In vitro effects of three formulations of hydroxyethyl starch solutions on coagulation and platelet function in horses

April E. Blong Department of Clinical Sciences, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

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Kira L. Epstein Department of Clinical Sciences, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

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Benjamin M. Brainard Department of Clinical Sciences, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

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Abstract

Objective—To investigate the in vitro effects of 3 hydroxyethyl starch (HES) solutions on viscoelastic coagulation testing and platelet function in horses.

Sample—Blood samples collected from 7 healthy adult horses.

Procedures—Blood samples were diluted with various crystalloid and HES solutions to approximate the dilution of blood in vivo that occurs with administration of a 10 and 20 mL/kg fluid bolus to a horse (1:8 and 1:4 dilutions, respectively). Diluted samples were analyzed through optical platelet aggregometry, platelet function analysis, thromboelastography, and dynamic viscoelastic coagulometry. Colloid osmotic pressure and concentrations of von Willebrand factor and factor VIII:C were also determined for each sample.

Results—For all HES products, at both dilutions, the colloid osmotic pressure was significantly higher than that in the respective carrier solutions. At the 1:4 dilution, nearly all HES solutions resulted in significant alterations in platelet function as measured via the platelet function analyzer and dynamic viscoelastic coagulometer. Significant decreases in platelet aggregation and factor concentrations were also evident. Fewer HES-associated changes were identified at the 1:8 dilutions.

Conclusions and Clinical Relevance—Dilution of blood samples with all HES solutions resulted in changes in viscoelastic coagulation and platelet function that did not appear to be attributable to dilution alone. In vivo evaluations are necessary to understand the clinical impact of these in vitro changes.

Abstract

Objective—To investigate the in vitro effects of 3 hydroxyethyl starch (HES) solutions on viscoelastic coagulation testing and platelet function in horses.

Sample—Blood samples collected from 7 healthy adult horses.

Procedures—Blood samples were diluted with various crystalloid and HES solutions to approximate the dilution of blood in vivo that occurs with administration of a 10 and 20 mL/kg fluid bolus to a horse (1:8 and 1:4 dilutions, respectively). Diluted samples were analyzed through optical platelet aggregometry, platelet function analysis, thromboelastography, and dynamic viscoelastic coagulometry. Colloid osmotic pressure and concentrations of von Willebrand factor and factor VIII:C were also determined for each sample.

Results—For all HES products, at both dilutions, the colloid osmotic pressure was significantly higher than that in the respective carrier solutions. At the 1:4 dilution, nearly all HES solutions resulted in significant alterations in platelet function as measured via the platelet function analyzer and dynamic viscoelastic coagulometer. Significant decreases in platelet aggregation and factor concentrations were also evident. Fewer HES-associated changes were identified at the 1:8 dilutions.

Conclusions and Clinical Relevance—Dilution of blood samples with all HES solutions resulted in changes in viscoelastic coagulation and platelet function that did not appear to be attributable to dilution alone. In vivo evaluations are necessary to understand the clinical impact of these in vitro changes.

Contributor Notes

Dr. Blong's present address is Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.

Supported by the University of Georgia For the Love of the Horse Program. Voluven was provided by Abbott Animal Health.

Address correspondence to Dr. Blong (aeb287@cornell.edu).
  • 1. Jungheinrich C. The starch family: are they all equal? Pharmacokinetics and pharmacodynamics of hydroxyethyl starches. Transfus Altern Transfus Med 2007; 9:152163.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2. Jones PA, Tomasic M, Gentry PA. Oncotic, hemodilutional, and hemostatic effects of isotonic saline and hydroxyethyl starch solutions in clinically normal ponies. Am J Vet Res 1997; 58:541548.

    • Search Google Scholar
    • Export Citation
  • 3. Hallowell GD, Corely KT. Preoperative administration of hydroxyethyl starch or hypertonic saline to horses with colic. J Vet Intern Med 2006; 20:980986.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4. Pantaleon LG, Furr MO, McKenzie HC II, et al. Cardiovascular and pulmonary effects of hetastarch plus hypertonic saline solutions during experimental endoxtoxemia in anesthetized horses. J Vet Intern Med 2006; 20:14221428.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5. Jones PA, Bain FT, Byars TD, et al. Effects of hydroxyethyl starch infusion on colloid oncotic pressure in hypoproteinemic horses. J Am Vet Med Assoc 2001; 218:11301135.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6. Schusser GF, Reickhoff K, Ungemach FR, et al. Effect of hydroxyethyl starch solution in normal horses and horses with colic or acute colitis. J Vet Med A Physiol Pathol Clin Med 2007; 54:592598.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7. Cohen ND, Woods AM. Characteristics and risk factors for failure of horses with acute diarrhea to survive: 122 cases (1990–1996). J Am Vet Med Assoc 1999; 214:382390.

    • Search Google Scholar
    • Export Citation
  • 8. Pantaleon LG, Furr MO, McKenzie HC, et al. Effects of small- and large-volume resuscitation on coagulation and electrolytes during experimental endotoxemia in anesthetized horses. J Vet Intern Med 2007; 21:13741379.

    • Search Google Scholar
    • Export Citation
  • 9. Southwood LL, Dolente BA, Lindborg S, et al. Short-term outcome of equine emergency admissions at a university referral hospital. Equine Vet J 2009; 41:459464.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10. Kozek-Langenecker SA. Effects of hydroxyethyl starch solutions on hemostasis. Anesthesiology 2005; 103:654660.

