Randomized double‐blinded clinical trial on acute transfusion reactions in dogs receiving leukoreduced versus nonleukoreduced packed red blood cells

Abstract

Background: Leukoreduction of blood products is commonly performed in human medicine, but its effect on outcome or incidence of transfusion reactions (TRs) in dogs is unknown.Objectives: To prospectively evaluate the incidence of acute TRs in, and the outcome of, dogs receiving either leukoreduced (LR) or nonleukoreduced (N-LR) packed red blood cells (PRBC).Animals: Dogs (n = 194) administered PRBC between August 2017 and June 2020.Methods: Prospective randomized double-blinded clinical trial. Dogs were randomized to receive either LR or N-LR PRBC and clinicians, nurses and investigators were blinded to the group allocations. The incidence of TRs, change in PCV, hospitalization duration, and survival to discharge were recorded.Results: Out of the 194 dogs, 96 received LR and 98 received N-LR PRBCs. The mean 12-hour change in PCV value was +9.22% (SD 5.27%) for dogs that received N-LR and +10.69% (SD 6.44%) for dogs that received LR PRBC (effect size 0.26, 95% confidence interval [CI] À0.02 to 0.55), which was not significantly different (P = .08). TRs were documented in 16/194 (8.24%) dogs, with 1/194 (0.51%) being a mild allergic reaction, while 15/194 (7.73%) had suspected febrile nonhemolytic TRs (FNHTRs). FNHTR incidence was not significantly different between the LR (6/96, 6.25%, 95% CI 2.8-13.56) and N-LR (9/98, 9.18%, 95% CI 4.92-17.11) groups

Effect of leukoreduction on inflammation in critically ill dogs receiving red blood cell transfusions: A randomized blinded controlled clinical trial

“…However, we believe our trial best reflects clinical practice where variably aged blood will be available for any given transfusion and therefore would provide the most relevant data regarding the effect of LR on post-transfusion inflammation. The median age of transfused RBC bags in our study was not different between groups, at 21 (14-31) days for LR and 25 (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34) days for NLR. From previous in vitro analyses, we expected accumulation of IL-8 in NLR but not in LR RBC bags over time, with the highest concentration in older NLR bags.…”

“…Finally, our study was likely underpowered to detect a between-group difference in development of FNHTR, given its low reported incidence. 6,22 Although many large retrospective studies in people have identified a significant reduction in FNHTR incidence after implementation of leukoreduction, the effect size was small. 34,35 Future studies investigating the incidence of FNHTR with…”

“…This randomization and blinding protocol prevented the main enrollment problems seen in similar clinical trials, including missed enrollment because of lack of LR blood present in the blood bank, 21 and excluded dogs because of requirement for multiple transfusions. 21 , 22 Although our protocol led to all RBC‐transfused dogs at the study sites receiving blood that had been prepared for the study, regardless of their enrollment in the study, the clinical balance between LR and NLR RBC precluded this feature from being of ethical concern. In consideration of planning a larger multicenter clinical trial focused on clinical outcomes, our protocol would be easy to implement at any veterinary institution with its own blood bank and dedicated blood bank technician.…”

“…Finally, our study was likely underpowered to detect a between‐group difference in development of FNHTR, given its low reported incidence. 6 , 22 Although many large retrospective studies in people have identified a significant reduction in FNHTR incidence after implementation of leukoreduction, the effect size was small. 34 , 35 Future studies investigating the incidence of FNHTR with administration of LR compared with NLR RBC in dogs should plan to enroll a larger number of dogs and use the definition for FNHTR recently published in the Association of Veterinary Hematology and Transfusion Medicine Transfusion Reaction Small Animal Consensus Statement: a body temperature >39°C coupled with an increase of at least 1°C from pre‐transfusion body temperature during or within 4 hours of the completion of a blood transfusion, provided external warming, infection, and other types of transfusion reactions have been ruled out.…”

“… 5 This effect has not yet been demonstrated in more heterogenous populations of critically ill dogs. Two recently published blinded randomized clinical trials compared biomarkers of inflammation 21 or incidence of acute transfusion reactions 22 between critically ill dogs administered either LR or NLR RBC, and both trials found no difference between groups for either outcome. Both trials included relatively large proportions (57% 21 and 47% 22 ) of dogs with immune‐mediated diseases for which immunosuppressive medications were administered.…”