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Old PRBCs linked to increased mortality across 16 studies
Figure 3. Forest plots for nosocomial infection analysis as a function of PRBC mean age. Nosocomial infection odds ratios were calcu- lated for each study using logistic regression with mean PRBC age transfused as the inde- pendent variable. Age, sex and PRBC volume were entered into the model as covariates. Odds ratios were then combined using random effects models. OR: odds ratio; CI: confidence interval.
changed during the recruitment period (1980-2011), alter- ing the effects of PRBC age on adverse events. Notably, the association between PRBC age and mortality persisted after leukoreduction – one of the major changes in PRBC processing over the past 20 years. The mean volume of PRBC transfused in this study was approximately four units, signifying that the results likely have limited appli- cability to massive transfusion protocols where more than ten units can be transfused in one incident.
This pooled patient data analysis may have been affect- ed by confounding factors due to the use of observational studies, as patients were not randomly allocated to treat- ment groups. This pooled patient analysis incorporated three covariates – age, sex and PRBC volume, which have been demonstrated to be the most influential confounders over multiple studies.32,33 The assessment of a limited sub- set of observational studies introduced the risk of selection bias. This effect was less likely to affect the observed asso- ciation between PRBC age and mortality as it aligned with the results of existing meta-analyses.11 Furthermore, included studies were similar to excluded studies in terms of study size, recruitment dates and rates of positive mor- tality findings.
Pooled IPD analysis found an association between PRBC >30 days and increased risks of in-hospital mortali-
ty. This result was significant as 24.5% of all O negative PRBC units are transfused after 35-42 days of storage in Australia.34 These results align with the findings of in vitro studies and support the shortening of PRBC shelf life to 35 days, which has already occurred in some jurisdictions (The Netherlands, UK, Germany, China). Shortening PRBC shelf life should be approached with caution due to its implications for blood bank management, product wastage and PRBC access in remote locations. Ideally, these findings should be confirmed using extremes analy- ses of pooled patient data from recent large RCTs prior to implementing changes.
Acknowledgments
We would like to thank Professor Cartotto, Professor Edna, Professor Gajic, Professor Juffermans, Doctor Kadar, Professor Cooper, Professor Phelan, Doctor Sanders, Professor van de Watering, Doctor Voorhuis and Doctor Yap for providing access to their patient-level data.
Funding
Australian governments fund the Australian Red Cross Blood Service for the provision of blood, blood products and services to the Australian community. This project was partially funded by The Prince Charles Hospital Foundation.
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