The Relationship of Blood Product Ratio to Mortality: Survival Benefit or Survival Bias?

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Abstract
Background: Recent studies show an apparent survival advantage associated with the administration of higher cumulative ratios of fresh frozen plasma (FFP) to packed red blood cells (PRBC). It remains unclear how temporal factors and survival bias may influence these results. The objective of this study was to evaluate the temporal relationship between blood product ratios and mortality in massively transfused trauma patients. Methods: Patients requiring massive transfusion (>10 units of PRBC within 24 hours of admission) between 2005 and 2007 were identified (n = 134). In-hospital mortality was compared between patients receiving high (>1:2) versus low (<1:2) FFP:PRBC ratios with a regression model, using the FFP:PRBC ratio as a fixed value at 24 hours (method I) and as a time-varying covariate (method II). Results: The FFP:PRBC ratio for all patients was low early and increased over time. Sixty-eight percent of total blood products were given and 54% of deaths occurred during the first 6 hours. Using method I, patients receiving a high FFP:PRBC ratio (mean, 1:1.3) by 24 hours had a 63% lower risk of death (RR, 0.37; 95% CI, 0.22–0.64) compared with those receiving a low ratio (mean, 1:3.7). However, this association was no longer statistically significant (RR, 0.84; 95% CI, 0.47–1.50) when the timing of component product transfusion was taken into account (method II). Conclusions: Similar to previous studies, an association between higher FFP:PRBC ratios at 24 hours and improved survival was observed. However, after adjustment for survival bias in the analysis, the association was no longer statistically significant. Prospective trials are necessary to evaluate whether hemostatic resuscitation is clinically beneficial.