1. Bills TK, Smith JB, Silver MJ. Selective release of archidonic acid from the phospholipids of human platelets in response to thrombin. J Clin Invest 1977; 60: 1–6.
2. Marcinkiewicz E, Grodzinska L, Gryglewski RJ. Platelet aggregation and thromboxane A2 formation in cat platelet rich plasma. Pharmacol Res Commun 1978; 10: 1–12.
3. Ting HJ, Murad JP, Espinosa EV, et al. Thromboxane A2 receptor: biology and function of a peculiar receptor that remains resistant for therapeutic targeting. J Cardiovasc Pharmacol Ther 2012; 17: 248–259.
4. FitzGerald GA, Pedersen AK, Patrono C. Analysis of prostacyclin and thromboxane biosynthesis in cardiovascular disease. Circulation 1983; 67: 1174–1177.
5. Hoh CM, Smith SA, McMichael MA, et al. Evaluation of effects of low-dose aspirin administration on urinary thromboxane metabolites in healthy dogs. Am J Vet Res 2011; 72: 1038–1045.
6. Roberts LJ II, Sweetman BJ, Oates JA. Metabolism of thromboxane B2 in man. Identification of twenty urinary metabolites. J Biol Chem 1981; 256: 8384–8393.
7. Catella F, Nowak J, Fitzgerald GA. Measurement of renal and non-renal eicosanoid synthesis. Am J Med 1986; 81: 23–29.
8. Westlund P, Kumlin M, Nordenstrom A, et al. Circulating and urinary thromboxane B2 metabolites in the rabbit: 11-dehydro-thromboxane B2 as parameter of thromboxane production. Prostaglandins 1986; 31: 413–443.
9. Catella F, Healy D, Lawson JA, et al. 11-Dehydrothromboxane B2: a quantitative index of thromboxane A2 formation in the human circulation. Proc Natl Acad Sci U S A 1986; 83: 5861–5865.
10. Kawamura M, Harada Y, Katori M. Evaluation of plasma 11-dehydro-thromboxane B2 as an indicator for thromboxane A2 synthesis in vivo in laboratory animals. Thromb Res 1995; 77: 465–474.
11. Borgeat K, Wright J, Garrod O, et al. Arterial thromboembolism in 250 cats in general practice: 2004–2012. J Vet Intern Med 2014; 28: 102–108.
12. Smith SA, Tobias AH, Jacob KA, et al. Arterial thromboembolism in cats: acute crisis in 127 cases (1992–2001) and long-term management with low-dose aspirin in 24 cases. J Vet Intern Med 2003; 17: 73–83.
13. Butler HC. An investigation into the relationship of an aortic embolus to posterior paralysis in the cat. J Small Anim Pract 1971; 12: 141–158.
14. Helenski CA, Ross JN Jr. Platelet aggregation in feline cardiomyopathy. J Vet Intern Med 1987; 1: 24–28.
15. Tablin F, Schumacher T, Pombo M, et al. Platelet activation in cats with hypertrophic cardiomyopathy. J Vet Intern Med 2014; 28: 411–418.
16. National Institutes of Health. Guide for the care and use of laboratory animals. 8th ed. Washington, DC: National Academies Press, 2011. Available at: grants.nih.gov/grants/olaw/Guide-for-the-Care-and-Use-of-Laboratory-Animals.pdf. Accessed January 15, 2014.
17. Dudley A, Thomason J, Fritz S, et al. Cyclooxygenase expression and platelet function in healthy dogs receiving low-dose aspirin. J Vet Intern Med 2013; 27: 141–149.
18. Thomason J, Lunsford K, Stokes J, et al. The effects of cyclosporine on platelet function and cyclooxygenase expression in normal dogs. J Vet Intern Med 2012; 26: 1389–1401.
19. Hall JA, Brockman JA, Jewell DE. Dietary fish oil alters the lysophospholipid metabolomic profile and decreases urinary 11-dehydro thromboxane B(2) concentration in healthy Beagles. Vet Immunol Immunopathol 2011; 144: 355–365.
20. Maddens BE, Daminet S, Demeyere K, et al. Validation of immunoassays for the candidate renal markers C-reactive protein, immunoglobulin G, thromboxane B2 and retinol binding protein in canine urine. Vet Immunol Immunopathol 2010; 134: 259–264.
21. Shen L, Matsunami Y, Quan N, et al. In vivo oxidation, platelet activation and simultaneous occurrence of natural immunity in atherosclerosis-prone mice. Isr Med Assoc J 2011; 13: 278–283.
22. Nakamura A, Nagaya N, Obata H, et al. Oral administration of a novel long-acting prostacyclin agonist with thromboxane synthase inhibitory activity for pulmonary arterial hypertension. Circ J 2013; 77: 2127–2133.
23. Dharmasaroja PA, Sae-Lim S. Comparison of aspirin response measured by urinary 11-dehydrothromboxane B2 and VerifyNow aspirin assay in patients with ischemic stroke. J Stroke Cerebrovasc Dis 2014; 23: 953–957.
24. Karon BS, Wockenfus A, Scott R, et al. Aspirin responsiveness in healthy volunteers measured with multiple assay platforms. Clin Chem 2008; 54: 1060–1065.
25. Baltzer WI, McMichael MA, Ruaux CG, et al. Measurement of urinary 11-dehydro-thromboxane B2 excretion in dogs with gastric dilatation-volvulus. Am J Vet Res 2006; 67: 78–83.
26. McConnell JP, Cheryk LA, Durocher A, et al. Urinary 11-dehydro-thromboxane B(2) and coagulation activation markers measured within 24 h of human acute ischemic stroke. Neurosci Lett 2001; 313: 88–92.
