title: Anticoagulation of juvenile sheep and goats with heparin, warfarin, and clopidogrel.
abstract: Little data exist on anticoagulation of young sheep and goats. We tested the effect of heparin, warfarin, and clopidogrel in two sheep and two goats weighing 17-35 kg. Each animal received heparin boluses of 80, 100, and 200 units/kg; goats also received 300, 350, and 400 units/kg. All animals received continuous heparin 40, 60, and 80 units/kg/hour; oral warfarin 0.3, 0.6, and 0.9 mg/kg/day; and oral clopidogrel 75 and 150 mg/day (2.8-3.4 and 5.6-6.9 mg/kg/day). Results were in the form of complete blood counts, activated clotting times (ACT), partial thromboplastin times, prothrombin times, thromboelastograms, and whole-blood lumiaggregometry. After heparin boluses of 200 units/kg, sheep and goats reached mean peak ACTs over 400 seconds. After continuous infusions of 40, 60 and 80 units/kg/hour, sheep and goats exceeded our therapeutic range for ACTs (195-215 seconds for sheep, 155-175 seconds for goats). For warfarin therapy, both sheep and goats required treatment with >0.6 mg/kg/day to achieve INRs over 2.5. Clopidogrel treatment, after 14-17 days of 75-150 mg/day, inhibited sheep platelets by 25-36% and goat platelets by 35-46%. We conclude that young sheep and goats can be safely and effectively anticoagulated with heparin and warfarin, and can also show a modest antiplatelet response to clopidogrel. Doses for each drug were generally higher than those used for humans, and warfarin therapy in sheep may be unpredictable. These results should be useful for developing anticoagulation protocols to test pediatric mechanical circulatory support devices.
authors.affiliation: Division of Artificial Organs, Department of Surgery, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Connell
authors.forename: Tigran
authors.initials: T
authors.lastname: Khalapyan
authors.forename: Hamid A
authors.initials: HA
authors.lastname: Al-Mondhiry
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Wilson
authors.forename: Gerson
authors.initials: G
authors.lastname: Rosenberg
authors.forename: William J
authors.initials: WJ
authors.lastname: Weiss
mesh_terms: D000367:Age Factors; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D005260:Female; D006041:Goats; D006493:Heparin / Q000494:pharmacology*; D008297:Male; D010314:Partial Thromboplastin Time; D010974:Platelet Aggregation / Q000187:drug effects; D011517:Prothrombin Time; D012756:Sheep; D013916:Thrombelastography; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014859:Warfarin / Q000494:pharmacology*; D014914:Whole Blood Coagulation Time
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D006493:Heparin; D000077144:Clopidogrel; D013988:Ticlopidine