Efficacy and safety of CounterFlow in animal models of hemorrhage

Introduction: Hemorrhage is a major cause of battlefield mortality, contributing to 91% of potentially survivable combat-related deaths. Death from hemorrhage often occurs in pre-hospital settings, and more efficacious hemorrhage control interventions are needed to extend survival and enable casualties to reach definitive surgery. CounterFlow is a novel topical hemostatic agent that uses self-propelling particles to deliver thrombin and tranexamic acid against active bleeding. It achieves and maintains hemostasis at the site of injury through a combination of mechanical, biological, and chemical effects. Methods: All literature in which CounterFlow was tested in animal models of hemorrhage was reviewed to compile its preclinical safety and efficacy as a hemostatic agent. Results: CounterFlow extended survival and halted hemorrhage in multiple animal models that mimicked common and deadly injuries encountered in military and civilian settings, including junctional wounds, surgical bleeding, non-compressible intra-abdominal hemorrhage, and upper gastrointestinal bleeding. Thromboembolism, tissue damage, and toxicity were not observed. Discussion: This narrative review discusses the animal models that have been used to investigate CounterFlow as a hemostatic agent for pre-hospital hemorrhage control. Future directions and potential expansion for civilian use are also considered. LAY SUMMARY The efficacy of current hemostatic technologies is limited by several factors. Outward blood flow washes hemostatic drugs away from the wound, and hemostatic drugs often require focus, training, and time to use correctly, are highly specific to one type of injury, or pose severe safety risks. CounterFlow is a novel product that could potentially save military and civilian lives by stopping heavy bleeding from a variety of organs and other bodily locations that current technology cannot easily treat. Upon contact with blood, CounterFlow releases bursts of gas to safely self-propel bio-degradable clot-forming and clot-stabilizing drugs against blood flow, delivering them to the source of bleeding. This unique mechanism allows CounterFlow to be applied quickly to a wide assortment of wounds and to act effectively with little management after application. CounterFlow was tested in multiple animal models representing common and deadly bleeding scenarios, including internal bleeding, care under fire without compression, and surgical bleeding, and it was found to outperform current care options by stopping bleeds faster and increasing survival times. CounterFlow is also safe to use and biocompatible. This narrative review summarizes studies testing the effectiveness and safety of CounterFlow, discusses useful applications, and describes future plans for the product.