Commentary on Zhao et al., “Frequent platelet donations is associated with lymphopenia, and risk of infections: A nationwide cohort study”

The recent manuscript by Zhao and colleagues follows on the observation that very frequent and prolonged platelet donation on the Trima platform may result in CD4 lymphopenia in some donors. After a plateletpheresis donor was incidentally discovered to have a CD4 T-cell count below 200/μl, Gansner et al. performed a study of 60 donors, 20 from each of three cohorts: infrequent donors (1–2 donations in the last year), intermediate-frequency donors (3–19), and frequent donors (20–24). The investigators observed donation frequency-dependent lymphocytopenia in these three groups. Specifically, CD4 counts below 200/μl were observed in 0/20, 2/20 (10%), and 6/20 (30%) of the three groups, respectively. Similarly, low CD8 counts were observed in 0/20, 4/40, and 11/20. Despite the significant lymphocyte reduction, no donor reported health issues on a questionnaire. The measured collection efficiency demonstrated that most lymphocytes are returned to the donor but about 15–20% of mononuclear cells (MNCs) traveling through the apheresis machine are caught in the leukoreduction system (LRS) chamber. The authors posited that the LRS chamber, which captures on average 1.9 × 10 MNCs per collection, may be contributing to the observed progressive lymphopenia. The authors followed up with another study to compare the impact of frequent donation on an alternative platform. Of 30 participants all of whom had 20–24 apheresis platelet collections on the Amicus platform during the prior 12 months, none had CD4 counts below the 200/μl cutoff, although one donor had CD4 counts between 200 and 300 cells/μl. One additional donor had a CD8 count below the lower limit of normal but a normal CD4 count. In a third study, two subjects were noted with persistent CD4 counts below 200/μl, despite ceasing donation for over a year, although neither donor manifested evidence of immunosuppression—neither had an opportunistic infection or malignancy associated with low CD4 counts. Confronted with apparently platform-based lymphopenia in the most frequently donating subjects, the authors wrestled with the observation that despite frequent donors having statistically significantly lower lymphocyte counts, no adverse clinical impact was obvious in the finite number of donors they were able to query. Recognizing the challenge of collecting clinical data by survey, and the insensitivity of passive health data reporting collection by blood centers, the authors reached out to collection centers in countries with both national data sets on blood donors and countrywide healthcare outcomes data sets. This brought us to the Scandinavian Donations and Transfusion (SCANDAT) program in Sweden, which has access to decades of data on blood donors as well as many years of patient outcomes. Dr. Kaufman was connected with Gustaf Edgren via collaborators at the National Institutes of Health (NIH) who recognized the power of “big data” to potentially detect even modest increases in infection rates, at least those severe enough to result in hospitalization, among a subset of the population. Because apheresis platelet collections in Sweden are largely on the Trima platform, the investigators compared infection rates among frequent plateletpheresis donors with frequent plasmapheresis donors whose collections do not have an LRS chamber. The median annual donation rate in this cohort was about 8, similar to the donor frequency at many US centers. This comparison helps avoid the “If it's not one thing, it's another” — Rosanne Rosannadanna Received: 8 March 2021 Accepted: 8 March 2021