Endotoxin-induced changes in the hemostatic system in neonatal calves: the effect of antiserum to a mutant Escherichia coli (J-5)

Changes in the hemostatic system were studied in 22 neonatal calves given a small dosage of Escherichia coli endotoxin (0.5 microgram/kg) by slow (5-hour) IV infusion. The effect of pretreatment with an antiserum to mutant of E coli O111:B4 (J-5) was evaluated. The platelet count, plasma fibrinogen concentration, prothrombin time, and activated partial thromboplastin time changed significantly from base line during and after endotoxin infusions in all calves. The mean platelet count was significantly decreased from 1 through 24 hours after endotoxin infusion was started. Mean plasma fibrinogen was decreased 2 through 12 hours after endotoxin infusion was started. The mean prothrombin time and activated partial thromboplastin time were significantly greater than base line at 3 to 6 hours and 3 to 12 hours, respectively, after endotoxin infusion was started. Serum concentration of fibrinolytic degradation products remained less than 10 micrograms/ml. Bovine J-5 antiserum did not prevent the endotoxin-induced changes in the hemostatic system of these neonatal calves.     

Hemostatic response to surgical neutering via ovariectomy and ovariohysterectomy in dogs

Objective-To investigate the hemostatic response to surgery and compare the response for ovariohysterectomy with that for ovariectomy and to evaluate the usefulness of thromboelastography on plasma samples. Animals-42 female dogs. Procedures-Dogs were assigned to undergo ovariohysterectomy or ovariectomy. Blood samples were collected immediately before and 1, 6, and 24 hours after surgery and stored at -80°C for subsequent analysis. Plasma samples were subjected to thromboelastography after thawing. In addition, coagulation variables were measured, including concentrations of von Willebrand factor antigen, fibrinogen, antithrombin, and protein C; activity of factor VIII; activated partial thromboplastin time; prothrombin time; and thrombin time. The fibrinolytic response was assessed via concentrations of D-dimer, plasminogen, and α-2-antiplasmin (plasmin inhibitor). Results-Substantial hemostatic and fibrinolytic activation was evident after surgery in both groups, as characterized by significantly increased global clot strength and an overall hypercoagulable state at 4 hours after surgery in addition to decreases in von Willebrand factor antigen and factor VIII concentrations and shortened prothrombin and thrombin times. The dogs also typically had activation of the fibrinolytic system, as evidenced by increased postoperative concentrations of D-dimer, plasminogen, and plasmin inhibitor. Differences between the 2 groups could not be detected for any variables. Conclusions and Clinical Relevance-Elective surgery with limited tissue trauma induced hemostatic activation in dogs, which led to hypercoagulability after surgery. A difference between the ovariohysterectomy and ovariectomy groups was not detected. Thromboelastography can be used on plasma samples and may be useful for evaluating patterns over time.     

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 activity and plasma endotoxin concentration on blood samples obtained from 35 equine colic patients and 10 healthy horses were determined. Compared with healthy horses, colic patients had a longer mean whole blood re-calcification and prothrombin time, lower per cent factor VII activity and higher mean fibrin degradation products concentration. Within the colic patient group, horses that did not survive had detectable endotoxin in plasma, longer whole blood re-calcification and prothrombin times, and lower plasma factor VII activity, compared with colic patients that survived. These data indicate that colic patients with endotoxaemia experience hypercoagulable states, followed by consumptive coagulopathy. Although the cause of endotoxin-associated coagulopathy is likely multi-factorial, increased expression of monocyte thromboplastin activity may be involved in the pathogenesis of coagulopathy. The whole blood recalcification time is a simple, fast and inexpensive way to detect coagulopathy during endotoxaemia and determine the prognosis for survival.     

Plasma D-dimer concentration in sick newborn foals

BACKGROUND: Septicemia is associated with a systemic inflammatory response, hemostatic activation, and disseminated intravascular coagulopathy (DIC). HYPOTHESIS: Increased plasma d-dimer concentration occurs in septic neonates and can reliably detect sepsis or DIC, and predict death in ill neonatal foals. ANIMALS: 40 septic, 41 nonseptic hospitalized foals, and 22 healthy neonates. METHODS: Prospective observational clinical study. Blood samples were collected on admission, at 24-48 hours after admission, and at the time of discharge or euthanasia. Plasma d-dimer concentration, clotting times, antithrombin activity, and fibrinogen concentration were determined. RESULTS: On admission, d-dimer concentration values were significantly higher in septic foals (median, 25-75th percentiles; 568, 245-2013 ng/mL) compared with the nonseptic and healthy groups (386, 175-559 and 313, 152-495 ng/mL, respectively), and in septic foals at the age of 2-7 days compared with similar-age nonseptic foals. By means of samples taken at 24-48 hours of hospitalization and a cut-off value of > 2000 ng/mL, D dimer concentration was significantly associated with the diagnosis of septicemia (odds ratio [OR] = 19.6, 95% confidence interval [95% CI] 1.9-203) and death (OR = 8.7, 95% CI 1.8-43). Owing to a high false-positive prediction rate (71%), a normal d-dimer concentration is better at eliminating the diagnosis of sepsis than an increased d-dimer concentration at predicting sepsis. Fifty percent of septic foals had a diagnosis of DIC, but d-dimer concentration was not significantly associated with the diagnosis of DIC. CONCLUSIONS AND CLINICAL IMPORTANCE: Septic foals showed a marked activation of coagulation and fibrinolytic systems and a high prevalence of DIC. Increased plasma d-dimer concentration is significantly associated with the diagnosis of sepsis.     

