Comparative vertebrate fibrinolysis

Tentoni, Juan; Polini, Nélida Nora; Casanave, Emma Beatriz

doi:10.1007/s00580-010-0988-3

Cited by 10 publications

(8 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Compared to humans, horses have decreased plasminogen activity (66.5-98.1% versus 80-120%) and increased alpha-2 antiplasmin activity (154-240% versus 70-130%) and PAI-1 concentrations (28.2-33.6 U/mL versus <10 U/mL). [14][15][16] This combination of decreased profibrinolytic mediators and increased antifibrinolytic mediators could explain the decreased concentrations of EACA and TEA required to inhibit fibrinolysis in equine plasma in comparison to human plasma noted in this study.…”

Section: Discussionmentioning

confidence: 57%

“…Because such a high concentration of tPA was used in this model system, the differences in response to EACA and TEA between horses and humans in this study are unlikely the result of differences in endogenous tPA concentrations in the pooled plasma from the 2 species. Compared to humans, horses have decreased plasminogen activity (66.5–98.1% versus 80–120%) and increased alpha‐2 antiplasmin activity (154–240% versus 70–130%) and PAI‐1 concentrations (28.2–33.6 U/mL versus <10 U/mL) . This combination of decreased profibrinolytic mediators and increased antifibrinolytic mediators could explain the decreased concentrations of EACA and TEA required to inhibit fibrinolysis in equine plasma in comparison to human plasma noted in this study.…”

Section: Discussionmentioning

confidence: 58%

“…Therapeutic plasma concentrations of EACA and TEA have not been determined in horses, and current dosing recommendations for EACA (3.5 mg/kg/min for 15 minutes followed by 0.25 mg/kg/min for the treatment period) target therapeutic plasma concentrations established in humans . However, there is evidence that healthy horses may have decreased fibrinolytic activity compared to people, as indicated by lower basal plasminogen activity and increased α‐2 antiplasmin and plasminogen activator inhibitor‐1 (PAI‐1) activity in adult horses and foals . In addition, horses require 10‐fold higher concentrations of tissue plasminogen activator (tPA) to induce fibrinolysis in an in vitro assay compared to humans .…”

mentioning

confidence: 99%

“…11,13 However, there is evidence that healthy horses may have decreased fibrinolytic activity compared to people, as indicated by lower basal plasminogen activity and increased a-2 antiplasmin and plasminogen activator inhibitor-1 (PAI-1) activity in adult horses and foals. [14][15][16] In addition, horses require 10-fold higher concentrations of tissue plasminogen activator (tPA) to induce fibrinolysis in an in vitro assay compared to humans. 17 This suggests that EACA and TEA dosing targets based on human data may be excessive in horses.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Therapeutic Plasma Concentrations of Epsilon Aminocaproic Acid and Tranexamic Acid in Horses

Fletcher

Brainard

Epstein

et al. 2013

Veterinary Internal Medicne

View full text Add to dashboard Cite

Background: Antifibrinolytic drugs such as epsilon aminocaproic acid (EACA) and tranexamic acid (TEA) are used to treat various bleeding disorders in horses. Although horses are hypofibrinolytic compared to humans, dosing schemes have been derived from pharmacokinetic studies targeting plasma concentrations in humans.Hypothesis/Objectives: We hypothesized therapeutic plasma concentrations of antifibrinolytic drugs in horses would be significantly lower than in humans. Our objective was to use thromboleastography (TEG) and an in vitro model of hyperfibrinolysis to predict therapeutic concentrations of EACA and TEA in horses and humans.Animals: Citrated plasma collected from 24 random source clinically healthy research horses. Commercial pooled human citrated plasma with normal coagulation parameters was purchased.Methods: Minimum tissue plasminogen activator (tPA) concentration to induce complete fibrinolysis within 10 minutes was determined using serial dilutions of tPA in equine plasma. Results used to create an in vitro hyperfibrinolysis model with equine and human citrated plasma, and the minimum concentrations of EACA and TEA required to completely inhibit fibrinolysis for 30 minutes (estimated therapeutic concentrations) determined using serial dilutions of the drugs.Results: Estimated therapeutic concentrations of EACA and TEA were significantly lower in horses (5.82; 95% CI 3.77-7.86 lg/mL and 0.512; 95% CI 0.277-0.748 lg/mL) than in humans (113.2; 95% CI 95.8-130.6 lg/mL and 11.4; 95% CI 8.62-14.1 lg/mL).Conclusions and Clinical Importance: Current dosing schemes for EACA and TEA in horses may be as much as 209 higher than necessary, potentially increasing cost of treatment and risk of adverse effects.

show abstract

Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 58%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Therapeutic Plasma Concentrations of Epsilon Aminocaproic Acid and Tranexamic Acid in Horses

Fletcher

Brainard

Epstein

et al. 2013

Veterinary Internal Medicne

View full text Add to dashboard Cite

show abstract

“…6,7,28 Increased in vitro fibrinolytic activity in dogs, up to 6 times that of humans, has also been reported. 29,30 Multiple mechanisms for this hyperfibrinolysis have been suggested. Plasminogen activator activity in canine plasma is approximately 25% higher than in human plasma.…”

Section: Discussionmentioning

confidence: 99%