• 1. Eikelboom JW, Anand SS, Malmberg K, et al. Unfractionated heparin and low-molecular-weight-heparin in acute coronary syndrome without ST elevation: a meta-analysis. Lancet 2000; 355: 19361942.

    • Search Google Scholar
    • Export Citation
  • 2. Quinlan DJ, McQuillan A, Eikelboom JW. Low-molecular-weight heparin compared with intravenous unfractionated heparin for treatment of pulmonary embolism: a meta-analysis of randomized, controlled trials. Ann Intern Med 2004; 140: 175183.

    • Search Google Scholar
    • Export Citation
  • 3. Garcia DA, Baglin TP, Weitz JI, et al. Parenteral anticoagulants: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (suppl 2): e24Se43S.

    • Search Google Scholar
    • Export Citation
  • 4. Hirsh J, Bauer KA, Donati MB, et al. Parenteral anticoagulations: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest 2008; 133: 141159.

    • Search Google Scholar
    • Export Citation
  • 5. Bara L, Samama M. Pharmacokinetics of low molecular weight heparins. Acta Chir Scand Suppl 1988; 543: 6572.

  • 6. Rodriguez DB, Harpster NK. Aortic thromboembolism associated with feline hypertrophic cardiomyopathy. Compend Contin Educ Pract Vet 2002; 24: 478482.

    • Search Google Scholar
    • Export Citation
  • 7. Smith CE, Rozanski EA, Freeman LM, et al. Use of low molecular weight heparin in cats: 57 (1999–2003). J Am Vet Med Assoc 2004; 225: 12371241.

    • Search Google Scholar
    • Export Citation
  • 8. Alwood AJ, Downend AD, Brooks MB, et al. Anticoagulant effects of low-molecular-weight heparins in healthy cats. J Vet Intern Med 2007; 21: 378387.

    • Search Google Scholar
    • Export Citation
  • 9. Van De Wiele CM, Hogan DF, Green HW, et al. Antithrombotic effect of enoxaparin in clinically healthy cats: a venous stasis model. J Vet Intern Med 2010; 24: 185191.

    • Search Google Scholar
    • Export Citation
  • 10. Vargo CL, Taylor SM, Carr A, et al. The effect of a low molecular weight heparin on coagulation parameters in healthy cats. Can J Vet Res 2009; 73: 132136.

    • Search Google Scholar
    • Export Citation
  • 11. Mischke R, Schmitt J, Wolken S, et al. Pharmacokinetics of the low molecular weight heparin dalteparin in cats. Vet J 2012; 192: 299303.

    • Search Google Scholar
    • Export Citation
  • 12. Harenberg J. Is laboratory monitoring of low-molecular-weight heparin therapy necessary? Yes. J Thromb Haemost 2004; 2: 547550.

  • 13. Bounameaux H, De Moerloose P. Is laboratory monitoring of low-molecular-weight heparin necessary? No. J Thromb Haemost 2004; 2: 551554.

    • Search Google Scholar
    • Export Citation
  • 14. Fareed J, Walenga JM, Kumar A, et al. A modified stasis thrombosis model to study the antithrombotic actions of heparin and its fractions. Semin Thromb Hemost 1985; 11: 155175.

    • Search Google Scholar
    • Export Citation
  • 15. Heilmann L, Rath W, Pollow K, et al. The rheological changes after cesarean section: the influence of low molecular weight or unfractionated heparin on the rheological properties of blood. Clin Hemorheol Microcirc 2007; 37: 211218.

    • Search Google Scholar
    • Export Citation
  • 16. Berresheim M, Wilkie J, Nerenberg KA, et al. A case series of LMWH use in pregnancy: should trough anti-Xa levels guide dosing? Thromb Res 2014; 134: 12341240.

    • Search Google Scholar
    • Export Citation
  • 17. Kaul S, Shah PK. Low molecular weight heparin in acute coronary syndrome: evidence for superior or equivalent efficacy compared with unfractionated heparin? J Am Coll Cardiol 2000; 35: 16991712.

    • Search Google Scholar
    • Export Citation
  • 18. Verstraete M. Pharmacotherapeutic aspects of unfractionated and low molecular weight heparins. Drugs 1990; 40: 498530.

  • 19. Middeldorp S. Heparin: from animal organ extract to designer drug. Thromb Res 2008; 122: 753762.

  • 20. Boneu B. Low molecular weight heparin therapy: is monitoring needed? Thromb Haemost 1994; 72: 330334.

  • 21. Fareed J, Jeske W, Hoppensteadt D, et al. Low-molecular-weight heparins: pharmacologic profile and product differentiation. Am J Cardiol 1998; 82: 3L10L.

    • Search Google Scholar
    • Export Citation
  • 22. White H, Sosnowski K, Bird R, et al. The utility of thromboelastography in monitoring low molecular weight heparin therapy in the coronary care unit. Blood Coagul Fibrinolysis 2012; 23: 304310.

    • Search Google Scholar
    • Export Citation
  • 23. Brainard BM, Koenig A, Babski DM, et al. Viscoelastic pharmacodynamics after dalteparin administration to healthy dogs. Am J Vet Res 2012; 73: 15771582.

    • Search Google Scholar
    • Export Citation
  • 24. Klein SM, Slaughter TF, Vail PT, et al. Thromboelastography as a perioperative measure of anticoagulation resulting from low molecular weight heparin: a comparison with anti-Xa concentrations. Anesth Analg 2000; 91: 10911095.

