Gauze with self-propelling microparticles containing thrombin and tranexamic acid drastically improved survival in a swine model of lethal hemorrhage

摘要

Introduction: Severe bleeding from large arterial wounds is a leading cause of death after trauma. Hemostatic gauzes containing coagulation activators are currently used to pack and compress wounds but are less effective in anatomical locations where compression cannot be performed, likely because their activators are pushed away from the site of vessel injury by the hemorrhaging blood. Gauze impregnated with self-propelling microparticles that disperse hemostatic activators throughout the wound, including upstream against hemorrhage flow, may be useful in these situations. Methods: A self-propelling hemostatic bandage was created by binding thrombin to calcium carbonate microparticles and coating these particles on cotton bandage in the presence of solid protonated tranexamic acid (TXA). Contact with blood causes brisk release of CO2 and propulsion of microparticles against flowing blood to deliver the thrombin and induce hemostasis. Non-protonated TXA was substituted to form a non-propelling control. Bleeding was induced in 29 immature female swine using a 5 mm femoral arteriotomy. Pigs were randomized into 1 of 4 packing interventions without wound compression: negative control, kaolin hemostatic gauze control (Combat Gauze™) (KG), propelled thrombin gauze (PTG), or non-propelled thrombin gauze control (NPTG). All animals then received intravenous fluids to restore blood pressure for up to 3 hours. Survival was compared using Kaplan-Meier log rank, and continuous variables (i.e., blood loss and Laboratory values) were compared using repeated measures ANOVA. Results: Survival was improved with PTG (3-hr survival: 8/8,100%) compared to KG (3/8,37.5%, p=0.01) and compared to NPTG (2/8,25.0%, p=0.01). Total and post-intervention external blood loss were similar in all gauze groups (p＞0.05). Thromboelastogram maximum amplitude was higher with PTG compared to NPTG at 150 minutes but was otherwise not significantly different. Fibrinogen concentration did not differ across groups. Discussion: Propelled thrombin gauze improved survival in this lethal bleeding model. Self-propelling particles could be used to deliver a number of pro-thrombotic or wound-healing agents throughout an actively hemorrhaging wound to promote hemostasis and recovery.