Characterizing red blood cell age exposure in massive transfusion therapy: the scalar age of blood index (SBI)

Abstract

Background: The mortality of trauma patients requiring massive transfusion to treat hemorrhagic shock approaches 17% at 24 hours and 26% at 30 days. The use of stored RBCs is limited to less than 42 days, so older RBCs are delivered first to rapidly bleeding trauma patients. Patients who receive a greater quantity of older RBCs may have a higher risk for mortality.

Methods and materials: Characterizing blood age exposure requires accounting for the age of each RBC unit and the quantity of transfused units. To address this challenge, a novel Scalar Age of Blood Index (SBI) that represents the relative distribution of RBCs received is introduced and applied to a secondary analysis of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) randomized controlled trial (NCT01545232, https://clinicaltrials.gov/ct2/show/NCT01545232). The effect of the SBI is assessed on the primary PROPPR outcome, 24-hour and 30-day mortality.

Results: The distributions of blood storage ages successfully maps to a parameter (SBI) that fully defines the blood age curve for each patient. SBI was a significant predictor of 24-hour and 30-day mortality in an adjusted model that had strong predictive ability (odds ratio, 1.15 [1.01-1.29], p = 0.029, C-statistic, 0.81; odds ratio, 1.14 [1.02-1.28], p = 0.019, C-statistic, 0.88, respectively).

Conclusion: SBI is a simple scalar metric of blood age that accounts for the relative distribution of RBCs among age categories. Transfusion of older RBCs is associated with 24-hour and 30-day mortality, after adjustment for total units and clinical covariates.

FIGURE 1.

Graph of the cumulative scalar blood age index (SBI) for 5 representative patients from the PROPPR trial. The table shows these patients’ exact PRBC units and their predicted 24 hour and 30 day mortality from the model. For example, patient 1 received a total of 9 PRBC units: 8 were aged 0–7 days old and 1 was 8–14 days old. The inlaid table maps SBI to age categories and predicted mortality at 24 hours and 30-days. Note: The predicted mortality is calculated at the sample mean or median for the following adjusters in the model: patient age, sex, race, mechanism of injury, Injury Severity Score, Revised Trauma Score, total PRBC units transfused in the first 24 hours after admission, and PROPPR trial treatment group.

FIGURE 2:

Distribution of SBI among all PROPPR trial patients. Patients transfused with predominately younger RBCs have increasingly more negative SBI values; whereas, patients transfused with predominately older RBCs have increasingly higher positive SBI values.

FIGURE 3:

The (unadjusted) proportion of 24-hour and 30-day patient mortality by SBI tertile and total PRBC units received. Mortality proportions are given on the y-axis by both SBI tertile on the first x-axis, and total PRBC blood unit category on the second x- axis. This 3-dimensional plot shows how mortality in PROPPR changes as a function of both SBI and total number of blood units received.