Topical tranexamic acid inhibits fibrinolysis more effectively when formulated with self-propelling particles.
Administration, Topical
Animals
Antifibrinolytic Agents
/ administration & dosage
Calcium Carbonate
/ chemistry
Carbon Dioxide
/ chemistry
Disease Models, Animal
Drug Carriers
Drug Compounding
Female
Fibrinolysis
/ drug effects
Hemorrhage
/ blood
Humans
Mice, Inbred C57BL
Sus scrofa
Time Factors
Tranexamic Acid
/ administration & dosage
acute traumatic coagulopathy
combat casualty care
hyperfibrinolysis
trauma-induced coagulopathy
Journal
Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
22
10
2018
accepted:
10
05
2019
pubmed:
31
5
2019
medline:
25
8
2020
entrez:
31
5
2019
Statut:
ppublish
Résumé
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. To determine whether self-propelling particles could increase the efficacy of TXA. Using previously developed self-propelling particles, which consist of calcium carbonate and generate CO 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. 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.
Sections du résumé
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 CO
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.
Identifiants
pubmed: 31145837
doi: 10.1111/jth.14526
pii: S1538-7836(22)03344-X
doi:
Substances chimiques
Antifibrinolytic Agents
0
Drug Carriers
0
Carbon Dioxide
142M471B3J
Tranexamic Acid
6T84R30KC1
Calcium Carbonate
H0G9379FGK
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1645-1654Subventions
Organisme : CIHR
ID : FDN‐148370
Pays : Canada
Organisme : CIHR
ID : MOP‐119426
Pays : Canada
Organisme : CIHR
ID : GSD‐146267
Pays : Canada
Organisme : CIHR
ID : MSH‐130166
Pays : Canada
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2019 International Society on Thrombosis and Haemostasis.
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