Computational model of tranexamic acid on urokinase mediated fibrinolysis.
Antifibrinolytic Agents
/ therapeutic use
Blood Coagulation
/ genetics
Blood Coagulation Disorders
/ blood
Computer Simulation
Fibrin
/ genetics
Fibrin Clot Lysis Time
Fibrinolysin
/ genetics
Fibrinolysis
/ drug effects
Hemorrhage
/ blood
Humans
Membrane Proteins
/ genetics
Mortality
Pregnancy-Associated alpha 2-Macroglobulins
/ genetics
Thrombin
/ genetics
Tranexamic Acid
/ therapeutic use
Urokinase-Type Plasminogen Activator
/ genetics
Wounds and Injuries
/ blood
alpha 1-Antitrypsin
/ genetics
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
06
02
2020
accepted:
09
05
2020
entrez:
27
5
2020
pubmed:
27
5
2020
medline:
15
8
2020
Statut:
epublish
Résumé
Understanding the coagulation process is critical to developing treatments for trauma and coagulopathies. Clinical studies on tranexamic acid (TXA) have resulted in mixed reports on its efficacy in improving outcomes in trauma patients. The largest study, CRASH-2, reported that TXA improved outcomes in patients who received treatment prior to 3 hours after the injury, but worsened outcomes in patients who received treatment after 3 hours. No consensus has been reached about the mechanism behind the duality of these results. In this paper we use a computational model for coagulation and fibrinolysis to propose that deficiencies or depletions of key anti-fibrinolytic proteins, specifically antiplasmin, a1-antitrypsin and a2-macroglobulin, can lead to worsened outcomes through urokinase-mediated hyperfibrinolysis.
Identifiants
pubmed: 32453766
doi: 10.1371/journal.pone.0233640
pii: PONE-D-20-03512
pmc: PMC7250412
doi:
Substances chimiques
Antifibrinolytic Agents
0
Membrane Proteins
0
PLAU protein, human
0
Pregnancy-Associated alpha 2-Macroglobulins
0
alpha 1-Antitrypsin
0
Tranexamic Acid
6T84R30KC1
Fibrin
9001-31-4
Thrombin
EC 3.4.21.5
Fibrinolysin
EC 3.4.21.7
Urokinase-Type Plasminogen Activator
EC 3.4.21.73
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0233640Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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