Warfarin is an anticoagulant medication that has been studied for its effects and potential applications in equine medicine. It functions by inhibiting the synthesis of vitamin K-dependent clotting factors, which are essential for blood coagulation. In horses, warfarin has been explored for its role in managing thromboembolic disorders and for its potential impact on blood clot prevention. The pharmacokinetics and safety profile of warfarin in equines are subjects of ongoing research, as horses metabolize drugs differently than humans and other animals. This page compiles peer-reviewed research studies and scholarly articles that investigate the pharmacological properties, therapeutic uses, and safety considerations of warfarin in horses.
Mosher CM, Court MH.Pharmacogenomics is the study of the impact of genetic variation on drug effects, with the ultimate goal of achieving "personalised medicine". Since the completion of the Human Genome Project, great strides have been made towards the goal of personalised dosing of drugs in people, as exemplified by the development of gene-guided dosing of the anticoagulant drug, warfarin. Although the pharmacogenomics of domestic animals is still at an early stage of development, there is great potential for advances in the coming years as the direct result of complete genome sequences currently being derived ...
Wilson CR, Sauer JM, Carlson GP, Wallin R, Ward MP, Hooser SB.A comparative study of vitamin K(1) 2,3-epoxide reductase (VKOR) activity in vitro was conducted across species. The apparent kinetic constants K(m app), V(max), and Cl(int app) were determined in bovine, canine, equine, human, murine, ovine, porcine, and rat hepatic microsomes. In addition to these enzyme kinetic constants, the IC(50) of warfarin for VKOR was determined in human, murine, porcine, and rat hepatic microsomes. Interspecies differences were observed when comparing the K(m app) (range, 2.41-6.46 microM), V(max) (range, 19.5-85.7 nmol/mg/min), and Cl(int app) (range, 8.2-18.4 ml/mg...
Panjehshahin MR, Yates MS, Bowmer CJ.The fluorescent probes warfarin and dansylsarcosine are known to selectively interact with binding sites I and II, respectively, on human albumin. This paper investigates whether similar binding sites exist on bovine, dog, horse, sheep and rat albumins. Binding sites on albumins were studied by: (1) displacement of warfarin and dansylsarcosine by site I (phenylbutazone) and site II (diazepam) selective ligands; (2) the effects of non-esterified fatty acids (carbon chain lengths: C5-C20) and changes in pH (6-9) on the fluorescence of warfarin and dansylsarcosine; and (3) the ability of site sel...
Pause B, Nolte I, Geiss V, Mayer H, Lasch HG.A thoroughbred horse, suffering from intermittent lameness was treated with streptokinase, urokinase and warfarin. The appearing fibrinolytic changes in coagulation were exhibited in a resonance thrombogram. In attendant coagulation studies fibrinogen- and fibrin-degradation products were demonstrated. The stallion does not show any lameness since the end of the treatment and is standing in a breeding station since March 1988.
Byars TD, Greene CE, Kemp DT.Warfarin-induced anticoagulation and reversal of the induced anticoagulation by vitamin K1 were evaluated in 4 mature horses. Each horse was given warfarin IV until the prothrombin (PT) time was prolonged by approximately 1.5 times the predosing base-line value. In experiment 1, we evaluated the time required for PT to return to the predosing value (PT reversal time) after warfarin administration was discontinued. Between each experiment, a 1-week rest period was allowed. In experiment 2, two doses of vitamin K1 (100 mg/dose) were administered IM 6 hours apart, and the PT was monitored hourly ...
Amin TM, Sirs JA, Allen BV, Colles CM.A preliminary investigation has been undertaken of blood rheology in horses and ponies, its variation in navicular disease and the changes following treatment with warfarin. Erythrocyte flexibility, measured by a centrifuge packing technique, is higher in horses (30 per cent min-1) than in ponies (23.8 per cent min-1). There are corresponding differences in blood viscosity. The high erythrocyte flexibility in horses is caused by an unknown factor present in plasma. The erythrocyte flexibility in horses with navicular disease is even higher, at 38.5 per cent min-1. Treatment with warfarin reduc...
van den Bogaard AE, Thijssen HH, Hemker HC.The anticoagulant, warfarin, has been reported to be effective as treatment for navicular disease in horses. Since other forms of treatment for this disease are palliative, this new anticoagulant therapy has become widely employed. Despite the fact that initiation of anticoagulant therapy is relatively simple, attending veterinary practitioners should be aware that careful monitoring of this therapy is required for both safety and efficacy. Navicular disease is an example of equine thrombotic disease, and the goal of warfarin therapy is the prevention of new thrombus formation, while at the sa...
