Fibrinolysis is a physiological process in horses that involves the breakdown of fibrin, a fibrous protein involved in blood clotting. This process is essential for the removal of clots and the maintenance of normal blood flow following tissue repair or injury. Fibrinolysis is mediated by a series of enzymes, with plasmin being the primary enzyme responsible for degrading fibrin. The balance between fibrin formation and fibrinolysis is critical for hemostasis and preventing thrombosis. In horses, dysregulation of fibrinolysis can be associated with various health conditions, such as laminitis and equine metabolic syndrome. This page compiles peer-reviewed research studies and scholarly articles that explore the mechanisms, regulation, and clinical implications of fibrinolysis in equine health.
Pliszczak-Król A, Gemra M, Kozdrowski R, Zalewski D, Iwaszko A.Recurrent Airway Obstruction (RAO), also called severe asthma or heaves, is a chronic disease in adult horses caused by aeroallergens from straw or hay. Disturbances in hemostasis (intensified coagulation and depressed fibrinolysis) are considered one of the prominent reasons of inflammatory process, injury and dysfunction of the lungs. The aim of the study was to evaluate chosen parameters of hemostasis in horses with active form of RAO. Ten RAO-horses (group R) and ten healthy horses (group C) were exposed to straw and hay allergen challenge. The prothrombin time (PT), activated partial thro...
Ness SL, Frye AH, Divers TJ, Rishniw M, Erb HN, Brooks MB.OBJECTIVE To determine effects of oral administration of Yunnan Baiyao on platelet activation, coagulation, and fibrinolysis in healthy horses. ANIMALS 12 healthy adult horses. PROCEDURES In a randomized blinded crossover study that included a 4-week washout period between treatments, horses were orally administered a paste containing Yunnan Baiyao (15 mg/kg) or placebo at 12-hour intervals for 3 days. Blood samples were collected before start of treatment (time 0) and at 24 and 72 hours for a CBC, measurement of fibrinogen concentration, coagulation screening tests, and a panel of assays to a...
Navas de Solís C, Reef VB, Slack J, Jose-Cunilleras E.To evaluate horses with atrial fibrillation for hypercoagulability; plasma D-dimer concentrations, as a marker of a procoagulant state; and a relationship between coagulation profile results and duration of atrial fibrillation or presence of structural heart disease. Methods: Case-control study. Methods: Plasma samples from 42 horses (25 with atrial fibrillation and 17 without cardiovascular or systemic disease [control group]). Methods: Results of hematologic tests (ie, plasma fibrinogen and D-dimer concentrations, prothrombin and activated partial thromboplastin times, and antithrombin activ...
Epstein KL.Although primary coagulopathies are rare in horses, changes in coagulation and fibrinolysis are commonly associated with inflammatory diseases. A clear understanding of the pathophysiology of normal and abnormal hemostasis is required to be able to choose and interpret diagnostic tests evaluating coagulation and fibrinolysis. After diagnosis, treatment of the underlying disease must occur regardless of whether clinical manifestations (excessive bleeding or thrombosis) of the coagulopathy are present or not. Specific treatment may be initiated if there are clinical signs of coagulopathy.
Fletcher DJ, Brainard BM, Epstein K, Radcliffe R, Divers T.Antifibrinolytic drugs such as epsilon aminocaproic acid (EACA) and tranexamic acid (TEA) are used to treat various bleeding disorders in horses. Although horses are hypofibrinolytic compared to humans, dosing schemes have been derived from pharmacokinetic studies targeting plasma concentrations in humans. Objective: We hypothesized therapeutic plasma concentrations of antifibrinolytic drugs in horses would be significantly lower than in humans. Our objective was to use thromboleastography (TEG) and an in vitro model of hyperfibrinolysis to predict therapeutic concentrations of EACA and TEA in...
Olver CS, Nielsen VG.Carboxyheme and metheme states modulate hemostasis in humans and other species. Further, carbon monoxide and/or nitric oxide production increase in inflammatory disorders involving the gastrointestinal tract, with associated hypercoagulability or hypocoagulability. In particular, the horse suffers both thrombotic or coagulopathic complications during acute gastrointestinal disease. This investigation characterized the thrombelastographic response to carboxyheme (via CORM-2) or metheme (via phenylhydroxylamine, PHA) states without/with addition of tissue type plasminogen activator. Citrated pla...
Ribera T, Monreal L, Delgado MA, Ríos J, Prades M.To assess the synovial fibrinolytic pathway activation in adult horses with developmental and degenerative arthropathies such as osteochondritis dissecans (OCD) and osteoarthritis (OA) by measuring synovial D-dimer concentrations. Methods: Prospective observational clinical study of horses admitted for OCD or OA. Synovial fluid was collected during lameness examination or prior to the surgical procedure, and D-dimer concentration and routine synovial fluid analysis were performed. Results: Fifty-eight horses (14 with OCD, 10 with OA and 34 controls) were included in this study. Synovial D-dime...
