Topical tranexamic acid inhibits fibrinolysis more effectively when formulated with self‐propelling particles
| Autor: | Matthew L. Statz, Eric Simonson, Richard Liggins, Jeff S. J. Yoon, Vionarica Gusti, Nathan J. White, Christian J. Kastrup, Amir Kazerooni, Michael M. Lee, James R. Baylis, Massimo Cau, Xu Wang, Alexander E. St. John |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Time Factors
Antifibrinolytic medicine.drug_class Administration Topical Drug Compounding medicine.medical_treatment Sus scrofa Hemorrhage Arteriotomy 030204 cardiovascular system & hematology Calcium Carbonate 03 medical and health sciences 0302 clinical medicine Antifibrinolytic agent Fibrinolysis medicine Coagulopathy Animals Humans Adverse effect Drug Carriers business.industry Hematology Carbon Dioxide medicine.disease Hyperfibrinolysis Antifibrinolytic Agents Mice Inbred C57BL Disease Models Animal Tranexamic Acid Anesthesia Female business Tranexamic acid medicine.drug |
| Zdroj: | Journal of Thrombosis and Haemostasis. 17:1645-1654 |
| ISSN: | 1538-7836 |
| Popis: | Background Endogenous fibrinolytic activation contributes to coagulopathy and mortality after trauma. Administering tranexamic acid (TXA), an antifibrinolytic agent, is one strategy to reduce bleeding; however, it must be given soon after injury to be effective and minimize adverse effects. Administering TXA topically to a wound site would decrease the time to treatment and could enable both local and systemic delivery if a suitable formulation existed to deliver the drug deep into wounds adequately. Objectives To determine whether self-propelling particles could increase the efficacy of TXA. Methods Using previously developed self-propelling particles, which consist of calcium carbonate and generate CO2 gas, TXA was formulated to disperse in blood and wounds. The antifibrinolytic properties were assessed in vitro and in a murine tail bleeding assay. Self-propelled TXA was also tested in a swine model of junctional hemorrhage consisting of femoral arteriotomy without compression. Results Self-propelled TXA was more effective than non-propelled formulations in stabilizing clots from lysis in vitro and reducing blood loss in mice. It was well tolerated when administered subcutaneously in mice up to 300 to 1000 mg/kg. When it was incorporated in gauze, four of six pigs treated after a femoral arteriotomy and without compression survived, and systemic concentrations of TXA reached approximately 6 mg/L within the first hour. Conclusions A formulation of TXA that disperses the drug in blood and wounds was effective in several models. It may have several advantages, including supporting local clot stabilization, reducing blood loss from wounds, and providing systemic delivery of TXA. This approach could both improve and simplify prehospital trauma care for penetrating injury. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text