Vrins A, Carlson G, Feldman B.Warfarin or dicoumarol prevents the production of functional clotting factors II, VII, IX and X. Navicular disease and thrombophlebitis are examples of equine thrombotic diseases in which warfarin has been used therapeutically. The initiation of anticoagulant therapy is relatively simple but attending veterinarians must be aware of the potential risks in order to minimize them. These risks include epistaxis, bleeding into the gastrointestinal tract and at the venipuncture site, and increased susceptibility to hematoma formation following local trauma. Vitamin K, especially vitamin K(1) is a sw...
Vermeer C, Ulrich M.The presence of vitamin K-dependent carboxylase is demonstrated in the microsomal fraction of horse liver, spleen and kidney. The carboxylating enzyme systems in the spleen and in the kidney are susceptible to warfarin in a similar way as is carboxylase from the liver. It is concluded, that during the administration of vitamin K-antagonists (anticoagulation therapy) carboxylase in all these tissues is inhibited. Since most probably the majority of the reaction products of spleen and kidney carboxylase are no clotting factors, the inhibition of their production is a side-effect of the anticoagu...
Scott EA, Byars TD, Lamar AM.The hematologic and clinical effects of anticoagulation with warfarin were documented in 4 horses. All of the animals had thrombophlebitis (external jugular vein). Measures of coagulation were monitored, with a prothrombin time of 1.5 to 2.5 x base-line value being used as the effective range of anticoagulation. Recanalization was achieved in 2 of 4 cases. Hemorrhage, both subcutaneous and through a surgical incision, was a complication. Vitamin K1, an antidote to warfarin toxicosis, was administered intravenously to reverse anticoagulation and to control hemorrhage.
Colles CM.Twenty horses suffering from navicular disease were treated with warfarin given orally. The dosage was to effect, to give a 2 to 4 second prolongation of the one stage prothrombin time (OSPT). Dosage was initially at a rate of 0.018 mg/kg, changing the dose by amounts of 20 per cent until the required dose was achieved. Final dose rates varied from 0.012 mg/kg to 0.75 mg/kg. All the cases treated received warfarin daily throughout the trial. Seventeen of the animals became sound and the remaining 3 showed a marked improvement in their gait. The mean of the ages of the horses was 7.5 years, the...
Mosher CM, Court MH.Pharmacogenomics is the study of the impact of genetic variation on drug effects, with the ultimate goal of achieving "personalised medicine". Since the completion of the Human Genome Project, great strides have been made towards the goal of personalised dosing of drugs in people, as exemplified by the development of gene-guided dosing of the anticoagulant drug, warfarin. Although the pharmacogenomics of domestic animals is still at an early stage of development, there is great potential for advances in the coming years as the direct result of complete genome sequences currently being derived ...
Colles CM.Twenty horses suffering from navicular disease were treated with warfarin given orally. The dosage was to effect, to give a 2 to 4 second prolongation of the one stage prothrombin time (OSPT). Dosage was initially at a rate of 0.018 mg/kg, changing the dose by amounts of 20 per cent until the required dose was achieved. Final dose rates varied from 0.012 mg/kg to 0.75 mg/kg. All the cases treated received warfarin daily throughout the trial. Seventeen of the animals became sound and the remaining 3 showed a marked improvement in their gait. The mean of the ages of the horses was 7.5 years, the...
Wilson CR, Sauer JM, Carlson GP, Wallin R, Ward MP, Hooser SB.A comparative study of vitamin K(1) 2,3-epoxide reductase (VKOR) activity in vitro was conducted across species. The apparent kinetic constants K(m app), V(max), and Cl(int app) were determined in bovine, canine, equine, human, murine, ovine, porcine, and rat hepatic microsomes. In addition to these enzyme kinetic constants, the IC(50) of warfarin for VKOR was determined in human, murine, porcine, and rat hepatic microsomes. Interspecies differences were observed when comparing the K(m app) (range, 2.41-6.46 microM), V(max) (range, 19.5-85.7 nmol/mg/min), and Cl(int app) (range, 8.2-18.4 ml/mg...
