Decreased Circulating Red Cell Mass Induced by Intravenous Acepromazine Administration Alters Viscoelastic and Traditional Plasma Coagulation Testing Results in Healthy Horses
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Horses
2.2. In Vivo Acepromazine-Induced Anemia Model
2.3. Acepromazine Effect on Coagulation Ex Vivo
2.4. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Epstein, K.L. Coagulopathies in horses. Vet. Clin. N. Am. Equine Pract. 2014, 30, 437–452. [Google Scholar] [CrossRef] [PubMed]
- Byars, T.D.; Davis, D.; Divers, T.J. Coagulation in the equine intensive-care patient. Clin. Tech. Equine Pract. 2003, 2, 178–187. [Google Scholar] [CrossRef]
- Dolente, B.A.; Wilkins, P.A.; Boston, R.C. Clinicopathologic evidence of disseminated intravascular coagulation in horses with acute colitis. J. Am. Vet. Med. Assoc. 2002, 220, 1034–1038. [Google Scholar] [CrossRef] [PubMed]
- Welch, R.D.; Watkins, J.P.; Taylor, T.S.; Cohen, N.D.; Carter, G.K. Disseminated intravascular coagulation associated with colic in 23 horses (1984–1989). J. Vet. Intern. Med. 1992, 6, 29–35. [Google Scholar] [CrossRef] [PubMed]
- van Limburg Stirum, E.V.J.; Clark, N.V.; Lindsey, A.; Gu, X.; Thurkow, A.L.; Einarsson, J.I.; Cohen, S.L. Factors Associated with Negative Patient Experiences with Essure Sterilization. JSLS 2020, 24, e2019.00065. [Google Scholar] [CrossRef]
- Mendez-Angulo, J.L.; Mudge, M.C.; Couto, C.G. Thromboelastography in equine medicine: Technique and use in clinical research. Equine Vet. Educ. 2012, 24, 639–649. [Google Scholar] [CrossRef]
- Hartert, H. Blutgerinnungsstudien mit der Thrombelastographie, einem neuen Untersuchungsverfahren. Klin. Wochenschr. 1948, 26, 577–583. [Google Scholar] [CrossRef]
- Kang, Y.G.; Martin, D.J.; Marquez, J.; Lewis, J.H.; Bontempo, F.A.; Shaw, B.W.J.; Starzl, T.E.; Winter, P.M. Intraoperative Changes in Blood Coagulation and Thrombelastographic Monitoring in Liver Transplantation. Anesth. Analg. 1985, 64, 888–896. [Google Scholar] [CrossRef]
- Walsham, N.E.; Sherwood, R.A. Fecal calprotectin in inflammatory bowel disease. Clin. Exp. Gastroenterol. 2016, 9, 21–29. [Google Scholar] [CrossRef]
- Agarwal, S.; Abdelmotieleb, M. Viscoelastic testing in cardiac surgery. Transfusion 2020, 60, S52–S60. [Google Scholar] [CrossRef]
- Sinnott, V.B.; Otto, C.M. Use of thromboelastography in dogs with immune-mediated hemolytic anemia: 39 cases (2000–2008). J. Vet. Emerg. Crit. Care 2009, 19, 484–488. [Google Scholar] [CrossRef] [PubMed]
- Wagg, C.R.; Boysen, S.R.; Bédard, C. Thrombelastography in dogs admitted to an intensive care unit. Vet. Clin. Pathol. 2009, 38, 453–461. [Google Scholar] [CrossRef] [PubMed]
- Otto, C.M.; Rieser, T.M.; Brooks, M.B.; Russell, M.W. Evidence of hypercoagulability in dogs with parvoviral enteritis. J. Am. Vet. Med. Assoc. 2000, 217, 1500–1504. [Google Scholar] [CrossRef] [PubMed]
- Kristensen, A.T.; Wiinberg, B.; Jessen, L.R.; Andreasen, E.; Jensen, A.L. Evaluation of Human Recombinant Tissue Factor-Activated Thromboelastography in 49 Dogs with Neoplasia. J. Vet. Intern. Med. 2008, 22, 140–147. [Google Scholar] [CrossRef]
- Epstein, K.L.; Brainard, B.M.; Giguere, S.; Vrono, Z.; Moore, J.N. Serial viscoelastic and traditional coagulation testing in horses with gastrointestinal disease. J. Vet. Emerg. Crit. Care 2013, 23, 504–516. [Google Scholar] [CrossRef]
- Tennent-Brown, B.S.; Epstein, K.L.; Whelchel, D.D.; Giguère, S. Use of viscoelastic coagulation testing to monitor low molecular weight heparin administration to healthy horses. J. Vet. Emerg. Crit. Care 2013, 23, 291–299. [Google Scholar] [CrossRef]
