Tranexamic Acid Reduces Large Traumatic Bleeding and Mortality in Murine Iron Deficiency Anemia By Mechanisms Beyond Control of Fibrinolysis

Introduction Iron deficiency anemia (IDA) is common. Some clinical evidence suggests that IDA may aggravate traumatic hemorrhage and compromise outcomes. To study if IDA influences traumatic hemorrhage, coagulopathy, and mortality we developed a model of traumatic liver injury with and without tranexamic acid (TXA) in mice with dietary IDA and compared the results to control mice and mice after parenteral iron rescue. Materials and Methods Severe IDA was generated in C57BL/6J mice by starting an iron-deficient diet in 3-week-old mice for 8 weeks (+/- 1 mg intraperitoneal iron dextran 2 weeks before trauma). Control mice were fed a normal laboratory diet. IDA was confirmed by complete blood count, red cell indices, and liver iron. Mice (≈20 per group) were pre-treated with saline or TXA (10mg/kg) and subjected to liver laceration. Blood loss (weighing blood-soaked sponges from the abdomen), coagulopathy [APTT, Factor (F)II, FV, FVIII, FX, and fibrinogen), thrombin-antithrombin (TAT) and plasmin-antiplasmin (PAP) complexes] were analyzed at 60 minutes after trauma Cytokine levels (IL-1α, IL-1β, IL-2, IL-6, IL-10, MCP-1, RANTES, and TNFα) were measured at baseline, 60 minutes and 6 hours post-trauma. Data were expressed as median and compared by Mann-Whitney test. Seven-day survival was analyzed using Kaplan-Meier curves. Results IDA manifested as hypochromic/microcytic anemia with significantly lower hematocrits compared to normal controls (32% vs 48%, p=