Researchers in Denmark recently published a paper in Vox Sanguinis that sought, “to characterize the risk of phenotypes and genotypes of onsite vasovagal reactions (VVRs) alone, [classified] as syncope or near-fainting reactions, to investigate whether vasovagal reaction risk stratification based on subtype could be meaningful in donor vigilance.” They examined, “lifestyle characteristics as well as mental and physical health, which in the future would allow [for the development of] a risk stratification tool that can be applied before the donor enters the donation facility.”
Individuals participating in the study included whole blood, plasmapheresis, and platelet apheresis donors who completed a health questionnaire upon enrolling. The authors noted that, “[p]henotype data were available for 40,543 donors. A total of 1,453 experienced at least one near-fainting episode and 136 at least one syncopal reaction. Across all three groups (no adverse reactions (ARs), syncope, and near-fainting), there was a difference in sex distribution, age at inclusion, number of donations before and after inclusion, height and blood volume (BV), donation type at inclusion, smoking status, pain at donation, and mental component score (MCS).” Understanding vasovagal reaction risk in these populations is crucial for improving donor safety.
The study found that, “[n]ear-fainting cases were younger than in the other two groups (no reaction and syncope) and had lower height and BV). [Additionally,] near-fainting cases had fewer donations before inclusion compared to controls. Near-fainting cases also reported higher pain levels during donation than controls and had lower MCS compared to both syncope cases and controls…The near-fainting group also included a higher proportion of female donors. [There were no] significant differences in red blood cell count, white blood cell count, or h[e]matocrit across the groups.” Recognizing vasovagal reaction risk can guide the creation of more effective donor management practices.
The researchers also explained that, “[f]or both VVR types, the risk was increased by apheresis donation and warmer season, whereas donation after lunch appeared to be protective. For near-fainting, the risk was reduced by donation experience and increasing height. Older age also showed a tendency towards a significant protective effect.” The paper noted that, “[n]o syncope-specific risk factors were identified. No significant interaction between sex and age was found for any of the VVR types. Modelling was performed first with height and then later with BV. Further understanding of vasovagal reaction risk factors, including environmental influences, can improve risk assessments.
Increasing BV significantly reduced the risk of near-fainting (odds ratio [OR] 0.67, 95 percent CI: 0.52–0.86, p=0.002) but not syncope (OR 0.54, 95 percent CI: 0.18–1.62, p=0.274). Platelet counts or h[e]matocrit had no effect on either near-fainting or syncope risk. [The authors found] no association between genetic predisposition and the risk of near-fainting or syncope, both in the univariate and fully adjusted logistic models.”
The researchers concluded that, “we found important differences in risk phenotypes for onsite VVRs with and without loss of consciousness (LOC). Whereas near-fainting risk is partly mediated by donation experience and height/BV, syncope risks appear to be entirely mediated through donation-specific characteristics. We furthermore found that genetic predisposition of syncope, anxiety, neuroticism, or coronary artery disease does not appear to have any effect on the risk of onsite near-fainting. Recognizing the vasovagal reaction risk associated with these differences can enhance donor safety protocols. The results highlight that current VVR research is significantly limited by the practice of combining syncope and near-fainting into a single entity, rendering it ineffective for predicting syncope.”
The researchers acknowledged that limitations of the study included, “[t]he relatively small number of cases, especially for syncope, was the main limitation as well as the reason for not sex-stratifying the analysis. For the same reason, we were not able to investigate the impact of genetic predisposition on the risk of syncope or potential differences in risk factors across different donation types. In addition, a larger sample is needed to investigate all four types of VVR: onsite and offsite reactions with and without LOC. Another important limitation is that all participants had at least one donation prior to inclusion, as first-time donor status is a known important risk factor.”
Citation: Mikkelsen, C., Sørensen, B.S., Aagaard, B., et al. “Onsite vasovagal reactions with and without loss of consciousness are distinct outcomes with different risk factors.” Vox Sanguins. 2025.