- Mendez-Angulo, J.; Mudge, M.; Zaldivar-Lopez, S.; Vilar-Saavedra, P.; Couto, G. Thromboelastography in healthy, sick non-septic and septic neonatal foals. Aust. Vet. J. 2011, 89, 500–505. [Google Scholar] [CrossRef]
- McMichael, M.; Smith, S.A.; McConachie, E.L.; Lascola, K.; Wilkins, P.A. In-vitro hypocoagulability on whole blood thromboelastometry associated with in-vivo expansion of red cell mass in an equine model. Blood Coagul. Fibrinolysis 2011, 22, 424–430. [Google Scholar] [CrossRef]
- McMichael, M.A.; Smith, S.A.; Galligan, A.; Swanson, K.S. In vitro hypercoagulability on whole blood thromboelastometry associated with in vivo reduction of circulating red cell mass in dogs. Vet. Clin. Pathol. 2014, 43, 154–163. [Google Scholar] [CrossRef]
- Bishop, R.C.; Jonk, K.M.; Migliorisi, A.; Austin, S.M.; Mullins, E.C.; Wilkins, P.A. Increased packed cell volume alters point of care viscoelastic clotting parameters in horses. Equine Vet. J. 2024. Epub ahead of print. [Google Scholar] [CrossRef] [PubMed]
- Parry, B.W.; Anderson, G.A. Influence of acepromazine maleate on the equine haematocrit. J. Vet. Pharmacol. Ther. 1983, 6, 121–126. [Google Scholar] [CrossRef] [PubMed]
- Sutil, D.V.; Mattoso, C.R.S.; Volpato, J.; Weinert, N.C.; Costa, Á.; Antunes, R.R.; Muller, T.R.; Beier, S.L.; Tochetto, R.; Comassetto, F.; et al. Hematological and splenic Doppler ultrasonographic changes in dogs sedated with acepromazine or xylazine. Vet. Anaesth. Analg. 2017, 44, 746–754. [Google Scholar] [CrossRef] [PubMed]
- Fisher, D. Haematology and Biochemistry Effects of Acepromazine or Detomidine Sedation in Horses; University of Pretoria: Pretoria, South Africa, 2019. [Google Scholar]
- Kullmann, A.; Sanz, M.; Fosgate, G.T.; Saulez, M.N.; Page, P.C.; Rioja, E. Effects of xylazine, romifidine, or detomidine on hematology, biochemistry, and splenic thickness in healthy horses. Can. Vet. J. 2014, 55, 334–340. [Google Scholar]
- Persson, S.G.; Ekman, L.; Lydin, G.; Tufvesson, G. Circulatory effects of splenectomy in the horse. I. Effect on red-cell distribution and variability of haematocrit in the peripheral blood. Zentralbl. Vet. A 1973, 20, 441–455. [Google Scholar] [CrossRef]
- Ballard, S.; Shults, T.; Kownacki, A.A.; Blake, J.W.; Tobin, T. The pharmacokinetics, pharmacological responses and behavioral effects of acepromazine in the horse. J. Vet. Pharmacol. Ther. 1982, 5, 21–31. [Google Scholar] [CrossRef]
- Navas de Solis, C.; Foreman, J.H.; Byron, C.R.; Carpenter, R.E. Ultrasonographic measurement of spleen volume in horses. Comp. Exerc. Physiol. 2012, 8, 19–25. [Google Scholar] [CrossRef]
- Bishop, R.C.; Kemper, A.M.; Burges, J.W.; Jandrey, K.E.; Wilkins, P.A. Preliminary evaluation of reference intervals for a point-of-care viscoelastic coagulation monitor (VCM Vet) in healthy adult horses. J. Vet. Emerg. Crit. Care 2023, 33, 540–548. [Google Scholar] [CrossRef] [PubMed]
- Knych, H.K.; Seminoff, K.; McKemie, D.S.; Kass, P.H. Pharmacokinetics, pharmacodynamics, and metabolism of acepromazine following intravenous, oral, and sublingual administration to exercised Thoroughbred horses. J. Vet. Pharmacol. Ther. 2018, 41, 522–535. [Google Scholar] [CrossRef]
- R Core Team. R: A Language and Environment for Statistical Computing; R Foundation for Statistical Computing: Vienna, Austria, 2023. [Google Scholar]
- Kassambara, A. Ggpubr: ‘ggplot2’ Based Publication Ready Plots; R package Version 0.4.0. 2020. Available online: https://rpkgs.datanovia.com/ggpubr/ (accessed on 20 September 2024).