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 significantly abnormal: decreased antithrombin III (AT III) values, increased level of fibrin degradation products (FDP), thrombocytopenia, prolonged activated partial thromboplastin time, and prolonged prothrombin time. The most consistent hemostatic abnormalities were decreased AT III activity, increased FDP titers, and thrombocytopenia. Clotting times were more variable and did not always correlate with the presence of excessive hemorrhage. Excessive hemorrhage was present during surgery in seven horses and occurred within 1 to 12 hours after surgery in nine other horses. In addition to treatment of the primary disease, 19 horses received treatment for DIC consisting of heparin and/or plasma or fresh whole blood transfusions. Heparin alone was used in 12 horses. Heparin, in addition to fresh whole blood transfusions or fresh plasma, was administered to four horses. Three horses were treated with plasma alone. Four other horses were not treated specifically for the DIC. Eight horses (34%) survived the acute coagulopathy. Although a greater proportion of the surviving horses received heparin therapy (87.5%; 7/8) than did those that died (60%; 9/15), the difference was not statistically significant (P = 0.345).(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of viscoelastic coagulation analysis and standard coagulation profiles in critically ill neonatal foals to outcome

Objective – To determine if changes in viscoelastic variables are associated with abnormalities observed in the standard coagulation profile and patient outcome in foals with suspected septicemia. Design – Prospective clinical trial during 2003 and 2004 foal season. Setting – Neonatal intensive care unit at a veterinary teaching hospital. Animals – Thirty critically ill foals <72‐hour‐old admitted sequentially meeting criteria for systemic inflammatory response associated with infection. Interventions – Hemostatic evaluation, using standard coagulation testing and viscoelastic analysis, was performed at admission, 24 hours following admission, and 48 hours following admission in critically ill foals. Standard coagulation tests included platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen, fibrin(ogen) degradation products, and antithrombin. Data collected from viscoelastic analysis included time to initial clot formation (ACT), clot rate, and platelet function. Signalment, blood culture results, clinicopathologic data, and outcome were collected from medical records. Equality of populations test was used to determine associations between coagulation tests and blood culture status/outcome, as well as between viscoelastic parameters and coagulopathy, blood culture status, and outcome. Logistic regression was used to quantify associations. A significance level of P<0.05 was used. Measurements and Main Results – Foals with decreasing clot rate (CR) over the sample period were more likely to be euthanized or die (P=0.02). Foals with prolonged ACT (P=0.03), and decreased CR at admission (P=0.047), were more commonly coagulopathic. Identification of coagulopathy on admission (P=0.02), or persistence of hemostatic dysfunction 48 hours later (P=0.04), was associated with death. Conclusions – Viscoelastic coagulation evaluation could be used in a neonatal intensive care unit setting to further characterize coagulopathy, and identify foals at higher risk for poor outcome.     

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, and plasma fibrinogen and serum fibrin degradation products concentrations, was determined at each sample collection. The concentration of endotoxin in the plasma was quantitated at the time of admission. Ten clinically normal adult horses served as controls. The procoagulant activity of monocytes isolated from horses with colic was significantly (P less than 0.05) greater than that of the monocytes isolated from clinically normal horses. On the first and third day of hospitalization, the mean prothrombin time was significantly (P less than 0.05) longer in horses with colic, compared with clinically normal horses, and was the most common abnormality in the coagulation profile on the day of admission (25/30; 83%). Mean fibrin degradation products concentration was significantly (P less than 0.05) greater in horses with colic on the day of admission and was the second most common abnormality in the coagulation profile on day 1 (23/30; 77%). In horses with colic, the mean prothrombin and activated partial thromboplastin times were significantly (P less than 0.05) longer in horses that did not survive, compared with horses that survived.(ABSTRACT TRUNCATED AT 250 WORDS)     

Preoperative and postoperative hemostatic profiles of dogs undergoing ovariohysterectomy.

