Dear Editor,
Thank you for sending the letter to the editor of Preußel and Offergeld [1] which we have read with interest. The authors criticize the methodological issues of our study about safety of plasmapheresis in donors with low IgG levels [2].
First, we want to point out that we did not extract data from an intensified plasmapheresis study but from our individualized plasmapheresis study. Preußel and Offergeld [1] raise the following concerns about our study:
The authors criticize the follow-up period and the high dropout rate of the donors. High dropout rates are observed in prospective plasmapheresis studies as it was reported in the SIPLA study [3]. Most of the dropouts in those studies are due to socioeconomical reasons [3, 4]. Our intensified plasmapheresis study was designed for a participation time up to 12 years [5]. Thus, it is easily understandable that high dropout rates during this long study period were expected. To compensate dropouts, our aim was to include 30,000 donors to ensure sufficient statistical power. As of July 13th 2022, 21,742 donors were included in the study protocol. Unfortunately, many donors gave no feedback reasons for withdrawal from the study. However, cancellation “due to discomfort possibly related to low IgG level” as mentioned by the authors is speculative. According to the study protocol, donors are followed up for 8 months after the last donation.
The authors assume a conflict of interest of donors reporting adverse event (AE) and their wish to donate. As we were aware of the possibility of underreporting of AEs, donors were actively screened for AEs including infections: the donor questionnaire included questions about AEs and infections during or after the last donation and in the case of an affirmative answer a physician recorded and evaluated the side effect. Furthermore, study donors were closely monitored about side effects by physicians at the physical examination at every 15th plasma donation and at the annual examination. This procedure is standard of care, and we want to point out that our study protocol with reporting of AEs was approved by 8 German ethics committees and continuously monitored by a data safety committee. Our reported low values of infections are due to the fact that plasma donors are a positively selected population subgroup fulfilling the eligibility criteria of healthy donors. Therefore, lower incidence values than in the common population are expected in this special subgroup.
It is right that the donors of the control arm were not stratified. However, in the present study, we retrospectively differentiated the participating control-arm donors with respect to initial IgG levels.
It is also clear that the individualized arm donors have higher initial IgG levels because the donors were allowed to choose between the individual and control group. However, the initial IgG levels had no impact on the focus of the present evaluation.
In conclusion, retrieving data from a large data base of a multicenter study, we showed that donor safety was not compromised in donors with low IgG levels provided that an efficient IgG management was conducted in all study groups. There is no evidenced-based data justifying a permanent donor deferral of donors with ≥3 IgG measurements below the threshold of 6.0 g/L as stated in current German hemotherapy guidelines [6]. Reentry of currently unjustified deferred donors with ≥3 IgG measurements below the threshold will allow an increase of the plasma donor pool, thereby improving European self-sufficiency with plasma-derived medicinal products.
Conflict of Interest Statement
The authors are employees at Octapharma Plasma GmbH.
Funding Sources
The study was funded by Octapharma Plasma GmbH.
Author Contributions
R.M. drafted the manuscript. All the authors critically reviewed, revised, and approved the final version of the manuscript.
Funding Statement
The study was funded by Octapharma Plasma GmbH.
References
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