Dunkel B, Chan DL, Boston R, Monreal L.Coagulopathies are common in horses with ischemic or inflammatory gastrointestinal (GI) disturbances. There is indirect evidence suggesting that early stages of these diseases are characterized by hypercoagulability (HC). Objective: HC, assessed via thromboelastography (TEG), is common in horses with ischemic or inflammatory GI diseases. The degree of HC is correlated with nonsurvival and thrombotic complications. Methods: Thirty client-owned horses with ischemic or inflammatory GI disease, 30 client-owned horses with nonischemic or inflammatory GI disease, and 30 healthy horses (control group...
Ross J, Dallap BL, Dolente BA, Sweeney RW.To determine the pharmacokinetics and pharmacodynamics of epsilon-aminocaproic acid (EACA), including the effects of EACA on coagulation and fibrinolysis in healthy horses. Methods: 6 adult horses. Methods: Each horse received 3.5 mg of EACA/kg/min for 20 minutes, i.v. Plasma EACA concentration was measured before (time 0), during, and after infusion. Coagulation variables and plasma alpha(2)-antiplasmin activity were evaluated at time 0 and 4 hours after infusion; viscoelastic properties of clot formation were assessed at time 0 and 0.5, 1, and 4 hours after infusion. Plasma concentration ver...
Stokol T, Erb HN, De Wilde L, Tornquist SJ, Brooks M.Fibrin(ogen) degradation products (FDPs) and D-dimer are sensitive indicators of excessive fibrinolysis due to disseminated intravascular coagulation (DIC) in dogs. To the authors' knowledge, latex-agglutination-based plasma FDP and D-dimer assays have not been validated for use in horses. Objective: To determine: 1) sensitivity and specificity of latex agglutination serum and plasma FDP and D-dimer assays for diagnosis of DIC; and 2) their prognostic value in horses with severe colic. Methods: At hospital admission and 24 hours later, blood was collected from 30 healthy horses and 20 horses w...
Monreal L, Anglés A, Espada Y, Monasterio J, Monreal M.Changes in haemostasis in horses with colic were assessed by using specific and sensitive markers of coagulation and fibrinolysis activity. Blood samples from 41 horses with severe colic and from 30 healthy control horses were tested. Diagnosis of DIC was based on the findings of at least 3 of 6 abnormalities: thrombocytopenia, prolonged clotting times (PT and APTT), increased polyclonal FDPs, decreased fibrinogen and decreased AT-III activity. Plasma thrombin-antithrombin III complexes (TAT), monoclonal fibrin degradation products fragment D (D-dimer) and monoclonal fibrinogen degradation pro...
Kawcak CE, Baxter GM, Getzy DM, Stashak TS, Chapman PL.To measure arterial and venous blood gas, coagulation, and fibrinolysis variables in blood from isolated segments of control and ischemic large colons for the purpose of identifying variables for rapid, indirect assessment of colonic mucosal injury. Methods: Variables were determined at specific intervals during the 4-hour study (3 hours of ischemia and 1 hour of reperfusion). Methods: Seven clinically normal horses between 2 and 15 years old. Methods: Horses underwent laparotomy and occlusion of the lumen and vasculature of the mid-portion of the pelvic flexure of the large colon. During isch...
Collatos C, Barton MH, Schleef R, Prasse KW, Moore JN.Much of the pathophysiology associated with equine gastrointestinal diseases is attributed to the effects of endotoxin on haemostasis. Because little is known about the responses of the equine fibrinolytic system to endotoxin, regulation of the system was investigated. Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1) were identified as the primary plasminogen activator and plasminogen activator inhibitor, respectively, in equine blood. Under experimental conditions, the equine fibrinolytic system responded to endotoxin in a manner similar to that repo...
Prasse KW, Allen D, Moore JN, Duncan A.The balance of coagulation and fibrinolysis was studied in 15 horses during the prodromal stages of acute laminitis induced by carbohydrate overload. Progression of the disease was stopped 12 to 24 hours before the expected onset of lameness in trial 1 (8 horses) and at the onset of lameness in trial 2 (7 horses). The end points in each trial were identified by specific changes in blood pressures (trial 1) and by changes in pulse, rectal temperature, and arterial pressure (trial 2) that were anticipated on the basis of original description of the experimental model. Blood samples for hemostasi...