- Zhu, H. kableextra: Construct Complex Table with ‘kable’ and Pipe Syntax. 2023. Available online: https://cran.r-project.org/package=kableExtra (accessed on 20 September 2024).
- Makiyama, K. Magicfor: Magic Functions to Obtain Results from for Loops. 2016. Available online: https://github.com/hoxo-m/magicfor (accessed on 20 September 2024).
- Ataga, K.I.; Cappellini, M.D.; Rachmilewitz, E.A. β-Thalassaemia and sickle cell anaemia as paradigms of hypercoagulability. Br. J. Haematol. 2007, 139, 3–13. [Google Scholar] [CrossRef]
- Ng, K.F.J.; Lo, J.W.R. The Development of Hypercoagulability State, as Measured by Thrombelastography, Associated with Intraoperative Surgical Blood Loss. Anaesth. Intensive Care 1996, 24, 20–25. [Google Scholar] [CrossRef]
- Martinez, J.A.B.; Guerra, C.C.D.C.; Nery, L.E.; Jardim, J.R.D.B. Iron stores and coagulation parameters in patients with hypoxemic polycythemia secondary to chronic obstructive pulmonary disease: The effect of phlebotomies. Sao Paulo Med. J. 1997, 115, 1395–1402. [Google Scholar] [CrossRef] [PubMed]
- Shibata, J.; Hasegawa, J.; Siemens, H.J.; Wolber, E.; Dibbelt, L.; Li, D.; Katschinski, D.M.; Fandrey, J.; Jelkmann, W.; Gassmann, M.; et al. Hemostasis and coagulation at a hematocrit level of 0.85: Functional consequences of erythrocytosis. Blood 2003, 101, 4416–4422. [Google Scholar] [CrossRef] [PubMed]
- Olascoaga, A.; Vilar-Compte, D.; Poitevin-Chacon, A.; Contreras-Ruiz, J. Wound healing in radiated skin: Pathophysiology and treatment options. Int. Wound J. 2008, 5, 246–257. [Google Scholar] [CrossRef] [PubMed]
- Vicente-Ibarra, N.; Marín, F.; Pernías-Escrig, V.; Sandín-Rollán, M.; Núñez-Martínez, L.; Lozano, T.; Macías-Villaniego, M.J.; Carrillo-Alemán, L.; Candela-Sánchez, E.; Guzmán, E.; et al. Impact of anemia as risk factor for major bleeding and mortality in patients with acute coronary syndrome. Eur. J. Intern. Med. 2019, 61, 48–53. [Google Scholar] [CrossRef]
- Westenbrink, B.D.; Alings, M.; Granger, C.B.; Alexander, J.H.; Lopes, R.D.; Hylek, E.M.; Thomas, L.; Wojdyla, D.M.; Hanna, M.; Keltai, M.; et al. Anemia is associated with bleeding and mortality, but not stroke, in patients with atrial fibrillation: Insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. Am. Heart J. 2017, 185, 140–149. [Google Scholar] [CrossRef]
- Lippi, G.; Salvagno, G.L.; Ippolito, L.; Franchini, M.; Favaloro, E.J. Shortened activated partial thromboplastin time: Causes and management. Blood Coagul. Fibrinolysis 2010, 21, 459–463. [Google Scholar] [CrossRef]
- Tripodi, A.; Chantarangkul, V.; Martinelli, I.; Bucciarelli, P.; Mannucci, P.M. A shortened activated partial thromboplastin time is associated with the risk of venous thromboembolism. Blood 2004, 104, 3631–3634. [Google Scholar] [CrossRef]
