Effect of Deferoxamine on Post-Transfusion Iron, Inflammation, and In Vitro Microbial Growth in a Canine Hemorrhagic Shock Model: A Randomized Controlled Blinded Pilot Study

SIMPLE SUMMARY: Blood transfusions can be lifesaving but can also harm patients by causing inflammation and increasing the risk of infection. Harm may occur from increasing the amount of unbound iron in circulation. When it is not bound to special carriers, iron is toxic, causing inflammation and supporting bacterial growth. This study aimed to determine if giving deferoxamine, a drug designed to bind iron, just after a transfusion would prevent the increase in unbound iron and inflammation that occurs in dogs following blood transfusions. All dogs in the study had increased unbound iron levels and markers of inflammation after receiving a transfusion. However, when unbound iron levels and markers of inflammation were compared between dogs that received deferoxamine and dogs that received a placebo, there were no differences detected. Furthermore, deferoxamine did not slow the growth of bacteria within blood samples taken from dogs during the study compared to placebo. In conclusion, the dose of deferoxamine used in this study did not prevent inflammation in the transfused dogs nor did it inhibit bacterial growth in blood samples from these dogs. ABSTRACT: Red blood cell (RBC) transfusion is associated with recipient inflammation and infection, which may be triggered by excessive circulating iron. Iron chelation following transfusion may reduce these risks. The aim of this study was to evaluate the effect of deferoxamine on circulating iron and inflammation biomarkers over time and in vitro growth of Escherichia coli (E. coli) following RBC transfusion in dogs with atraumatic hemorrhage. Anesthetized dogs were subject to atraumatic hemorrhage and transfusion of RBCs, then randomized to receive either deferoxamine or saline placebo of equivalent volume (n = 10 per group) in a blinded fashion. Blood was sampled before hemorrhage and then 2, 4, and 6 h later. Following hemorrhage and RBC transfusion, free iron increased in all dogs over time (both p < 0.001). Inflammation biomarkers interleukin-6 (IL6), CXC motif chemokine-8 (CXCL8), interleukin-10 (IL10), and keratinocyte-derived chemokine (KC) increased in all dogs over time (all p < 0.001). Logarithmic growth of E. coli clones within blood collected 6 h post-transfusion was not different between groups. Only total iron-binding capacity was different between groups over time, being significantly increased in the deferoxamine group at 2 and 4 h post-transfusion (both p < 0.001). In summary, while free iron and inflammation biomarkers increased post-RBC transfusion, deferoxamine administration did not impact circulating free iron, inflammation biomarkers, or in vitro growth of E. coli when compared with placebo.