McKeever KH, Hinchcliff KW, Kociba GJ, Reed SM, Muir WW.Changes in clotting time (CT) and fibrinolytic activity (FA) were evaluated in 6 mature, female horses during exercise. Two trials were performed on consecutive days, using a randomized crossover design. Each mare was assigned to either an exercise trial or a control trial on the first day, and to the alternate trial 24 hours later. Mares exercised for 20 minutes on a treadmill at an elevation of 2 degrees and a velocity of 5 m/s. Venous blood samples were collected immediately before exercise, at 4, 8, 12, 16 and 20 minutes during exercise, and 15 minutes after cessation of exercise. Blood wa...
Epstein KL.Although primary coagulopathies are rare in horses, changes in coagulation and fibrinolysis are commonly associated with inflammatory diseases. A clear understanding of the pathophysiology of normal and abnormal hemostasis is required to be able to choose and interpret diagnostic tests evaluating coagulation and fibrinolysis. After diagnosis, treatment of the underlying disease must occur regardless of whether clinical manifestations (excessive bleeding or thrombosis) of the coagulopathy are present or not. Specific treatment may be initiated if there are clinical signs of coagulopathy.
Navas de Solís C, Reef VB, Slack J, Jose-Cunilleras E.To evaluate horses with atrial fibrillation for hypercoagulability; plasma D-dimer concentrations, as a marker of a procoagulant state; and a relationship between coagulation profile results and duration of atrial fibrillation or presence of structural heart disease. Methods: Case-control study. Methods: Plasma samples from 42 horses (25 with atrial fibrillation and 17 without cardiovascular or systemic disease [control group]). Methods: Results of hematologic tests (ie, plasma fibrinogen and D-dimer concentrations, prothrombin and activated partial thromboplastin times, and antithrombin activ...
Stokol T, Erb HN, De Wilde L, Tornquist SJ, Brooks M.Fibrin(ogen) degradation products (FDPs) and D-dimer are sensitive indicators of excessive fibrinolysis due to disseminated intravascular coagulation (DIC) in dogs. To the authors' knowledge, latex-agglutination-based plasma FDP and D-dimer assays have not been validated for use in horses. Objective: To determine: 1) sensitivity and specificity of latex agglutination serum and plasma FDP and D-dimer assays for diagnosis of DIC; and 2) their prognostic value in horses with severe colic. Methods: At hospital admission and 24 hours later, blood was collected from 30 healthy horses and 20 horses w...
Ness SL, Frye AH, Divers TJ, Rishniw M, Erb HN, Brooks MB.OBJECTIVE To determine effects of oral administration of Yunnan Baiyao on platelet activation, coagulation, and fibrinolysis in healthy horses. ANIMALS 12 healthy adult horses. PROCEDURES In a randomized blinded crossover study that included a 4-week washout period between treatments, horses were orally administered a paste containing Yunnan Baiyao (15 mg/kg) or placebo at 12-hour intervals for 3 days. Blood samples were collected before start of treatment (time 0) and at 24 and 72 hours for a CBC, measurement of fibrinogen concentration, coagulation screening tests, and a panel of assays to a...
McKeever KH, Hinchcliff KW, Kociba GJ, Reed SM, Muir WW.Changes in clotting time (CT) and fibrinolytic activity (FA) were evaluated in 6 mature, female horses during exercise. Two trials were performed on consecutive days, using a randomized crossover design. Each mare was assigned to either an exercise trial or a control trial on the first day, and to the alternate trial 24 hours later. Mares exercised for 20 minutes on a treadmill at an elevation of 2 degrees and a velocity of 5 m/s. Venous blood samples were collected immediately before exercise, at 4, 8, 12, 16 and 20 minutes during exercise, and 15 minutes after cessation of exercise. Blood wa...
Ribera T, Monreal L, Delgado MA, Ríos J, Prades M.To assess the synovial fibrinolytic pathway activation in adult horses with developmental and degenerative arthropathies such as osteochondritis dissecans (OCD) and osteoarthritis (OA) by measuring synovial D-dimer concentrations. Methods: Prospective observational clinical study of horses admitted for OCD or OA. Synovial fluid was collected during lameness examination or prior to the surgical procedure, and D-dimer concentration and routine synovial fluid analysis were performed. Results: Fifty-eight horses (14 with OCD, 10 with OA and 34 controls) were included in this study. Synovial D-dime...
Dunkel B, Chan DL, Boston R, Monreal L.Coagulopathies are common in horses with ischemic or inflammatory gastrointestinal (GI) disturbances. There is indirect evidence suggesting that early stages of these diseases are characterized by hypercoagulability (HC). Objective: HC, assessed via thromboelastography (TEG), is common in horses with ischemic or inflammatory GI diseases. The degree of HC is correlated with nonsurvival and thrombotic complications. Methods: Thirty client-owned horses with ischemic or inflammatory GI disease, 30 client-owned horses with nonischemic or inflammatory GI disease, and 30 healthy horses (control group...
