BACKGROUND AND OBJECTIVES Studies in mice suggest that rapid transfusions of red blood cells (RBCs), refrigerator stored for longer durations, induce a pro-inflammatory cytokine response. Studies in human neonates confirm these findings; however, to date, adult human studies have failed to replicate these findings. We used healthy research dogs to begin to examine the factors affecting the cytokine response to transfusion. MATERIALS AND METHODS In a prospective study, healthy dogs were randomized for two autologous packed RBC transfusions after 7 (i.e. “fresh”) and 28 (“old”) days of storage, or after 28 and 7 days of storage, with or without pre-storage leukoreduction (LR). RESULTS No significant differences were observed between LR and non-LR transfusions for all circulating analytes measured following transfusion. A pro-inflammatory cytokine response, exemplified by monocyte chemoattractant protein-1, was observed 6 hours after only old RBC transfusions, irrespective of infusion rate (P<0.001). This response was accompanied by increased neutrophil counts (P<0.001) and decreased platelet counts (P<0.001). CONCLUSION In healthy dogs, old RBC transfusions induce inflammation, which is unaffected by infusion rate.

BackgroundRecognition of the feline red blood cell (RBC) antigen Mik and the presence of naturally occurring anti‐Mik antibodies resulting in acute hemolytic transfusion reactions prompted the recommendation to perform a crossmatch before a cat's first RBC transfusion, but this guideline has not yet become a standard practice.ObjectiveTo determine the prevalence of naturally occurring non‐AB alloantibodies detectable by tube crossmatch, and to compare transfusion outcomes in cats with and without a crossmatch performed.AnimalsThree hundred cats that received an RBC transfusion, with or without a major crossmatch performed.MethodsRetrospective study.ResultsMajor crossmatch incompatibilities were documented in 23 of 154 transfusion‐naive cats (14.9%) and in 15 of 55 previously transfused cats (27%; P = 0.042). Type‐specific packed RBCs (pRBCs) were administered to 167 and 82 cats with and without a crossmatch, respectively. Median volume of pRBCs administered during the first transfusion was 5.3 mL/kg (range, 2.4‐18 mL/kg). Median change in PCV scaled to dose of pRBCs was +0.8%/mL/kg; administration of crossmatch‐compatible pRBCs was not associated with a greater increase in PCV. Febrile transfusion reactions occurred more often in cats that received non‐crossmatched (10.1%) compared to crossmatched (2.5%) pRBCs (P = 0.022). Seventy‐six percent of cats that received pRBC transfusions survived to hospital discharge. A crossmatch was not associated with improved survival to discharge or at 30 or 60 days posttransfusion.Conclusions and Clinical ImportanceThe prevalence of naturally occurring non‐AB incompatibilities is sufficiently high to justify the recommendation to perform a crossmatch before all (including the first) RBC transfusions in cats.

Background: Transfusion of red blood cells (RBCs) stored for longer durations induces hemolysis and inflammatory cytokine production in murine and canine models. Despite immune system activation by stored RBCs, human randomized trials suggest that fresher RBC transfusions do not improve clinical outcomes. We hypothesized that underlying recipient hemolysis may affect cytokine responses to older RBC transfusions. Study design and methods: C57BL/6 mouse cohorts were infused with anti-TER119 antibody to induce hemolysis, rabbit anti-platelet antiserum to induce immune thrombocytopenia (ITP), or appropriate control antibodies. Two days later, mice were transfused with fresh or stored RBCs. Furthermore, in a prospective, randomized, blinded trial, 38 client-owned dogs with primary autoimmune hemolytic anemia (AIHA) and two dogs with ITP, requiring RBC transfusion, were enrolled and randomized to receive fresh (≤7 days) or old (≥21 days) stored RBC transfusions. Monocyte chemoattractant protein (MCP)-1 levels were assessed at defined times after transfusion. Results: Prior immune-mediated hemolysis blunted the MCP-1 response to stored RBC transfusion in mice (361 ± 111 pg/ml vs. 6836 ± 1528 pg/ml in mice with immune hemolysis vs. ITP, respectively; mean ± SD; p < .0001). Although hemolysis markers increased after transfusion of older RBCs, the cytokine response was also muted in dogs with AIHA. No differences in morbidity or mortality were evident comparing dogs randomized to fresh or old RBCs. Conclusion:These data suggest that underlying hemolysis blunts inflammatory responses to old RBC transfusions. The canine data support randomized trial results suggesting a lack of clinical benefit with fresh RBC transfusions in subjects with underlying, baseline hemolysis.

An SI > 1.0 is a sensitive and specific tool for detecting acute small volume blood loss in healthy dogs.

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