Therapeutic Plasma Concentration of Epsilon Aminocaproic Acid in the Northern Elephant Seal (Mirounga angustirostris)
Drugs that inhibit fibrinolysis, such as epsilon aminocaproic acid (EACA), are a potential novel therapy for hemostatic disorders of zoological species. Although, to our knowledge, anti-fibrinolytic drugs are not commonly applied in zoo medicine, 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 usefully and safely applied to a novel species.2,7 Citrated plasma from 25 healthy NES pups was collected and pooled for use in this study. An in vitro model of hyperfibrinolysis using thromboelastography (TEG) was adapted for NES plasma from previously published protocols.2,7 Increasing doses of tissue plasminogen activator were added to pooled NES plasma to achieve complete, rapid fibrinolysis as documented by TEG. Fibrinolysis was then inhibited by adding increasing doses of EACA. We used the TEG parameter of estimated percent lysis (EPL) to indicate degree of fibrinolysis and performed regression analysis of the arcsin square transform of EPL against EACA concentration, to estimate the minimum concentration of EACA required to completely inhibit fibrinolysis for 30 minutes after maximum clot strength was reached (EPL=0%). This analysis yielded an estimated therapeutic EACA plasma concentration of 85 μg/ml (95% confidence interval = 73.8–96.8 μg/ml).
1. CRASH-2 Trial Collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomized, placebo-controlled trial. Lancet. 2010;376(9734):23–32.
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, Lowenstine LJ, Trupkiewitz J, Smith D, Royal B, Strubel I. Baseline 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, Lowenstine L, Werner L, Spraker T, et al. Nematode (Otostrongylus circumlitus) infestation of northern elephant seals (Mirounga angustirostris) stranded along the central California coast. Marine Mammal Science. 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. http://researchonline.lshtm.ac.uk/1301/. Accessed October 1, 2013. (VIN editor: link was not accessible as of 12/7/2020.)
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(1):35–39.