Assistant Professor University of Wisconsin Madison, Wisconsin, United States
Background/Case Studies: It has been asserted that acute, that large-volume transfusions are less likely to provoke red cell alloimmunization than the same dose given over a long period. Presumptive explanations include loss of native immune cells, transfusion-associated immunomodulation, or the inflammatory stress of bleeding. We hypothesized that there would be a biphasic risk of red cell alloimmunization following a large-volume transfusion episode, rising linearly as total red cell dose increased up to transfusion of approximately half a blood volume, after which they would not increase.
Study
Design/Methods: We performed a retrospective cohort study of all recorded inpatients undergoing surgery or invasive procedures at a single academic hospital. Patients were included if they had an antibody screen followed by transfusion of at least one unit of red blood cells, and then had at least one more antibody screen completed in the 11-180 days after the transfusion. We excluded patients with a new positive screen less than 11 days after the transfusion. We only analyzed the transfusion episode with the largest dose of red cells in a 24-hour period for each patient. A priori, we assumed that there would be an inflection point around 5 units of RBCs. We also assumed that estimated blood volume, age, and comorbidity burden would be significant confounders. We fit a piecewise Cox Proportional Hazards model of time to new alloimmunization, with a knot at a dose above 5 units of red cells, and censored at 180 days or death.
Results/Findings: There were 6,400 unique participants between September 4, 2009 and December 28, 2022, 6376 with complete data. The average age was 54 ± 22 years, and 44% were female. The median RBC dose during the encounter was 2 units (interquartile range 1-3) with a maximum of 165 units. 194 participants (3.0%) had a new alloimmunization in the 11 to 180 days after exposure. The rate of alloimmunization increased with RBC dose up to 6 units, after which the risk leveled at approximately 4% (Figure 1). Among the 516 participants under 40 kg, there were only 4 (0.8%) alloimmunizations, 2 after 1 unit and 2 after 6 units. In the piecewise Cox Proportional Hazards model, alloimmunization-free survival was significantly associated with total red cell dose < 5 units (hazard ratio [HR] 1.1, 95% confidence interval [CI] 1.0 – 2.2), total red cell dose ≥5 units (joint HR 0.99, 95% CI 0.79 – 1.0, p < 0.046) and estimated blood volume in liters (HR 1.2, 95% CI 1.1 – 1.3). No other covariates were significant. Conclusions: We found that alloimmunization-free survival after an acute transfusion episode was directly related to the total dose of red cells only up to 5 units, after which it is constant. These data support the hypothesis that high-intensity transfusions have a blunted risk of red cell alloimmunization compared to equivalent chronic exposures.
Importance of research: Our results demonstrate that rapid exposure to a large number of red blood cell units has a dose-dependent risk of RBC alloimmunization only up to approximately 5 units, after which it is relatively constant. This suggests that ongoing transfusion support in massive bleeding does not increase patient risk of alloimmunization.
