Topic:Anticoagulants
Anticoagulants are substances that prevent blood clotting, used in equine medicine to manage conditions associated with thrombosis or abnormal coagulation. In horses, anticoagulants are employed to address issues such as laminitis, thrombophlebitis, and certain cardiovascular disorders. Common anticoagulants used in equine practice include heparin and warfarin, each with specific mechanisms of action and therapeutic applications. The administration of these agents requires careful monitoring due to potential side effects and the need for precise dosing. This entry aggregates peer-reviewed research studies and scholarly articles that explore the pharmacology, therapeutic use, and safety considerations of anticoagulants in equine health care.
The type of anticoagulant used for plasma collection affects in vitro Rhodococcus equi assays. The efficacy of Rhodococcus equi-specific hyperimmune plasma (HIP) is usually evaluated in vitro. Anticoagulants (AC) used for plasma collection can negatively impact bacterial replication but their effect on R. equi growth has not been evaluated. The aim of this study was to establish the effect that AC routinely used in veterinary medicine (ACD, KEDTA, Li Heparin, and Na Citrate) have on in vitro R. equi growth. To assess this, in vitro assays commonly used to test HIP efficacy (direct effect on microorganism and macrophage infection), were performed using each AC and non-treated bacteria. R...
Pharmacokinetics and Pharmacodynamics of an Oral Formulation of Apixaban in Horses After Oral and Intravenous Administration. Horses with inflammatory and infectious disorders are often treated with injectable heparin anticoagulants to prevent thrombotic complications. In humans, a new class of direct oral acting anticoagulants (DOAC) appear as effective as heparin, while eliminating the need for daily injections. Our study in horses evaluated apixaban, a newly approved DOAC for human thromboprophylaxis targeting activated factor X (Xa). Our goals were to: (1) Determine pharmacokinetics and pharmacodynamics of apixaban after oral (PO) and intravenous (IV) administration in horses; (2) Detect any inhibitory effects of...
Subcutaneous Administration of Low-Molecular-Weight Heparin to Horses Inhibits Ex Vivo Equine Herpesvirus Type 1-Induced Platelet Activation. Equine herpesvirus type 1 (EHV-1) is a major cause of infectious respiratory disease, abortion and neurologic disease. Thrombosis in placental and spinal vessels and subsequent ischemic injury in EHV-1-infected horses manifests clinically as abortion and myeloencephalopathy. We have previously shown that addition of heparin anticoagulants to equine platelet-rich plasma (PRP) can abolish ex vivo EHV-1-induced platelet activation. The goal of this study was to test whether platelets isolated from horses treated with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) were resista...
Suspected aspirin resistance in individual healthy adult warmblood horses. The reasons for this prospective experimental study were to determine a dosing scheme with loading and maintenance dose of aspirin inducing inhibition of platelet function measured by whole blood impedance aggregometry. Ten horses received aspirin orally in the morning with one loading dose of 4.7-5 mg/kg and maintenance doses of 1-1.3 mg/kg daily the following 4 days. Aggregometries (COLtest, ASPItest, ADPtest) and serum salicylic acid were measured. ASPItest showed significant difference in inhibition at 24 and 48 hr (p < .05) and 96 hr (p < .01). Significant change for ADPtes...
Unfractionated and Low-Molecular-Weight Heparin and the Phosphodiesterase Inhibitors, IBMX and Cilostazol, Block Ex Vivo Equid Herpesvirus Type-1-Induced Platelet Activation. Equid herpes virus type-1 (EHV-1) is a major pathogen of horses, causing abortion storms and outbreaks of herpes virus myeloencephalopathy. These clinical syndromes are partly attributed to ischemic injury from thrombosis in placental and spinal vessels. The mechanism of thrombosis in affected horses is unknown. We have previously shown that EHV-1 activates platelets through virus-associated tissue factor-initiated thrombin generation. Activated platelets participate in thrombus formation by providing a surface to localize coagulation factor complexes that amplify and propagate thrombin genera...
Evaluation of an oral direct factor Xa inhibitor anticoagulant in healthy adult horses. To assess whether an oral direct factor Xa inhibitor (DiXaI) anticoagulant drug used at the low end of the recommended dose in people achieves presumed prophylactic plasma concentrations and does not induce bleeding in horses. Methods: Experimental study. Methods: Field study. Methods: Ten healthy adult horses. Methods: A DiXaI was administered at a dose of 0.125 mg/kg every 24 h orally for 4 days. Following a wash-out period of 2 weeks, 8 of 10 horses received daily subcutaneous doses of a low molecular weight heparin (dalteparin) for 4 consecutive days at 50 IU/kg. In both trials, antifactor...
