In Focus
Bacterial risk remains even with bacterial culture or pathogen reduction
Moving beyond the expectation of zero risk
Blood components are unique biological products as they are not required to be sterile - not because they are inherently safe, but because historically we lacked technologies capable of ensuring sterility.
Over the last 20 years bacterial safety technologies have evolved, culminating in two widely deployed state-of-the-art technologies, large volume delayed sampling (LVDS) bacterial culture and amotosalen/UVA pathogen reduction. Recent hemovigilance data now records that transfusion-transmitted bacterial infection with platelet transfusions has fallen substantially, but it has not disappeared (Figure 1).
Figure 1. Rates of Transfusion Transmitted Bacterial Infection (TTBI) & Contamination with LVDS Culture or Pathogen Reduction
Before the introduction of effective interventions, reported rates of transfusion-transmitted bacterial sepsis were commonly around 10 cases per million components, and in some settings considerably higher. While data from hemovigilance systems must be interpreted cautiously because surveillance, case ascertainment and definitions differ substantially between countries, recent reports now inform residual risk assessments.
LVDS culture has reduced the risk dramatically, with hemovigilance data from several countries suggesting sepsis rates of 0.5–5.0 cases per million platelet components transfused.1,2 Near misses, caught as visually contaminated products at the bedside especially with Staphylococcus aureus, remain a problem and suggest considerably higher failure rates that may represent an underappreciated risk. Amotosalen/UVA pathogen reduction has produced lower rates of 0.0-1.0 per million, but near misses have also been recorded.3
Near-miss events should be regarded as system failures and not as successes of detection. When a contaminated component is identified before transfusion, we have been fortunate to intercept the event. We do not know how many similar events were not detected. Including near misses therefore provides a more realistic assessment of residual risk.
Where can bacterial safety systems fail?
Even with LVDS, culture samples only a fraction of the component and depends on organisms being present in the sampled volume and sufficiently metabolically active to grow during the culture period. Slow-growing organisms, low-level contamination and bacteria associated with surfaces or biofilms can therefore escape detection.
One potential mechanism is particularly relevant to Staphylococcus aureus. This organism has a strong capacity to adhere to plastic surfaces and form biofilms. If bacteria remain attached to the platelet storage bag rather than suspended in the component, sampling may fail to capture them. One possible approach would be to transfer the platelet product into a fresh bag before sampling, thereby potentially disrupting this reservoir. Although this hypothesis requires experimental confirmation, it illustrates an important limitation of culture-based strategies: what we sample may not necessarily represent the entire biological environment of the component.
Another concern is the deliberate release of components before culture results are fully mature. When products enter inventory while cultures are still incubating, some contaminated components may inevitably be transfused before a positive signal becomes available. This is an inherent trade-off between guaranteeing platelet availability and maximizing microbiological detection.
The clinical significance of organisms classified as slow-growing and “low pathogenicity” also deserves reconsideration. The risk associated with bacterial contamination depends not only on species, but on bacterial concentration, strain characteristics and, critically, the susceptibility of the recipient. There is therefore no truly acceptable level of bacterial contamination simply because an organism is considered unlikely to cause disease.1
Pathogen reduction: different technology, different failure modes
Pathogen reduction changes the paradigm. Instead of attempting to detect contamination, it seeks to neutralize pathogens before transfusion. However, it is not equivalent to sterilization, and breakthrough infections demonstrate that its efficacy also has limits.
Failures may occur when bacterial concentrations exceed the capacity of the treatment process or when organisms possess intrinsic resistance. Certain spore-forming organisms and other resistant viral pathogens can survive treatment, while rapidly proliferating organisms such as Klebsiella sp. may potentially overwhelm the system under high bacterial loads.
Post-manufacturing contamination represents another challenge. Loss of bag integrity or manufacturing defects can allow environmental organisms to enter a component after processing. Neither LVDS nor pathogen reduction can protect against contamination that occurs after manufacture. This reinforces the importance of maintaining the integrity of the entire manufacturing and distribution chain rather than focusing exclusively on the manufacturing step.
Moving beyond the expectation of zero risk
We have transfused millions of LVDS-cultured or pathogen-reduced platelet components worldwide, and breakthrough contaminations continue to occur. Understanding the mechanisms underlying these events is essential. Bacteria are remarkably adaptable, and they will challenge every safety barrier we develop. The most important message is that no current bacterial safety technology eliminates risk completely. LVDS culture and pathogen reduction have both transformed platelet safety, but each has characteristic failure modes. We should resist the temptation to label individual bacterial species as clinically irrelevant or to interpret every negative surveillance result as evidence of absence. Hemovigilance remains essential, but its limitations mean that laboratory, clinical and manufacturing data must be integrated to understand residual risk, and physicians should maintain vigilance for the risk of contaminated platelets.
References
1. Chugh, V., S. Secret, K. Davison, et al. (2026). Bacterial screening of platelet donations in England, 2014-2023. Vox Sang 121(7): 999-1009. 2. Garcia-Otalora, M. A., C. McDonald, J. Bearne, et al. (2025). Platelet component safety in the era of new advancements in bacterial screening and pathogen reduction: A congress report of the 2024 ISBT Transfusion-Transmitted Infectious Diseases Working Party, Bacteria Subgroup. Vox Sang 120(8): 846-857. 3. Laperche, S., V. de la Taille, P. Gallian, et al. (2026). Pathogen-reduced platelet concentrates in France: Impact on the risk of transfusion-transmitted infections, 2017-2024. Vox Sang. 2026 May;121(5):581-586.