Fletcher DJ, Brainard BM, Epstein K, Radcliffe R, Divers T.Antifibrinolytic drugs such as epsilon aminocaproic acid (EACA) and tranexamic acid (TEA) are used to treat various bleeding disorders in horses. Although horses are hypofibrinolytic compared to humans, dosing schemes have been derived from pharmacokinetic studies targeting plasma concentrations in humans. Objective: We hypothesized therapeutic plasma concentrations of antifibrinolytic drugs in horses would be significantly lower than in humans. Our objective was to use thromboleastography (TEG) and an in vitro model of hyperfibrinolysis to predict therapeutic concentrations of EACA and TEA in...
Prasse KW, Allen D, Moore JN, Duncan A.The balance of coagulation and fibrinolysis was studied in 15 horses during the prodromal stages of acute laminitis induced by carbohydrate overload. Progression of the disease was stopped 12 to 24 hours before the expected onset of lameness in trial 1 (8 horses) and at the onset of lameness in trial 2 (7 horses). The end points in each trial were identified by specific changes in blood pressures (trial 1) and by changes in pulse, rectal temperature, and arterial pressure (trial 2) that were anticipated on the basis of original description of the experimental model. Blood samples for hemostasi...
Collatos C, Barton MH, Schleef R, Prasse KW, Moore JN.Much of the pathophysiology associated with equine gastrointestinal diseases is attributed to the effects of endotoxin on haemostasis. Because little is known about the responses of the equine fibrinolytic system to endotoxin, regulation of the system was investigated. Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1) were identified as the primary plasminogen activator and plasminogen activator inhibitor, respectively, in equine blood. Under experimental conditions, the equine fibrinolytic system responded to endotoxin in a manner similar to that repo...
Pliszczak-Król A, Gemra M, Kozdrowski R, Zalewski D, Iwaszko A.Recurrent Airway Obstruction (RAO), also called severe asthma or heaves, is a chronic disease in adult horses caused by aeroallergens from straw or hay. Disturbances in hemostasis (intensified coagulation and depressed fibrinolysis) are considered one of the prominent reasons of inflammatory process, injury and dysfunction of the lungs. The aim of the study was to evaluate chosen parameters of hemostasis in horses with active form of RAO. Ten RAO-horses (group R) and ten healthy horses (group C) were exposed to straw and hay allergen challenge. The prothrombin time (PT), activated partial thro...
Kawcak CE, Baxter GM, Getzy DM, Stashak TS, Chapman PL.To measure arterial and venous blood gas, coagulation, and fibrinolysis variables in blood from isolated segments of control and ischemic large colons for the purpose of identifying variables for rapid, indirect assessment of colonic mucosal injury. Methods: Variables were determined at specific intervals during the 4-hour study (3 hours of ischemia and 1 hour of reperfusion). Methods: Seven clinically normal horses between 2 and 15 years old. Methods: Horses underwent laparotomy and occlusion of the lumen and vasculature of the mid-portion of the pelvic flexure of the large colon. During isch...
Ross J, Dallap BL, Dolente BA, Sweeney RW.To determine the pharmacokinetics and pharmacodynamics of epsilon-aminocaproic acid (EACA), including the effects of EACA on coagulation and fibrinolysis in healthy horses. Methods: 6 adult horses. Methods: Each horse received 3.5 mg of EACA/kg/min for 20 minutes, i.v. Plasma EACA concentration was measured before (time 0), during, and after infusion. Coagulation variables and plasma alpha(2)-antiplasmin activity were evaluated at time 0 and 4 hours after infusion; viscoelastic properties of clot formation were assessed at time 0 and 0.5, 1, and 4 hours after infusion. Plasma concentration ver...
Olver CS, Nielsen VG.Carboxyheme and metheme states modulate hemostasis in humans and other species. Further, carbon monoxide and/or nitric oxide production increase in inflammatory disorders involving the gastrointestinal tract, with associated hypercoagulability or hypocoagulability. In particular, the horse suffers both thrombotic or coagulopathic complications during acute gastrointestinal disease. This investigation characterized the thrombelastographic response to carboxyheme (via CORM-2) or metheme (via phenylhydroxylamine, PHA) states without/with addition of tissue type plasminogen activator. Citrated pla...
Monreal L, Anglés A, Espada Y, Monasterio J, Monreal M.Changes in haemostasis in horses with colic were assessed by using specific and sensitive markers of coagulation and fibrinolysis activity. Blood samples from 41 horses with severe colic and from 30 healthy control horses were tested. Diagnosis of DIC was based on the findings of at least 3 of 6 abnormalities: thrombocytopenia, prolonged clotting times (PT and APTT), increased polyclonal FDPs, decreased fibrinogen and decreased AT-III activity. Plasma thrombin-antithrombin III complexes (TAT), monoclonal fibrin degradation products fragment D (D-dimer) and monoclonal fibrinogen degradation pro...