[Catheter-associated complications in the horse – diagnosis and treatment in practice]. Venous diseases due to venous catheters have variable symptoms and clinical progress. They comprise perivenous hematoma, periphlebitis, endophlebitis, phlebothrombosis or septic thrombophlebitis. To diagnose venous disease, a clinical examination (possibillity to distend the vein, swelling, pain, increased skin temperature, and any exudation around the injection site) and an ultrasonographic examination (perivenous tissue, venous wall, venous content) of the vein are performed. Treatment of venous diseases depends on the etiology and pathogenesis and combines the use of anticoagulants (heparin...
Effects of sodium citrate and acid citrate dextrose solutions on cell counts and growth factor release from equine pure-platelet rich plasma and pure-platelet rich gel. There is a lack information on the effects of the most commonly used anticoagulants for equine platelet rich plasmas (PRPs) elaboration on cell counts and growth factor release from platelet rich gels (PRGs). The aims of this study were 1) to compare the effects of the anticoagulants sodium citrate (SC), acid citrate dextrose solution A (ACD-A) and ACD-B on platelet (PLT), leukocyte (WBC) and on some parameters associated to platelet activation including mean platelet volume (MPV) and platelet distribution width (PDW) between whole blood, pure PRP (P-PRP) and platelet-poor plasma (PPP); 2) to ...
Cluster of cases of massive hemorrhage associated with anticoagulant detection in race horses. Five horses originating from 4 different California race tracks were submitted to the California Animal Health and Food Safety Laboratory for necropsy and diagnostic workup. The 5 horses had a history of sudden collapse and death during exercise. In all of them, massive hemoperitoneum and hemorrhages in other cavities or organs were observed. The liver from these 5 animals and from 27 horses that had been euthanized due to catastrophic leg injuries (controls) were subjected to a rodenticide anticoagulant screen. Traces of brodifacoum, diphacinone, or bromadiolone were detected in the 5 horses ...
Changes in platelet morphology and function during 24 hours of storage. For in vitro studies assessing the interaction of platelets with implant materials, common and standardized protocols for the preparation of platelet rich plasma (PRP) are lacking, which may lead to non-matching results due to the diversity of applied protocols. Particularly, the aging of platelets during prolonged preparation and storage times is discussed to lead to an underestimation of the material thrombogenicity. Here, we study the influence of whole blood- and PRP-storage times on changes in platelet morphology and function. Blood from apparently healthy subjects was collected according...
Bilateral internal carotid and vertebral artery dissection after a horse-riding injury. Blunt cerebrovascular injuries, defined as blunt injuries to the internal carotid or vertebral arteries, are uncommon and usually occur in victims of high-speed deceleration motor vehicle crashes. A blunt cerebrovascular injury after an equestrian accident is an extremely unusual presentation. In recent years, advances in screening and treatment with pharmacologic anticoagulation before the onset of neurologic symptoms have improved outcomes for these patients. Endovascular stenting and embolization, although unproven, offer a new potential approach for these complex injuries. We present a uni...
Comparative and veterinary pharmacogenomics. 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 ...
Plasma endotoxin concentration in horses: a methods study. Accurate determination of plasma endotoxin concentration is critical for ex vivo and in vitro cellular and molecular studies of endotoxemia in horses. However, reports are conflicting with respect to anticoagulant, handling, and sample preparation. Objective: The purpose of this study was to determine the effect of blood sample fraction and handling time on measurement of endotoxin concentration in horses. Methods: Whole blood, anticoagulated with 3.8% (0.12 M) sodium citrate (9:1), was collected from 5 healthy horses. Whole blood (WB), platelet-rich plasma (PRP), and platelet-poor plasma (PPP...
The effect of acetylsalicylic acid and captopril on uterine and ovarian blood flow during the estrous cycle in mares. In previous studies, transrectal color Doppler sonography was used to demonstrate an increase in genital blood flow resistance in subfertile mares. The objectives of the present study were to determine the effects of an anticoagulant (acetylsalicylic acid) and a vasodilator (captopril) on uterine and ovarian perfusion and plasma progesterone concentrations in cycling mares. From Day 1 to 11 of an estrous cycle (Day 0=day of ovulation following prostaglandin-induced luteolysis), five Trotter mares were given 2500 mg lactose, 2500 mg ASA, or 50 mg captopril twice daily in their feed (one compoun...
