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. 2025 Sep;120(9):866-873.
doi: 10.1111/vox.70072. Epub 2025 Aug 7.

Onsite vasovagal reactions with and without loss of consciousness are distinct outcomes with different risk factors

Christina Mikkelsen  1   2 , Betina Samuelsen Sørensen  3 , Bitten Aagaard  3 , Sys Hasslund  4 , Mie Topholm Bruun  5 , Rune Larsen  6 , Louise Ørnskov Drechsler  4 , Maria Didriksen  1 , Michael Schwinn  1 , Joseph Dowsett  1 ; DBDS Genomic Consortium; Erik Sørensen  1 , Christian Erikstrup  4   7 , Ole B Pedersen  6   8 , Niels Grarup  2 , Kari Stefansson  9   10 , Morten Bagge Hansen  1   8 , Torben Hansen  2 , Sisse Rye Ostrowski  1   8
Collaborators, Affiliations

Onsite vasovagal reactions with and without loss of consciousness are distinct outcomes with different risk factors

Christina Mikkelsen et al. Vox Sang. 2025 Sep.

Abstract

Background and objectives: Vasovagal reactions (VVRs) are some of the most common adverse reactions (ARs) in blood donors. While researchers have tried to develop precise risk prediction tools, these studies have all combined onsite and offsite reactions as well as reactions with and without the loss of consciousness. This study aimed to investigate potential differences in risk phenotypes in onsite VVRs, here defined as syncope and near-fainting.

Materials and methods: We included 40,543 participants from the Danish Blood Donor Study (136 syncope and 1453 near-fainting cases). Data on lifestyle and health were available from questionnaires. Data on donation type, time of day and ARs were available from the blood bank it-system. The risk of VVRs was assessed in a logistic mixed-effects model which included 345,751 donations. For genotyped participants (N = 21,102), polygenic scores were calculated for syncope, anxiety, neuroticism and cardiometabolic disease.

Results: Risk of both types of VVR was found to increase during warmer season and apheresis donation and reduce by donating late in the day. In addition, less donation experience and lower height increased the risk for near-fainting. In contrast, no donor-specific characteristics appeared to mediate the risk of syncope. Genetic predisposition of various traits had no effect on the risk of onsite VVRs.

Conclusion: This study indicates that onsite syncope and near-fainting are distinct conditions with different risk profiles. Our findings emphasize the importance of a more detailed analysis of VVRs, suggesting that the common practice of combining VVR subtypes may reduce the accuracy of risk prediction.

Keywords: blood donation; donor protection; haemovigilance; vasovagal reactions.

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Conflict of interest statement

K.S. is an employee at Amgen Inc. N.G. is employed at Novo Nordisk. All other authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Post hoc analysis of phenotypes with pairwise comparison of case and control groups. Post hoc analyses for age, blood volume and height (a–c) were performed using Tukey HSD. Dunn's test was used for donations before/after inclusion, pain at donation and the mental component score (d–g). For sex, smoking and donation type (h–j), groups were compared 1:1 with chi‐squared test. Significance levels are defined as *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001; ****p ≤ 0.0001. ns, non‐significant.
See this image and copyright information in PMC

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