The effect of plasma donation frequency on total serum protein, immunoglobulin G and donor safety: A non‐inferiority randomized controlled trial

Background and Objectives The safety of varying plasma donation frequencies remains unclear. This non‐inferiority randomized controlled trial investigated the effect of plasma donation frequency on total serum protein (TSP), immunoglobulin G (IgG) concentrations, additional biomarkers, adverse events (AEs) and psychological distress. Materials and Methods In this trial, 120 male donors were randomized into three groups: high‐frequency plasma donors (HFPDs, three times every 2 weeks), regular‐frequency plasma donors (RFPDs, once every 2 weeks) and a control group (whole blood donation every 3 months). Blood samples were collected biweekly from baseline until the last donation in Week 16 and 4 weeks after the last donation. Results HFPDs completed median (range) 21.5 (1–24), RFPDs 8 (1–8) and controls 2 (1–2) donations. HFPDs had lower concentrations of TSP and IgG compared to controls, with a mean difference (95% confidence interval [CI]) of −5.5 g/L (−7.4, −3.6) and −2.8 g/L (−3.8, −1.8), respectively. Within‐group analysis revealed significant reductions, which increased with the frequency of donations, in TSP, IgG, IgG subclasses, immunoglobulin M (IgM), immunoglobulin A (IgA), ferritin and haemoglobin. Many of the biomarkers required more than 4 weeks to return to baseline levels. Only mild AEs were reported, and plasma donation frequency had no effect on psychological distress. Conclusion High‐ and regular‐frequency plasmapheresis substantially reduces concentrations of TSP, IgG and other biomarkers, with greater reductions at higher donation frequencies. Further research is needed to assess the long‐term health implications of frequent plasma donation.