Comparison of pharmacokinetic variables for two low-molecular-weight heparins after subcutaneous administration of a single dose to horses. To determine pharmacokinetic variables and to evaluate the influence on clotting times after SC administration of single doses of dalteparin and enoxaparin to horses. Methods: 5 healthy adult horses. Methods: The study was designed as a 4-period crossover study. Each horse received a single SC injection of dalteparin (50 and 100 anti-Xa U/kg) and enoxaparin (40 and 80 anti-Xa U/kg). Plasma anti-Xa activities and clotting times were measured, and pharmacokinetic variables were determined. Absolute and relative maximal prolongation of clotting times was calculated, and correlation between plasma...
Reconstruction of the jugular vein in horses with post thrombophlebitis stenosis using saphenous vein graft. A surgical technique is described in which a saphenous vein graft is used to reconstruct the jugular vein in horses with facial oedema due to post thrombophlebitic stenosis of the jugular vein. The saphenous vein was harvested from the contralateral limb and implanted in the occluded vein by 2 side-to-end anastomoses. Intra- and post operatively anticoagulative medication was administered. In 2 out of 3 patients the reconstruction resulted in a permanent patent graft and resolution of the facial oedema. In one patient the graft thrombosed.
Assessment of the potential toxicity of a poison for rabbits, pindone (2-pivalyl 1, 3 indandione), to domestic animals. The toxicity of pindone, a rabbit poison, to horses, cattle, goats, chickens, dogs and cats was investigated, using extension of prothrombin time (PT) as an index of poisoning. The daily dose of pindone, administered for 5 days, ranged from 0.3 mg/kg for dogs to 2.5 mg/kg for chickens. This range of dose rates was considered to be indicative of the worst possible case that could arise following a campaign of baiting for rabbits. Although significant elevations in PT (more than double baseline values) were noted in all species other than horses, clinical signs of anticoagulant poisoning were no...
Chromogenic assay for equine plasminogen. A functional assay for equine plasminogen was established, using urokinase as the activator, a synthetic chromogenic substrate, a computer-assisted centrifugal analyzer, and acidified/neutralized plasma. One documented effect of plasma acidification appears to be inactivation of alpha-2-antiplasmin. Intra- and interassay precision testing yielded coefficients of variation of 4.1% (n = 10) and 5.6% (n = 26), respectively. Plasminogen was stable in equine plasma stored up to 1 week at 4 C and up to 5 months at -70 C. Plasminogen in nonacidified equine plasma was not activated by urokinase, strep...
The pony as an animal model for vascular implants. This study evaluated the pony as a potentially suitable model for vascular implant research. Healthy, conditioned ponies were randomly assigned to one of three groups: group I, carotid artery autografts (n = 6); group II, e-PTFE carotid interpositional grafts (n = 5); and group III, e-PTFE carotid interpositional grafts plus aspirin (10 mg/kg) and dipyridamole (3.5 mg/kg) drug administration. It was found that autografts remained patent longest (mean = 396.2 days; grafts were still patent at time of writing) followed by group III grafts (157.5 days), with group II grafts remaining patent for t...
[Pathogenesis and drug therapy of acute laminitis in horses: a literature review]. Impairment of the microcirculation in the distal part of the foot is an important factor in the aetiology of equine laminitis. To prevent the development of chronic laminitis and the resulting complications, two new therapeutical principles were tested in the treatment of acute laminitis. Thrombosis which frequently occurs in the corium of the foot, could be controlled by administration of anticoagulants such as heparin. Alpha-receptor blocking agents such as phenoxybenzamine were used, to improve the peripheral blood flow. The use of these drugs and that of anti-inflammatory agents during the...
[The progress of a fibrinolytic therapy with streptokinase, urokinase and warfarin in a thoroughbred with intermittent lameness with special reference to resonance thrombography]. 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.
Antidotal effect of vitamin K1 against warfarin-induced anticoagulation in horses. 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 ...
[The treatment of podotrochilosis with oral anticoagulants. An instruction insert desired]. 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...
Reduction of the red blood cell mass of horses: toxic effect of heparin anticoagulant therapy. This study was designed to test the efficacy of heparin anticoagulant therapy in the horse and its effect on the formed elements of blood. Nine clinically normal, nontraumatized adult horses were subjected to 4 different heparin maintenance regimens (dosages of 320, 240, 160, and 40 U/kg of body weight). Porcine intestinal mucosa heparin (20,000 U/ml) was injected subcutaneously every 12 hours for 96 hours (total 9 times). A loading dose of one-third the maintenance dose was given IV just before the first heparin injection. Three control horses were given an equivalent volume of 0.9% saline so...
Warfarin: a review with emphasis on its use in the horse. 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...
Vitamin K-dependent carboxylase in horse liver, spleen and kidney. 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...
Warfarin anticoagulation in the horse. 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.