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Topic:Coagulation
Coagulation in horses refers to the complex process by which blood forms clots, a critical function that prevents excessive bleeding following injury. This process involves a series of enzymatic reactions that lead to the transformation of liquid blood components into a stable clot. Key elements in equine coagulation include platelets, clotting factors, and fibrinogen. Abnormalities in the coagulation process can result in disorders such as excessive bleeding or thrombosis. Research in this area focuses on understanding the mechanisms of coagulation, identifying potential genetic or environmental influences, and developing diagnostic and therapeutic strategies for coagulation-related disorders in horses. This page compiles peer-reviewed research studies and scholarly articles that explore the mechanisms, regulation, and clinical implications of coagulation in equine health.
Intravascular and peritoneal coagulation and fibrinolysis in horses with acute gastrointestinal tract diseases. Components of the coagulation and fibrinolytic cascades, prothrombin and activated partial thromboplastin times, endotoxin activity, and albumin concentration were measured in blood and peritoneal fluid from 20 healthy horses and from 153 horses with acute gastrointestinal tract diseases at admission. Overall, 77% (117/153) of affected horses survived to discharge from the hospital, and 85% (82/97) of horses discharged were reported to be normal 9 to 14 months later. Significant differences in hemostatic factors were more common in peritoneal fluid than in blood. Tissue plasminogen activator, ...
Prothrombotic events in the prodromal stages of acute laminitis in horses. Prothrombotic changes occurring in the prodromal stages of carbohydrate-induced laminitis were investigated. Hemostatic alterations were evaluated by determining platelet counts, platelet survival, activated partial thromboplastin time, one-stage prothrombin time, and monocyte procoagulant activity. Thrombosis of vessels in the hoof wall was evaluated by contrast arteriography and histologic examination. Of 5 horses, 4 became lame between 28 and 52 hours after carbohydrate administration. Mean platelet count in laminitis-affected horses was lower throughout the prodromal stages of laminitis, c...
Pharmacokinetics of heparin and its pharmacodynamic effect on plasma lipoprotein lipase activity and coagulation in healthy horses. We evaluated the pharmacokinetics of IV administered sodium heparin and the pharmacodynamic effect of heparin on lipoprotein lipase (LPL) activity. Horses were allotted to 3 groups. Plasma samples were obtained from each horse before and at various times for 6 hours after heparin administration for determination of heparin concentration, LPL activity, and activated partial thromboplastin time (APTT). The disposition of heparin was dose dependent. The area under the plasma heparin concentration vs time curve (AUC) increased more than proportionally with dose, indicating that heparin elimination...
Morphologic changes of the ascending colon during experimental ischemia and reperfusion in ponies. The morphologic changes following ascending colon volvulus result from the interaction of inflammatory and coagulation mediators. The objective of this study was to establish a quantifiable histopathologic scoring system to evaluate the serial pathomorphologic changes during ischemia and reperfusion. Such a scoring system could then be applied to subsequent studies designed to attenuate bowel lesions by regulating activity of individual mediators. Ten normal, healthy adult ponies were randomly divided into two equal groups. Following anesthesia and a 30-minute stabilization period, the colon o...
Clinical pathology and hemostatic abnormalities in experimental African horsesickness. Infection of naive North American horses with 10(4) cell culture infectious doses (CCID50) of virulence variants of African horsesickness virus (AHSV), designated AHSV/4SP, AHSV/9PI, and AHSV/4PI, reproduced three classical forms of African horsesickness: acute (pulmonary), subacute (cardiac), and febrile, respectively. Distinct clinicopathologic and hemostatic abnormalities were associated with each form of disease. Hemostatic abnormalities included increased concentration of fibrin degradation products and prolongation of prothrombin, activated partial thromboplastin, and thrombin clotting t...
The hemostatic profile of equine ovarian follicular fluid. The coagulation factors VII and X and fibrinogen were detected in equine ovarian follicular fluid. The amounts of fibrinogen and factor X were approximately 40 percent of that found in normal equine plasma while the level of factor VII was lower, at approximately 14 percent. The addition of human recombinant tissue factor caused fibrin formation in the follicular fluid. The thrombin generating activity appears to be confined to the tissue factor pathway since no activity associated with factors VIII:C, IX or IX was detected. Fibrinolytic activity, at higher levels than that found in plasma, wa...