- Lin, Q.; Li, T.; Ding, S.; Yu, Q.; Zhang, X. Anemia-Associated Platelets and Plasma Prothrombin Time Increase in Patients with Adenomyosis. J. Clin. Med. 2022, 11, 4382. [Google Scholar] [CrossRef]
- Segura, D.; Monreal, L. Poor reproducibility of template bleeding time in horses. J. Vet. Intern. Med. 2008, 22, 238–241. [Google Scholar] [CrossRef]
REF | T0 | T1 | T2 | p-Value | |
---|---|---|---|---|---|
PCV (%) | 32–42 | 39 (37.5, 40) A | 26 (25.5, 26.5) B | 34 (32, 34.5) C | <0.001 * |
TS (g/dL) | 5.5–7.3 | 7 (6.95, 7.95) | 6.9 (6.75, 7) | 7.2 (6.95, 7.2) | 0.15 |
RBC (×106 cells/μL) | 7.00–13.0 | 8.46 (8.19, 8.91) A | 5.48 (5.33, 6.02) B | 7.06 (6.61, 7.76) C | <0.001 * |
Hemoglobin (g/dL) | 11.0–19.0 | 13.85 (13.15, 14.43) A | 9.25 (8.98, 9.9) B | 11.8 (10.83, 12.43) C | <0.001 * |
Hematocrit (%) | 32.0–53.0 | 39.56 (38.4, 41.25) A | 27 (29.93, 28.43) B | 34.4 (31.98, 36.5) C | <0.001 * |
MCV (fL) | 32.0–53.0 | 47.55 (46.7, 48.43) | 48.2 (46.7, 49.08) | 48.35 (47.5, 49.33) | 0.79 |
MCH (pg) | 12.0–20.0 | 16.5 (15.58, 16.75) | 16.8 (16.38, 16.93) | 16.7 (16.25, 16.93) | 0.632 |
MCHC (g/dL) | 30.0–39.0 | 34.55 (34.2, 34.88) | 34.75 (33.9, 34.98) | 34.20 (33.9, 34.55) | 0.468 |
Platelets (×103 cells/μL) | 100–600 | 143.50 (135.5, 152.5) | 150.50 (137.25, 164.75) | 139.00 (131.25, 173) | 0.975 |
WBC (×103 cells/μL) | 5.50–12.0 | 7.26 (6.97, 7.54) A | 4.89 (4.38, 4.99) B | 6.78 (4.95, 7.52) A | <0.001 * |
Neutrophils (×103 cells/μL) | 3.00–7.00 | 3.84 (3.4, 4.56) | 3.12 (2.7, 3.44) | 3.81 (2.56, 4.32) | 0.112 |
Lymphocytes (×103 cells/μL) | 1.50–5.00 | 2.45 (2.01, 3.23) A | 1.44 (1.29, 1.54) B | 2.11 (1.86, 2.3) A | <0.001 * |
Monocytes (×103 cells/μL) | 0.00–1.00 | 0.38 (0.35, 0.38) A | 0.23 (0.17, 0.25) B | 0.31 (0.29, 0.41) A | 0.005 * |
Eosinophils (×103 cells/μL) | 0.00–1.00 | 0.13 (0.13, 0.22) | 0.08 (0.05, 0.01) | 0.11 (0.08, 0.15) | 0.262 |
Basophils (×103 cells/μL) | 0.00–2.00 | 0.03 (0.03, 0.05) | 0.02 (0.01, 0.02) | 0.03 (0.02, 0.04) | 0.123 |
T0 | T1 | T2 | p-Value | |
---|---|---|---|---|
VOLStandard (L) | 11.3 (9.725, 12.425) a | 16.9 (14.925, 17.875) b | 15.150 (12.425, 16.425) a,b | 0.032 * |
VOLModified (L) | 7.8 (7.025, 9.2) a | 13.3 (11.98, 14.15) b | 10.7 (8.6, 12.2 a,b | 0.045 * |
REF | T0 | T1 | T2 | p-Value | |
---|---|---|---|---|---|
CT (s) | 536–1270 | 756 (750, 783) | 788 (741, 1053) | 849 (828, 882) | 0.21 |
CFT (s) | 123–574 | 284 (266, 347) | 347 (291, 377) | 318.5 (309, 378) | 0.33 |
Alpha (deg) | 12–51 | 35.5 (33, 40) | 32.5 (26, 34) | 34.5 (27, 37) | 0.097 |
A10 (VCM units) | 9–27 | 19 (17, 20) | 20.5 (16, 24) | 18 (17, 19) | 0.75 |
A20 (VCM units) | 18–36 | 24 (21, 26) | 29 (27, 33) | 27 (24, 30) | 0.068 |
MCF (VCM units) | 17–39 | 24 (21, 26) a | 31 (28, 34) b | 28 (25, 31) a,b | 0.044 * |