Hemostatic profiles were evaluated in 15 healthy dogs immediately before and 24 hours after celiotomy for routine ovariohysterectomy. Prothrombin time, activated partial thromboplastin time, fibrinogen, fibrin degradation products, antithrombin III activity, platelet count, and hemogram were measured. There were no significant changes in prothrombin time, activated partial thromboplastin time, fibrin degradation products, antithrombin III activity, or platelet count. Fibrinogen concentration was significantly higher following surgery. Postoperative leukocyte differential counts were typical of stress leukograms, and were characterized by leukocytosis, neutrophilia, lymphopenia and eosinopenia. Mild decreases in packed cell volume, red blood cell count and hemoglobin concentration were consistent with minor blood loss during surgery or fluid retention and hemodilution postoperatively. It was concluded that celiotomy and routine ovariohysterectomy in healthy dogs did not alter hemostatic profiles 24 hours after surgery. Abnormal postoperative hemostatic profiles should not be attributed to surgery alone; other causes of abnormal hemostatic profiles should be investigated.     

Haemodynamic, pathological, haematological and behavioural changes during endotoxin infusion in equine neonates

The purpose of this study was to evaluate the effects of experimentally induced sublethal endotoxaemia in equine neonates. Four foals, between two and five days of age, were infused intravenously with 0.5 microgram/kg bodyweight of Salmonella typhimurium endotoxin (LPS) over a 5 h period. A four-day-old and a five-day-old foal, similarly infused with sterile isotonic saline, served as controls. Clinical signs were monitored, blood samples obtained for evaluation of selected haematological and biochemical parameters; and haemodynamic parameters were recorded hourly during the infusion, as well as 6 and 24 h post infusion. Depression, anorexia, increased rectal temperature, leucopenia followed by leucocytosis, hypoglycaemia, increased prothrombin time, partial thromboplastin time (APTT), pulmonary artery pressure, pulmonary artery wedge pressure, right atrial pressure, pulmonary and systemic vascular resistance and mild hypoxaemia were consistent findings in the foals receiving endotoxin. There was marked variation over time in the above parameters, during the infusion. Shock was not induced, and the foals appeared to be healthy shortly after the infusion was discontinued. The return to baseline values of body temperature (3 of 4 foals), APTT (1 of 4 foals) and neutrophil count (2 of 4 foals), during endotoxin infusion, suggests induction of early tolerance. The control foals remained alert and the temperature, prothrombin time and fibrinogen remained stable during the study. Hyperglycaemia, transient increased APTT and variations in selected haemodynamic parameters were recorded in the control foals during the infusion.     

Plasma Endotoxin Concentrations in Clinically Normal and Potentially Septic Equine Neonates

Plasma endotoxin concentrations were measured at 1 to 2 and 5 to 6 days of age in clinically normal foals and in potentially septic neonatal foals admitted to North Carolina State University's Veterinary Teaching Hospital for a variety of conditions. In 1 to 2 and 5 to 6 day old normal foals, median plasma endotoxin concentrations were 2.17 (range, 1.61–2.54; n = 6) and 2.89 (range, 2.61–3.50; n = 7) endotoxin units/mL (EU/mL), respectively. Median plasma endotoxin concentration in potentially septic foals with negative blood cultures or gram positive isolates (n = 8) was 2.73 (range, 0.59–4.04) EU/mL. In hospitalized foals with gram negative isolates (n = 6), median plasma endotoxin concentration was 78.06 (range, 0.76–2,696.41) EU/mL, but individual endotoxin values were only increased in foals that were extremely sick and died within hours of sampling. Plasma endotoxin concentrations were significantly greater in foals with sepsis scores ≥ 11 compared with foals with sepsis scores ≤ 10. Increased plasma endotoxin concentrations appear to predict an unfavorable outcome in septic foals, but normal endotoxin concentrations do not appear to have any predictive value. (Journal of Veterinary Internal Medicine 1993; 7:296–302. Copyright © 1993 by the American College of Veterinary Internal Medicine.)     

Changes in Hemostatic Indices in Foals Naturally Infected With Strongylus vulgaris