Scott EA, Byars TD, Lamar AM.The hematologic and clinical effects of anticoagulation with warfarin were documented in 4 horses. All of the animals had thrombophlebitis (external jugular vein). Measures of coagulation were monitored, with a prothrombin time of 1.5 to 2.5 x base-line value being used as the effective range of anticoagulation. Recanalization was achieved in 2 of 4 cases. Hemorrhage, both subcutaneous and through a surgical incision, was a complication. Vitamin K1, an antidote to warfarin toxicosis, was administered intravenously to reverse anticoagulation and to control hemorrhage.
Vrins A, Carlson G, Feldman B.Warfarin or dicoumarol prevents the production of functional clotting factors II, VII, IX and X. Navicular disease and thrombophlebitis are examples of equine thrombotic diseases in which warfarin has been used therapeutically. The initiation of anticoagulant therapy is relatively simple but attending veterinarians must be aware of the potential risks in order to minimize them. These risks include epistaxis, bleeding into the gastrointestinal tract and at the venipuncture site, and increased susceptibility to hematoma formation following local trauma. Vitamin K, especially vitamin K(1) is a sw...
Byars TD, Greene CE, Kemp DT.Warfarin-induced anticoagulation and reversal of the induced anticoagulation by vitamin K1 were evaluated in 4 mature horses. Each horse was given warfarin IV until the prothrombin (PT) time was prolonged by approximately 1.5 times the predosing base-line value. In experiment 1, we evaluated the time required for PT to return to the predosing value (PT reversal time) after warfarin administration was discontinued. Between each experiment, a 1-week rest period was allowed. In experiment 2, two doses of vitamin K1 (100 mg/dose) were administered IM 6 hours apart, and the PT was monitored hourly ...
Vermeer C, Ulrich M.The presence of vitamin K-dependent carboxylase is demonstrated in the microsomal fraction of horse liver, spleen and kidney. The carboxylating enzyme systems in the spleen and in the kidney are susceptible to warfarin in a similar way as is carboxylase from the liver. It is concluded, that during the administration of vitamin K-antagonists (anticoagulation therapy) carboxylase in all these tissues is inhibited. Since most probably the majority of the reaction products of spleen and kidney carboxylase are no clotting factors, the inhibition of their production is a side-effect of the anticoagu...
Amin TM, Sirs JA, Allen BV, Colles CM.A preliminary investigation has been undertaken of blood rheology in horses and ponies, its variation in navicular disease and the changes following treatment with warfarin. Erythrocyte flexibility, measured by a centrifuge packing technique, is higher in horses (30 per cent min-1) than in ponies (23.8 per cent min-1). There are corresponding differences in blood viscosity. The high erythrocyte flexibility in horses is caused by an unknown factor present in plasma. The erythrocyte flexibility in horses with navicular disease is even higher, at 38.5 per cent min-1. Treatment with warfarin reduc...
van den Bogaard AE, Thijssen HH, Hemker HC.The anticoagulant, warfarin, has been reported to be effective as treatment for navicular disease in horses. Since other forms of treatment for this disease are palliative, this new anticoagulant therapy has become widely employed. Despite the fact that initiation of anticoagulant therapy is relatively simple, attending veterinary practitioners should be aware that careful monitoring of this therapy is required for both safety and efficacy. Navicular disease is an example of equine thrombotic disease, and the goal of warfarin therapy is the prevention of new thrombus formation, while at the sa...
Pause B, Nolte I, Geiss V, Mayer H, Lasch HG.A thoroughbred horse, suffering from intermittent lameness was treated with streptokinase, urokinase and warfarin. The appearing fibrinolytic changes in coagulation were exhibited in a resonance thrombogram. In attendant coagulation studies fibrinogen- and fibrin-degradation products were demonstrated. The stallion does not show any lameness since the end of the treatment and is standing in a breeding station since March 1988.
Panjehshahin MR, Yates MS, Bowmer CJ.The fluorescent probes warfarin and dansylsarcosine are known to selectively interact with binding sites I and II, respectively, on human albumin. This paper investigates whether similar binding sites exist on bovine, dog, horse, sheep and rat albumins. Binding sites on albumins were studied by: (1) displacement of warfarin and dansylsarcosine by site I (phenylbutazone) and site II (diazepam) selective ligands; (2) the effects of non-esterified fatty acids (carbon chain lengths: C5-C20) and changes in pH (6-9) on the fluorescence of warfarin and dansylsarcosine; and (3) the ability of site sel...