Endotoxin-induced platelet aggregation in heparinised equine whole blood in vitro. Endotoxaemia is a leading cause of death among horses. Thrombocytopenia is a common finding in clinical and experimentally-induced cases of endotoxaemia and can lead to coagulopathies, including disseminated intravascular coagulopathy which is usually fatal. In this study it was shown that endotoxin (3 ng ml-1 to 25 micrograms ml-1) can aggregate equine platelets in heparinised whole blood in vitro. The endotoxin-induced aggregation (EIA) was shown to be dependent on the presence of leucocytes in the blood and did not occur when detoxified endotoxin was used, suggesting that lipid A was necess...
Activity of coagulation and fibrinolysis parameters in animals. Using diagnostics for the determination of clotting factors and fibrinolytic parameters in human plasma, samples from rat, guinea pig, rabbit, cat, dog, sheep, cattle, horse, pig, and monkey were analysed. The human system was employed even for standard curves and controls. Results obtained in this way are relative values in relation to pooled fresh human plasma of healthy donors which is defined to contain 100% of the norm or 1 unit of each factor per 1 ml. Under these conditions, marked differences between the human clotting system and those of different animal species appear. Thus, rabbits ...
Microvascular thrombosis associated with onset of acute laminitis in ponies. The hypothesis that equine laminitis is caused by thrombosis of vessels in the laminar corium (dermis) was investigated. Hemostatic alterations were evaluated by determining platelet count, platelet survival, platelet adhesiveness to vascular subendothelium, activated clotting time, and whole blood recalcification time. Thrombosis of vessels in the hoof wall was evaluated by scintigraphic studies of the hoof wall after administration of indium-111 (111In)-labeled platelets, contrast arteriography, and histologic examination. Platelet count remained constant before and at the onset of lameness;...
Diagnosis of EDTA-dependent pseudothrombocytopenia in a horse. Thrombocytopenia in horses may be idiopathic or secondary to chronic infectious or inflammatory diseases (eg, equine infectious anemia, lymphosarcoma), drug administration, bone marrow depression, myelophthisic disease, or disseminated intravascular coagulation. This report describes EDTA-dependent pseudothrombocytopenia in a horse. Platelet counts for blood containing EDTA were consistently less than reference range, but platelet counts of blood containing heparin were within reference range. When thrombocytopenia is diagnosed in horses without clinical evidence of a bleeding tendency, EDTA-d...
Analysis of hemostasis in horses with colic. Eight tests of hemostasis were measured in 233 horses with colic. Blood samples were obtained at admission and for 4 consecutive days of hospitalization. Data were analyzed retrospectively by outcome, by broad-category diagnosis group, by small intestinal disorder, and by smaller categories for comparing specific diseases. Nonsurviving horses and horses with the most severe forms of intestinal ischemia had changes interpreted as hypercoagulative, the intensity of which was increased on the first and second mornings (sample times 2 and 3) after admission, when most significant differences for r...
Hypercoagulable state associated with a deficiency of protein C in a thoroughbred colt. Protein C is a vitamin K-dependent serine protease with anticoagulant and profibrinolytic activity which is synthesized in the liver. Decreased protein C activity was detected in a Thoroughbred colt with clinical and histopathologic evidence of recurrent venous thrombosis. Although protein C activity was reduced, protein C antigen concentration was normal. Consumptive coagulopathies produce a decrease in both the functional and antigenic concentrations of protein C, thus a defect in protein C synthesis was suspected. Inhibition of gamma-carboxylation secondary to vitamin K antagonism results i...
Administration of a receptor antagonist for platelet-activating factor during equine endotoxaemia. Platelet-activating factor (PAF) is an important mediator of endotoxaemia and various PAF receptor antagonists prevent many of the adverse effects of experimental endotoxaemia in laboratory animals. In this study a specific PAF receptor antagonist was used to investigate the role of PAF in equine endotoxaemia. At an interval of not greater than 10 days, 6 horses were each challenged with endotoxin and endotoxin with concurrent administration of SRI 63-441, a PAF receptor antagonist. The order of the treatments was randomised. Clinical signs, serum biochemical and coagulation profiles, and plat...
Additive and synergistic pharmacologic inhibition of equine fibrinoligase (factor XIIIa*-like) biochemical activity. A selected group of pharmaceutical compounds were evaluated for the ability to inhibit the biochemical activity of fibrinoligase (coagulation factor XIIIa*) in pooled equine plasma. Criteria for the pharmaceuticals selected were based on the mechanism of the transglutamination biochemical reaction mediated by coagulation factor XIIa*. These criteria were complemented by recognition of the molecular configuration and chemical composition of amino acid residue side chains involved in the process of covalent fibrin monomer polymerization (cross-linking, transglutamination) mediated by this enzyme...