27. Norman EJ, Barron RC, Nash AS, et al. Prevalence of low automated platelet counts in cats: comparison with prevalence of thrombocytopenia based on blood smear estimation. Vet Clin Pathol 2001; 30: 137–140.
28. Davi G, Di Minno G, Coppola A, et al. Oxidative stress and platelet activation in homozygous homocystinuria. Circulation 2001; 104: 1124–1128.
29. Freese R, Vaarala O, Turpeinen AM, et al. No difference in platelet activation or inflammation markers after diets rich or poor in vegetables, berries and apple in healthy subjects. Eur J Nutr 2004; 43: 175–182.
30. Cavalca V, Minardi F, Scurati S, et al. Simultaneous quantification of 8-iso-prostaglandin-F(2alpha) and 11-dehydro thromboxane B(2) in human urine by liquid chromatography-tandem mass spectrometry. Anal Biochem 2010; 397: 168–174.
31. Hishinuma T, Yu GS, Takabatake M, et al. Analysis of the thromboxane/prostacyclin balance in human urine by gas chromatography/selected ion monitoring: abnormalities in diabetics. Prostaglandins Leukot Essent Fatty Acids 1996; 54: 445–449.
32. Catella F, FitzGerald GA. Paired analysis of urinary thromboxane B2 metabolites in humans. Thromb Res 1987; 47: 647–656.
33. Fitzgerald DJ, Roy L, Catella F, et al. Platelet activation in unstable coronary disease. N Engl J Med 1986; 315: 983–989.
34. Yamanobe S, Nakagawa Y, Hishinuma T, et al. Analysis of urinary 11-dehydrothromboxane B2 in patients with occluded retinal vein using GC/SIM. Prostaglandins Leukot Essent Fatty Acids 1998; 58: 65–68.
35. Koudstaal PJ, Ciabattoni G, van Gijn J, et al. Increased thromboxane biosynthesis in patients with acute cerebral ischemia. Stroke 1993; 24: 219–223.
36. Vesterqvist O, Edhag O, Green K, et al. In vivo production of thromboxane in acute human myocardial infarction: a preliminary study. Thromb Res 1985; 37: 459–464.
37. Brainard BM, Meredith CP, Callan MB, et al. Changes in platelet function, hemostasis, and prostaglandin expression after treatment with nonsteroidal anti-inflammatory drugs with various cyclooxygenase selectivities in dogs. Am J Vet Res 2007; 68: 251–257.
38. Cathcart CJ, Brainard BM, Reynolds LR, et al. Lack of inhibitory effect of acetylsalicylic acid and meloxicam on whole blood platelet aggregation in cats. J Vet Emerg Crit Care (San Antonio) 2012; 22: 99–106.
39. Catella F, Lawson JA, Fitzgerald DJ, et al. Analysis of multiple thromboxane metabolites in plasma and urine. Adv Prostaglandin Thromboxane Leukot Res 1987; 17B:611–614.
40. Westlund P, Granstrom E, Kumlin M, et al. Identification of 11-dehydro-TXB2 as a suitable parameter for monitoring thromboxane production in the human. Prostaglandins 1986; 31: 929–960.
41. Patrono C, Ciabattoni G, Patrignani P, et al. Evidence for a renal origin of urinary thromboxane B2 in health and disease. Adv Prostaglandin Thromboxane Leukot Res 1983; 11: 493–498.
42. Welles EG, Boudreaux MK, Crager CS, et al. Platelet function and antithrombin, plasminogen, and fibrinolytic activities in cats with heart disease. Am J Vet Res 1994; 55: 619–627.
43. Jandrey KE, Norris JW, MacDonald KA, et al. Platelet function in clinically healthy cats and cats with hypertrophic cardiomyopathy: analysis using the Platelet Function Analyzer-100. Vet Clin Pathol 2008; 37: 385–388.
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OBJECTIVE To determine the predominant thromboxane (TX) metabolite in urine of healthy cats, evaluate whether the method of sample collection would impact concentration of that metabolite, and propose a reference interval for that metabolite in urine of healthy cats.
ANIMALS 17 cats (11 purpose-bred domestic shorthair cats, 5 client-owned domestic shorthair cats, and 1 client-owned Persian cat).
PROCEDURES All cats were deemed healthy on the basis of results for physical examination, a CBC, serum biochemical analysis, urinalysis, and measurement of prothrombin time and activated partial thromboplastin time. Voided and cystocentesis urine samples (or both) were collected. Aliquots of urine were stored at −80°C until analysis. Concentrations of TXB2, 11-dehydroTXB2, and 2,3 dinorTXB2 were measured with commercially available ELISA kits. Urinary creatinine concentration was also measured.
RESULTS 11-dehydroTXB2 was the most abundant compound, representing (mean ± SD) 59 ± 18% of the total amount of TX detected. In all samples, the concentration of 11-dehydroTXB2 was greater than that of 2,3 dinorTXB2 (mean, 4.2 ± 2.7-fold as high). Mean concentration of 11-dehydroTXB2 for the 17 cats was 0.57 ± 0.47 ng/mg of creatinine. A reference interval (based on the 5% to 95% confidence interval) of 0.10 to 2.1 ng of 11-dehydroTXB2/mg of creatinine was proposed for healthy cats.
CONCLUSIONS AND CLINICAL RELEVANCE In this study, 11-dehydroTXB2 was the major TX metabolite in feline urine. Measurement of this metabolite may represent a noninvasive, convenient method for monitoring in vivo platelet activation in cats at risk for thromboembolism.