency, but the study was powered for other outcomes and did not include subjects 16 or 17 years‐old . Any clinical impact from donation‐associated iron depletion may be subtle and challenging to detect, and this issue would benefit from further scientific inquiry.…”

Blood, sweat, and tears: Red Blood Cell‐Omics study objectives, design, and recruitment activities

“…The Interval study 28,29 is a randomized clinical trial of primary white (>91%) blood donors. RBC-Omics, in contrast, is racially and ethnically heterogeneous.…”

Changes in minimum hemoglobin and interdonation interval: impact on donor hemoglobin and donation frequency

“…Hb deferral rates also increase with frequent donation . The UK INTERVAL study, where donors were randomized to donate at a specific donation interval, clearly demonstrated the link between interdonation intervals, ferritin levels, and Hb deferrals …”

“…Minimum interdonation intervals provide time for donors to replenish lost iron and, ideally, return to their pre‐donation Hb level. However, studies performed in Canada and other countries demonstrate that many donors with Hb levels above the cutoff are iron deficient, and that a short interdonation interval (or high frequency of donation) is a major risk factor for iron deficiency . In the Hemoglobin and Iron Recovery Study (HEIRS), donors without iron supplementation required considerably more than 56 days to return to baseline ferritin and Hb levels …”

“…Until 2016, Canadian Blood Services (CBS) followed Canadian Standards Association standards for blood and blood components, which specify a minimum Hb level of 125 g/L and a minimum interdonation interval of 56 days (8 weeks) for both males and females . Based on normal physiological differences in Hb and iron stores in females and males, and Canadian and international data on risk factors for donor iron deficiency, CBS increased the minimum Hb cutoff from 125 g/L to 130 g/L for male donors and the minimum interdonation interval from 56 days (8 weeks) to 84 days (12 weeks) for female donors in 2016–17 . We proactively invested in programs to increase new donor recruitment and encourage lapsed donors to return to donate in order to ensure the adequacy of the blood supply.…”