LI30 (%) | 97–100 | 100 (100, 100) | 100 (100, 100) | 100 (100, 100) | 0.91 |
LI45 (%) | 82–100 | 95 (91, 96) | 96 (94, 96) | 95 (91, 96) | 0.399 |
Fibrinogen (mg/dL) | 103–254 | 163 (145, 177) | 151 (141, 169) | 142 (124, 157) | 0.213 |
PT (s) | 8–15 | 11 (11, 12) | 11 (11, 12) | 12 (12, 12) | 0.178 |
PTT (s) | 33–47 | 31 (30, 33) a | 30 (28, 30) b | 32 (32, 33) a | 0.024 * |
Platelets (×103 cells/μL) | 100–600 | 144 (136, 153) | 151 (137, 165) | 139 (131, 173) | 0.975 |
1000 ng/mL | 500 ng/mL | 250 ng/mL | 125 ng/mL | 62.5 ng/mL | 0 ng/mL | Conc | Horse | |
---|---|---|---|---|---|---|---|---|
CT (s) | 974 (884, 1056) | 900 (849, 910) | 850 (837, 982) | 877 (790, 984) | 809 (806, 886) | 908 (778, 977) | 0.207 | <0.001 * |
CFT (s) | 381 (350, 428) | 287 (234, 326) | 351 (318, 425) | 380 (317, 447) | 363 (319, 410) | 276 (212, 437) | 0.972 | 0.023 * |
Alpha (deg) | 31.5 (26, 37) | 35 (32, 39) | 36 (31, 37) | 31 (29, 34) | 31 (30, 34) | 40 (29, 48) | 0.3 | <0.001 * |
A10 (VCM units) | 14.5 (13, 16) | 19 (18, 20) | 14 (13, 17) | 14 (13 17) | 17 (15, 19) | 22 (17, 24) | 0.452 | 0.158 |
A20 (VCM units) | 20 (18, 22) | 25 (24, 27) | 18 (18, 22) | 18 (17, 21) | 22 (20, 24) | 28 (24, 28) | 0.654 | 0.094 |
MCF (VCM units) | 20 (19, 24) | 25 (24, 27) | 18 (18, 22) | 19 (17, 22) | 23 (21, 24) | 28 (24, 28) | 0.891 | 0.297 |
LI30 (%) | 100 (94, 100) | 100 (99, 100) | 100 (100, 100) | 100 (100, 100) | 100 (100, 100) | 100 (100, 100) | 0.063 | 0.329 |
LI45 (%) | 94 (94, 94) | 93 (93, 93) | 94 (94, 94) | 95 (94, 96) | 94 (93, 97) | 92 (89, 94) | 1 | 0.238 |
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Mersich, I.; Bishop, R.C.; Diaz Yucupicio, S.; Nobrega, A.D.; Austin, S.M.; Barger, A.M.; Fick, M.E.; Wilkins, P.A. Decreased Circulating Red Cell Mass Induced by Intravenous Acepromazine Administration Alters Viscoelastic and Traditional Plasma Coagulation Testing Results in Healthy Horses. Animals 2024, 14, 3102. https://doi.org/10.3390/ani14213102
Mersich I, Bishop RC, Diaz Yucupicio S, Nobrega AD, Austin SM, Barger AM, Fick ME, Wilkins PA. Decreased Circulating Red Cell Mass Induced by Intravenous Acepromazine Administration Alters Viscoelastic and Traditional Plasma Coagulation Testing Results in Healthy Horses. Animals. 2024; 14(21):3102. https://doi.org/10.3390/ani14213102
Chicago/Turabian StyleMersich, Ina, Rebecca C. Bishop, Sandra Diaz Yucupicio, Ana D. Nobrega, Scott M. Austin, Anne M. Barger, Meghan E. Fick, and Pamela Anne Wilkins. 2024. "Decreased Circulating Red Cell Mass Induced by Intravenous Acepromazine Administration Alters Viscoelastic and Traditional Plasma Coagulation Testing Results in Healthy Horses" Animals 14, no. 21: 3102. https://doi.org/10.3390/ani14213102