    • Search Google Scholar
    • Export Citation
  • 25. Artang R, Frandsen NJ, Nielsen JD. Application of basic and composite thrombelastography parameters in monitoring of the antithrombotic effect of the low molecular weight heparin dalteparin: an in vivo study. Thromb J 2009; 7: 14.

    • Search Google Scholar
    • Export Citation
  • 26. Brooks AC, Guillaumin J, Cooper ES, et al. Effects of hematocrit and red cell-independent viscosity on canine thromboelastographic tracings. Transfusion 2014; 54: 727734.

    • Search Google Scholar
    • Export Citation
  • 27. Smith SA, McMichael MA, Gilor S, et al. Correlation of hematocrit, platelet concentration, and plasma coagulation factors with results of thromboelastometry in canine whole blood samples. Am J Vet Res 2012; 73: 789798.

    • Search Google Scholar
    • Export Citation
  • 28. Hammerstingl C. Monitoring therapeutic anticoagulation with low molecular weight heparins: Is it useful or misleading? Cardiovasc Hematol Agents Med Chem 2008; 6: 282286.

    • Search Google Scholar
    • Export Citation
  • 29. Lunsford KV, Mackin AJ. Thromboembolic therapies in dogs and cats: an evidence-based approach. Vet Clin North Am Small Anim Pract 2007; 37: 579609.

    • Search Google Scholar
    • Export Citation
  • 30. Aguilar OM, Kleiman NS. Low molecular weight heparins. Expert Opin Pharmacother 2000; 1: 10911103.

  • 31. Hirsh J, Raschke R. Heparin and low-molecular-weight heparin: the seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest 2004; 126: 188S203S.

    • Search Google Scholar
    • Export Citation
  • 32. Levine MN, Raskob G, Beyth RJ, et al. Hemorrhagic complications of anticoagulant treatment; the seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest 2004;126 (suppl 3):287S–310S.

    • Search Google Scholar
    • Export Citation
  • 33. Lulic-Botica M, Raipurkar M, Sabo C, et al. Fluctuations of anti-Xa concentrations during maintenance enoxaparin therapy for neonatal thrombosis. Acta Paediatr 2012;101:e147–e150.

    • Search Google Scholar
    • Export Citation
  • 34. Hansen JB, Sandset PM. Differential effects of low molecular weight heparin and unfractionated heparin on circulating levels of antithrombin and tissue factor pathway inhibitor (TFPI): a possible mechanism for difference in therapeutic efficacy. Thromb Res 1998; 91: 177181.

    • Search Google Scholar
    • Export Citation
  • 35. Morris TA, Jacobson A, Marsh JJ, et al. Pharmacokinetics of UH and LMWH are similar with respect to antithrombin activity. Thromb Res 2005; 115: 4551.

    • Search Google Scholar
    • Export Citation
  • 36. Junqueira DRG. American College of Chest Physicians guidelines for heparin-induced thrombocytopenia: a need for evidence-based assessment of the baseline risk of heparin-induced thrombocytopenia. Chest 2013; 143: 11901191.

    • Search Google Scholar
    • Export Citation
  • 37. Mischke R, Grebe S, Jacobs C, et al. Amidolytic heparin activity and values for several hemostatic variables after repeated subcutaneous administration of high doses of a low molecular weight heparin in healthy dogs. Am J Vet Res 2001; 62: 595598.

    • Search Google Scholar
    • Export Citation

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Assessment of the effects of dalteparin on coagulation variables and determination of a treatment schedule for use in cats

Jette C. Schönig Dr Med Vet1 and Reinhard H. Mischke Prof Dr Med Vet2
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  • 1 Small Animal Clinic, University of Veterinary Medicine, Bünteweg 9, D-30559 Hannover, Germany.
  • | 2 Small Animal Clinic, University of Veterinary Medicine, Bünteweg 9, D-30559 Hannover, Germany.

Abstract

OBJECTIVE To determine a treatment protocol for SC administration of dalteparin to cats on the basis of currently available detailed pharmacokinetic data and to assess the effect of SC administration of dalteparin to cats on coagulation variables such as activated partial thromboplastin time (aPTT), thrombin time, and results for thromboelastometry, compared with effects on anti–activated coagulation factor X (anti-Xa) activity.

ANIMALS 6 healthy domestic shorthair cats.

PROCEDURES Cats received 14 injections of dalteparin (75 anti-Xa U/kg, SC) at 6-hour intervals. Blood samples were collected before and 2 hours after the first and second injections on days 1, 2, and 4. Anti-Xa activity was measured by use of a chromogenic substrate assay, aPTT and thrombin time were measured by use of an automated coagulometer, and viscoelastic measurements were obtained with thromboelastrometry.

RESULTS 2 hours after the second injection, the target peak anti-Xa activity range of 0.5 to 1.0 U/mL was achieved in all cats, whereas median trough values remained below this range. Peak anti-Xa activity had only minimal effects on coagulation variables; the maximum median ratio for aPTT (in relationship to the value before the first dalteparin injection) was 1.23.

CONCLUSIONS AND CLINICAL RELEVANCE Results of this study indicated that this treatment protocol resulted in reproducible anti-Xa activity in cats that was mostly within the targeted peak range of anti-Xa activity recommended for humans. Treatment in accordance with this protocol may not require routine coagulation monitoring of cats, but this must be confirmed in feline patients.

Contributor Notes

Address correspondence to Dr. Mischke (Reinhard.Mischke@tiho-hannover.de).

Dr. Schönig's present address is Tierarztpraxis Dr. Blöcker, Bahrenfelder Chaussee 4, D-22761 Hamburg, Germany.