Acetylsalicylic acid and blood coagulation in the horse. Equine blood may contain salicylic acid (SA) taken up as free acid or represents the metabolite of acetylsalicylic acid (ASA). To obtain information of SA in race horses we screened blood samples of trotting-horses routinely drawn to be analyzed for doping substances. The individual values determined followed a Gaussian distribution displaying a geometric mean of 19 ng SA per ml serum. A probit analysis revealed linear relationship (r = 0.995). Additional studies examined the antithrombotic efficacy of ASA in the horse. An oral dose of 300 mg ASA considerably elevated the bleeding time for mor...
Pharmacologic evaluation of factor XIIIa*-like enzyme activity in equine plasma as a potential therapeutic avenue for the inhibition of fibrinous tissue. Several pharmaceutical compounds were evaluated for their ability to selectively inhibit activated coagulation factor-XIII-like enzyme activity (eg, XIIIa*) in pooled equine plasma. Presence of coagulation factor-XIIIa*-like enzyme activity in plasma was established by assay procedures involving incorporation of the fluorescent amine compound, monodansylcadaverine, into purified casein, which served as a protein substrate. Pharmaceuticals inhibitory to coagulation factor-XIIIa*-like enzyme activity were recognized by plasma gel formation of high spectrophotometric transmittance (transparency),...
An evaluation of the effect of reagent modification on routine laboratory coagulation tests. The purpose of this study was to evaluate the effect of modifying commercial reagents for the laboratory evaluation of several haemostatic parameters in normal, non-pregnant mares. The routine coagulation screening assays, namely, the activated partial thromboplastin time (APTT) and the one-stage prothrombin time (PT), and the specific coagulation assays for the determination of the biological activity of Factors VII, VIII:C and IX, are discussed.
Disseminated intravascular coagulation associated with colic in 23 horses (1984-1989). Disseminated intravascular coagulation (DIC) secondary to colic was diagnosed in 23 horses. Each horse was categorized retrospectively as to the cause of the colic based on surgical and/or necropsy findings: group 1 consisted of 14 horses with compromised intestine that required resection and anastomosis; group 2 consisted of 3 horses with nonstrangulating intestinal displacement and/or impactions; and group 3 consisted of 6 horses with colic associated with enteritis and/or colitis. Horses were considered to be affected with DIC if at least three of five hemostatic parameters were significant...
Evaluation of the haemostatic profile in the pre- and post parturient mare, with particular focus on the perinatal period. Various haemostatic analytes were systematically evaluated for four months pre-partum and five months post partum in 14 healthy mares. The plasma fibrinogen concentration and both Factor VIII:C and von Willebrand factor activity showed gradual increases from mid-gestation and reached maximal, or near maximal activity at parturition. These increases were paralleled by an increase in plasma fibronectin concentration, the appearance of fibrinogen degradation products, and a modest rise in antithrombin III concentration. In contrast, the activity of Factor VII and Factor IX, and the one-stage prot...
Expression of procoagulant activity by equine lung macrophages: stimulation by blood lymphocytes. Increases in procoagulant activities (PCA) in equine lung macrophages were induced by non-adherent blood lymphocytes which were prestimulated with phytohaemagglutinin for 48 to 72 hours or by supernatants harvested from prestimulated blood lymphocyte cultures. However, prestimulated lymphocyte suspensions themselves expressed PCA which was most probably derived from contaminating monocytes. Because non-adherent cells from lymphocyte suspensions may have attached to adherent macrophages, cells within lymphocyte suspensions might have contributed to the PCAs expressed by lymphocyte-stimulated lu...
Whole blood re-calcification time in equine colic. Whole blood re-calcification times were evaluated as a measure of endotoxin-associated coagulopathy in horses. First, the effects of endotoxin concentration and duration of in vitro incubation of citrated whole blood with endotoxin on the whole blood re-calcification time of blood collected from healthy horses were determined. Increasing concentrations or incubation times of endotoxin accelerated the whole blood re-calcification time. This effect was attributed mainly to increased monocyte thromboplastin activity. Second, whole blood re-calcification time, a clotting profile, plasma factor VII...
