Inhibition of platelet function with clopidogrel,as measured with a novel whole blood impedance aggregometer in horses |
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| Affiliation: | 1. Equine Clinic, Internal Medicine, Department of Veterinary Clinical Sciences, Justus-Liebig-University, Frankfurter Str. 126, 35392 Giessen, Germany;2. Unit for Biomathematics and Data Processing, Justus-Liebig-University, Frankfurter Str. 95, 35392 Giessen, Germany;3. Clinical Pathophysiology and Veterinary Clinical Pathology, Department of Veterinary Clinical Sciences, Justus-Liebig-University, Frankfurter Str. 126, 35392 Giessen, Germany;1. Division of Transfusion Medicine, Department of Laboratory Medicine, The Keenan Research Centre for Biomedical Science of St. Michael''s Hospital, Toronto, ON, Canada;2. Toronto Platelet Immunobiology Group, Toronto, ON, Canada;3. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada;4. Department of Medicine, University of Toronto, Toronto, ON, Canada;5. Department of Physics, Ryerson University, Toronto, ON, Canada;1. Faculty of Agricultural Sciences, University of Camagüey, Ignacio Agramonte Loynáz. Cuba. Carretera de Circunvalación Km 5 1/2, Camagüey 74 650, Cuba;2. Department of Veterinary Medicine, Federal University of Parana, Rua dos Funcionários, 1540 - Laboratório de Doenças Parasitárias, HV Juvevê, 80035-050 Curitiba, PR, Brasil;3. Department of Veterinary Science, University of Kentucky, Gluck Equine Research Center, Lexington, KY 40546-0099, USA;1. Département Hospitalo-Universitaire (I2B), UPMC Univ Paris 6, UMR 7211, F-75013 Paris, France;2. CNRS Centre National de la Recherche Scientifique, UMR 7211, F-75013 Paris, France;3. INSERM, UMRS959, F-75013 Paris, France;4. Department of Biotherapy, Groupe Hospitalier Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris 6, F-75013 Paris, France;5. Department of Immunology, Groupe Hospitalier Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris 6, F-75013 Paris, France;6. Department of Internal Medicine, Groupe Hospitalier Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris 6, F-75013 Paris, France |
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| Abstract: | This study aimed to validate a loading and maintenance clopidogrel dosing scheme for the inhibition of platelet function, measured by whole blood impedance aggregometry in healthy adult horses. Ten Warmblood horses received oral clopidogrel once daily. Doses were based on 50 kg weight categories and resulted in one loading dose of 6–6.5 mg/kg bodyweight and maintenance doses of 1.2–1.4 mg/kg over the next 4 days. Platelet function was measured via whole blood multiple electrode impedance aggregometry prior to (T0) and at 6, 12, 24, 48, 72, 96, 144, 192 and 240 h following the loading dose. Aggregometries for collagen (COLtest), arachidonic acid (ASPItest), adenosine diphosphate (ADPtest) and ADP with prostaglandin E1 (ADPtestHS) were performed. Statistical analyses included one way repeated measures ANOVAs and subsequent Dunnett's tests.Platelet aggregation induced by collagen remained unchanged. There were significant inhibitions in the ASPItest (P <0.01 at 192 h, and P <0.05 at 240 h) and the ADPtest and ADPtestHS (P < 0.01, with the exception of 240 h). The loading dose of clopidogrel induced rapid inhibition of platelet function within hours, and the low dose was suitable for maintaining the inhibition over the 4 days of therapy. Recovery of platelet function was restored 6 days after the cessation of medication, determined with the ADPtest and ADPtestHS, but remained inhibited with the ASPItest. The prolonged effect of clopidogrel may indicate differences in the activation of platelets between horses and humans that were previously unknown. |
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