Epsilon Aminocaproic Acid in the Northern Elephant Seal (Mirounga angustirostris): A Novel Anti-Fibrinolytic Therapy for Hemostatic Disorders
IAAAM 2015
Shawn P. Johnson1*; Daniel J. Fletcher2; Sarrah W. Kaye2
1The Marine Mammal Center, Sausalito, CA, USA; 2Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA

Abstract

Drugs that inhibit fibrinolysis, such as epsilon aminocaproic acid (EACA), are a potential novel therapy for hemostatic disorders of zoological species. Currently anti-fibrinolytic drugs are not commonly applied in zoo and wildlife medicine, but they are of increasing interest in human and companion animal medicine to prevent bleeding due to surgery, trauma, and other causes.1,5,6 One potential application of EACA is treatment of Northern elephant seals (NES) with Otostrongylus arteritis, a hemorrhagic diathesis associated with aberrant larval migration of Otostrongylus circumlitus.3,4 Therapeutic plasma concentration of EACA varies across species, from 5.82 µg/ml in horses up to 130 µg/ml in humans, necessitating investigation before the drug can be safely and effectively applied to a novel species.2,7 In order to determine the therapeutic plasma concentration of EACA for NES, an in vitro model of hyperfibrinolysis using thromboelastography (TEG) was adapted for NES plasma from previously published protocols.2,7 The minimum therapeutic plasma concentration of EACA required to completely inhibit fibrinolysis for 30 minutes after maximum clot strength was achieved was estimated at 85 µg/ml (95% confidence interval = 73.8–96.8 µg/ml). A pharmacokinetic study was performed using single oral doses of EACA at 50, 75, and 100 mg/kg to determine the oral dose and frequency required to achieve therapeutic plasma concentrations of EACA in NES. Due to the limited treatment options available for NES with severe bleeding, this drug could represent a cost-effective, efficacious alternative therapy for animals that might otherwise experience lethal hemorrhage.

Acknowledgements

This project was generously supported by the AAZV Wild Animal Health Fund. We thank Carlos Rios for his laboratory support and the volunteers of The Marine Mammal Center for their hard work in caring for the seals.

* Presenting author

Literature Cited

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2.  Fletcher DJ, Brainard BM, Epstein K, Radcliffe R, Divers T. Therapeutic plasma concentrations of epsilon aminocaproic acid and tranexamic acid in horses. J Vet Intern Med. 2013;27(6):1589–1595.

3.  Gulland FMD, Werner L, O'Neill SO, et al. Base line coagulation assay values for Northern elephant seals (Mirounga angustirostris) and disseminated intravascular coagulation in this species. J Wildl Dis. 1996;32(3):536–540.

4.  Gulland FMD, Beckmen K, Burek K, et al. Nematode (Otostrongylus circumlitis) infestation of Northern elephant seals (Mirounga angustirostris) stranded along the central California coast. Mar Mamm Sci. 1997;13(3):446–459.

5.  Henry DA, Carless PA, Moxey AJ, O'Connell D, Stokes BJ, Fergusson DA, Ker K. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane database of systematic reviews (online). 2011. Available from: researchonline.lshtm.ac.uk/1301.

6.  Kol A, Borjesson DL. Application of thromboelastography/thromboelastometry to veterinary medicine. Vet Clin Pathol. 2010;39(4):405–416.

7.  Nielsen VG, Cankovic L, Steenwyk BL. Epsilon-aminocaproic acid inhibition of fibrinolysis in vitro: should the 'therapeutic' concentration be reconsidered? Blood Coagul Fibrinolysis. 2007;18:35–39.

  

Speaker Information
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Shawn P. Johnson
The Marine Mammal Center
Sausalito, CA, USA


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