Effects of exploratory laparotomy on plasma and peritoneal coagulation/fibrinolysis in horses. Plasma and peritoneal fluid samples were collected before and after surgery from 6 horses undergoing a ventral midline exploratory laparotomy and from 6 anesthetized control horses. Coagulation/fibrinolytic components measured in the plasma and peritoneal fluid of these horses included the functional activity of antithrombin III, alpha-2 antiplasmin, plasminogen, and protein C, and the concentrations of fibrinogen and fibrin degradation products. Peritoneal fluid antithrombin III, fibrin degradation products, and plasminogen values were significantly increased after surgery (over time) in prin...
Endotoxemia in horses. A review of cellular and humoral mediators involved in its pathogenesis. Endotoxemia remains the leading cause of death in horses, being intimately involved in the pathogenesis of gastrointestinal disorders that cause colic and neonatal foal septicemia. Endotoxins, normally present within the bowel, gain access to the blood across damaged intestinal mucosa, or endotoxemia occurs when gram negative organisms proliferate in tissues. Endotoxins are removed from the circulation by the mononuclear phagocyte system, and the response of mononuclear phagocytes to these lipopolysaccharides (LPS) play an important role in determining the severity of clinical disease. Macroph...
Hemostatic studies in racing standardbred horses with exercise-induced pulmonary hemorrhage. Hemostatic parameters at rest and after moderate exercise. The purpose of this study was to determine whether a defect in hemostasis might be a factor in the etiology of exercise-induced pulmonary hemorrhage (EIPH). Hemostatic parameters were evaluated in 22 EIPH-positive and ten EIPH-negative racing horses while in a rested state. Nineteen EIPH-positive and ten EIPH-negative horses were further evaluated just before and immediately after a 15 min exercise period on a 260 m oval track. When EIPH-positive and EIPH-negative horses were compared at rest, there was no significant difference in any of the coagulation and fibrinolytic parameters studied. Th...
Clinical relevance of monocyte procoagulant activity in horses with colic. Endotoxin-activated monocytes express a thromboplastin-like procoagulant activity on the cell surface that may serve as a focal point for formation of microvascular thrombi. Because coagulopathy is a common sequela to endotoxemia in the equine species, we investigated the ability of monocytes, isolated from horses with colic, to express procoagulant activity. On the day of admission, and on the third and fifth day of hospitalization, monocytes were isolated from 30 adult horses with colic. A coagulation profile, including prothrombin time, activated partial thromboplastin time, thrombin time, ...
Bleeding disorder (von Willebrand disease) in a quarter horse. Bleeding diathesis in a Quarter Horse filly was caused by von Willebrand disease. Hemorrhage occurred mainly from mucosal surfaces and after trauma. Quantitative and qualitative measurements of plasma von Willebrand factor (vWF) documented a specific deficiency of vWF high molecular weight multimers, and concurrently greater than expected deficiency of vWF activity relative to vWF concentration. These findings are characteristic of type-II von Willebrand disease in human beings. Application of vWF assays used in human and small animal medicine now permits evaluation of vWF and diagnosis of von...
Low dose calcium heparin in horses: plasma heparin concentrations, effects on red blood cell mass and on coagulation variables. Low dose calcium heparin was administered subcutaneously at 12 hourly intervals to six healthy horses at an initial dose of 150 iu of heparin/kg bodyweight (bwt) and at a maintenance dose of 120 iu/kg bwt. All injections were given at 0900 and 2100 h. Blood samples for monitoring plasma heparin concentrations were obtained prior to, at 2 hourly intervals for 84 h (treatment period), and at Hours 24, 32, 48 and 96 of the control period. Blood samples for monitoring red blood cell (RBC) mass, plasma antithrombin III activity (AT III), activated partial thromboplastin time (APTT), and thrombin ti...
Clinical signs, laboratory changes and toxicokinetics of brodifacoum in the horse. Six horses gavaged with a commercial brodifacoum (BDF)-containing bait (Talone) at a dosage of 0.125 mg of BDF/kg of body weight showed weight loss, severe hypocoagulability and hemogram alterations. Four of the horses became depressed and anorectic; one required vitamin K1 therapy. Increases in clotting times were observed at 24 h in the partial thromboplastin time (PTT) followed by the thrombotest (TBT) and one-stage prothrombin time (PT) at 48 h. Elevated mean PTT, PT and TBT were observed from days 4 to 8 (p less than 0.05) with levels returning to pretreatment levels by day 12. Maximum pr...
