Anticoagulation therapy in animal research

Abstract

Cornell College of Veterinary Medicine has published guidelines for dose evaluation on the Comparative Coagulation Heparin Site7. This site recommends extrapolation from human doses of heparin using a range from 200–300 U/kg/24 hr to a high dose of 400–800 U/kg/24 hr for unfractionated heparin and a dose of 2,000–5,000 U/adult human per 24-hrs when using low molecular weight heparin, with routine monitoring to attain a value of 1.5–2x the baseline activated clotting time (ACT). The comparatively more modern inclusion of antiplatelet therapy for long-term use, between weeks and months after a procedure, has been dominated in laboratory research by Clopidogrel. In general, Clopidogrel is combined with baby aspirin in dosages extrapolated from common human dose recommendations. For chronic dual antiplatelet therapy, recent research publications almost uniformly cite the use of 81 mg aspirin plus 75 mg Clopidogrel for animals in the 70 kg weight range8. For larger animals, the dose of aspirin is adjusted while keeping Clopidogrel at 75 mg for animals between 75 and 100 kg, depending on ACT. Published doses of aspirin are 0.5–1 mg/kg9. Although these regimens are in general use among the laboratory animal research support community, commonly utilized laboratory animal species—or in some cases, even strains—have variable inherent thrombogenicity and responsiveness to anticoagulants; they can be challenging to anticoagulate and delicate to titrate to the desirable state of thromboresistence without causing hemorrhage. Some evidence also suggests that diet may contribute to variability of response to anticoagulation therapy10. In a review of animal models for vascular conduits (vascular grafts, dialysis grafts), Byrom et al. discuss relative thrombogenicity of most of the conventionally utilized research models, finding sheep and small ruminants more difficult to anticoagulate than other species11. tion while other anticoagulants have their major effect at clotting co-factors. Some are specifically targeted at thrombin formation. The various anticoagulant classes are generally categorized as Vitamin K inhibitors (Coumadins and indandiones), Factor Xa inhibitors, low and high molecular weight heparins, thrombin inhibitors, and P2Y12 receptor antagonists. Aspirin (salicylic acid) continues to be a mainstay of antiplatelet therapy. Although an ever increasing array of new products for clot inhibition is marketed to physicians and often extrapolated into the veterinary market, for the most part the laboratory animal community relies heavily on heparins, the pioneer antiplatelet medication Plavix® (Clopidogrel; Bristol-Meyers Squibb, Bridgewater, NJ), and aspirin. Heparins include the commonly utilized short-acting unfractionated form and also newer, low molecular weight forms that have a longer half-life and are making their way into the research setting6. Common anticoagulants in today’s research facilities are listed in Table 1.

DOI: 10.1038/laban.1133

Cite this paper

@article{Hampshire2016AnticoagulationTI, title={Anticoagulation therapy in animal research}, author={Victoria A Hampshire}, journal={Lab Animal}, year={2016}, volume={45}, pages={431-432} }