  • 11. Westphal M, James MF, Kozek-Langenecker S, et al. Hydroxyethyl starches: different products—different effects. Anesthesiology 2009; 111:187202.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12. Martin G, Bennett-Guerrero E, Wakeling H, et al. A prospective, randomized comparison of thromboelastographic coagulation profile in patients receiving lactated Ringer's solution, 6% hetastarch in a balanced-saline vehicle, or 6% hetastarch in saline during major surgery. J Cardiothorac Vasc Anesth 2002; 16:441446.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13. Van der Linden P, Ickx B. The effects of colloid solutions on hemostasis. Can J Anaesth 2006; 53:S30S39.

  • 14. Wierenga JR, Jandrey KE, Haskins SC, et al. In vitro comparison of the effects of two forms of hydroxyethyl starch solutions on platelet function in dogs. Am J Vet Res 2007; 68:605609.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15. Smart L, Jandrey KE, Kass PH, et al. The effect of hetastarch (670/0.75) in vivo on platelet closure time in the dog. J Vet Emerg Crit Care (San Antonio) 2009; 19:444449.

    • Search Google Scholar
    • Export Citation
  • 16. Fenger-Eriksen C, Tonnesen E, Ingerslev J, et al. Mechanisms of hydroxyethyl starch-induced dilutional coagulopathy. J Thromb Haemost 2009; 7:10991105.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17. Franz A, Braunlich P, Gamsjager T, et al. The effects of hydroxyethyl starches of varying molecular weights on platelet function. Anesth Analg 2001; 92:14021407.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18. Frazer ML. Lawsonia intracellularis infection in horses: 2005–2007. J Vet Intern Med 2008; 22:12431248.

  • 19. Silverstein D, Aldrich J, Haskins S, et al. Assessment of changes in blood volume in response to resuscitative fluid administration in dogs. J Vet Emerg Crit Care 2005; 15:185192.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20. Strunden MS, Heckel K, Goetz AE, et al. Perioperative fluid and volume management: physiological basis, tools, and strategies. Ann Intensive Care 2011; 1:2.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21. Jungheinrich C, Neff TA. Pharmacokinetics of hydroxyethyl starch. Clin Pharmacokinet 2005; 44:681699.

  • 22. Dolente BA, Wilkins PA, Boston RC. Clinicopathologic evidence of disseminated intravascular coagulation in horses with acute colitis. J Am Vet Med Assoc 2002; 220:10341038.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23. Bentz AI, Palmer JE, Dallap BL, et al. Prospective evaluation of coagulation in critically ill neonatal foals. J Vet Intern Med 2009; 23:161167.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24. Dallap Schaer BL, Bentz AI, Boston RC, et al. Comparison of viscoelastic coagulation analysis and standard coagulation profiles in critically ill neonatal foals to outcome. J Vet Emerg Crit Care (San Antonio) 2009; 19:8895.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25. Epstein KL, Brainard BM, Lopes M, et al. Thrombelastography in 26 healthy horses with and without activation by recombinant human tissue factor. J Vet Emerg Crit Care (San Antonio) 2009; 19:96101.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26. Roberts DE, McNicol A, Bose R. Mechanism of collagen activation in human platelets. J Biol Chem 2004; 279:1942119430.

  • 27. Riewald M, Ruf W. Scientific review: role of coagulation protease cascades in sepsis. Crit Care 2003; 7:123129.

  • 28. Mateos-Trigos G, Evans R, Heath M. Effects of a P2Y(12) receptor antagonist on the response of equine platelets to ADP, comparison with human platelets. Res Vet Sci 2002; 73:171175.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29. Ganter MT, Hofer CK. Coagulation monitoring: current techniques and clinical use of viscoelastic point-of-care coagulation devices. Anesth Analg 2008; 106:13661375.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30. Casella S, Giudice E, Giannetto C, et al. Effects of hydrocortisone and aminophylline on the aggregation of equine platelets. J Vet Sci 2011; 12:215219.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31. Kingston JK, Bayly WM, Sellon DC, et al. Effects of sodium citrate, low molecular weight heparin, and prostaglandin E1 on aggregation, fibrinogen binding, and enumeration of equine platelets. Am J Vet Res 2001; 62:547554.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32. Reikvam H, Steien E, Hauge B, et al. Thrombelastography. Transfus Apheresis Sci 2009; 40:119123.

  • 33. Myers KM, Lindner C, Grant B. Characterization of the equine platelet aggregation response. Am J Vet Res 1979; 40:260264.

  • 34. Brainard BM, Epstein KL, LoBato D, et al. Effects of clopidogrel and aspirin on platelet aggregation, thromboxane production, and serotonin secretion in horses. J Vet Intern Med 2011;25:116122.

    • Search Google Scholar
    • Export Citation
  • 35. Brunso L, Segura D, Monreal L, et al. The secretory mechanisms in equine platelets are independent of cytoskeletal polymerization and occur through membrane fusion. Platelets 2010; 21:658666.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36. Norris JW, Pratt SM, Auh JH, et al. Investigation of a novel, heritable bleeding diathesis of Thoroughbred horses and development of a screening assay. J Vet Intern Med 2006; 20:14501456.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37. Textor JA, Norris JW, Tablin F. Effects of preparation method, shear force, and exposure to collagen on release of growth factors from equine platelet-rich plasma. Am J Vet Res 2011; 72:271278.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 38. Schaden E, Wetzel L, Kozek-Langenecker S, et al. Effect of the carrier solution for hydroxyethyl starch on platelet aggregation and clot formation. Br J Anaesth 2012; 109:572577.

    • Crossref
    • Search Google Scholar
    • Export Citation

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