Strongylus vulgaris has been found endemic in equine populations subject to parasite control by targeted selective anthelmintic therapy. This study investigated hemostasis in foals naturally infected with S. vulgaris and monitored this response over the course of progressing infection stages. The hemostatic indices D-dimer, antithrombin III (ATIII), fibrinogen, prothrombin time (PT), and activated partial thromboplastin time were evaluated in weekly blood samples for up to 50 weeks in 12 foals born into a herd with high prevalence of S. vulgaris. Results were compared with weekly S. vulgaris antibody enzyme-linked immunosorbent assay values in all foals using a linear mixed effects model with repeated measures and to total numbers of S. vulgaris larvae in nine foals at necropsy with Pearson linear correlation. In the first week of life, all evaluated indices of hemostasis were significantly different from those observed in the rest of the study weeks, corresponding to previously demonstrated aberrancies in neonates. Significant changes were seen for D-dimer in weeks 11–24, 26–27, 30, and 39 compared with week 2, for PT in weeks 12–13 compared with week 6, and for ATIII in week 15 compared with week 4. Strongylus vulgaris antibody levels were statistically associated with D-dimer (P = .0076) and fibrinogen (P = .0004) concentrations. Naturally acquired infection with S. vulgaris was associated with changes suggestive of mild activation of coagulation, fibrinolysis, and inflammation. The results of this study may help elucidate the pathogenesis of the endarteritis, thromboembolism, and nonstrangulating intestinal ischemia that is observed in horses with S. vulgaris infection.     

Thromboelastography in healthy, sick non-septic and septic neonatal foals

Objectives To evaluate citrated recalcified thromboelastography (TEG) in healthy newborn foals, and to determine intra‐assay, inter‐individual and intra‐individual (at 12 h, 24 h and 7 days after birth) variations. Additionally, to compare TEG variables, haematological values and conventional coagulation profiles from healthy, sick non‐septic, and septic foals. Design Prospective study. Methods The study group comprised 18 healthy, 15 sick non‐septic and 17 septic foals. Two citrated (3.2%; 1 : 9 anticoagulant : blood ratio) blood samples were submitted for haemostatic evaluation using a TEG analyser and conventional coagulation profile. TEG values (R time (R), K time (K), angle (α), maximum amplitude (MA) and G value (G)), complete blood count (CBC) and conventional coagulation profile (prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen concentration (Fib) and antithrombin (AT)) were evaluated. Signalment, presenting complaint, sepsis scores, blood culture results and outcome were taken from the medical records of the sick foals. Results Mean values ± SD for TEG variables in healthy neonatal foals were: R = 11.82 ± 5.35 min, K = 3.06 ± 1.34 min, α= 51.19 ± 12.66 degrees, MA = 55.06 ± 6.67 mm and G = 6361 ± 1700 dyn/cm². Mean coefficients of variation for intra‐assay/inter‐individual/intra‐individual in healthy foals were: R = 3.5/45.2/43.1%; K = 5.3/58.7/28.7%; α= 1.5/24.7/11.9%; MA = 0.3/12.1/6.1%; G = 1.6/26.7/14.7%. Septic foals had significantly greater α, MA and G values than sick non‐septic foals, and significantly greater MA and G than healthy foals, changes that are consistent with hypercoagulability. Weak correlations were detected between TEG variables and haematological or haemostatic values. Conclusions TEG could be used to provide additional information about the haemostatic system in equine neonates.     

Antimicrobial-induced endotoxin and cytokine activity in an in vitro model of septicemia in foals

OBJECTIVE: To determine which antimicrobials that are used to treat neonatal foals with septicemia attributable to Escherichia coli will minimize endotoxin release from bacteria and subsequent activity of inflammatory mediators while maintaining bactericidal efficacy. SAMPLE POPULATION: Blood samples from 10 healthy foals. PROCEDURE: Escherichia coli isolates A and B were isolated from 2 septicemic foals, and minimal inhibitory concentrations (MIC) were determined for 9 antimicrobials. Five of these antimicrobials were tested in vitro at 2 and 20 times their respective MIC. Whole blood or mononuclear cells grown in tissue-culture media were incubated with 105 colony-forming units of E. coli and each antimicrobial or saline (0.9% NaCl) solution. After 6 hours, number of viable bacteria remaining was determined, and supernatant was tested for endotoxin and tumor necrosis activity. RESULTS: Testing in whole blood was compromised by bactericidal effects of the blood itself. In mononuclear cell suspensions, each antimicrobial significantly reduced the number of viable bacteria to low or undetectable amounts. Antimicrobials did not differ significantly in efficacy of bacterial killing. Amikacin used alone or in combination with ampicillin resulted in significantly less endotoxin activity than did ampicillin, imipenem, or ceftiofur alone. There was a correlation between TNF-alpha and endotoxin activity. CONCLUSIONS AND CLINICAL RELEVANCE: Aminoglycosides appear less likely to induce endotoxemia and TNF-alpha synthesis during bactericidal treatment of E. coli septicemia, compared with beta-lactam antimicrobials. Use of ampicillin, imipenem, or ceftiofur in the treatment of septicemic neonatal foals should be accompanied by appropriate treatment for endotoxemia.     

Fibrin deposits and organ failure in newborn foals with severe septicemia

Background: Septicemia in human neonates frequently is complicated by activation of the coagulation system, disseminated intravascular coagulation (DIC) and multiple organ failure syndrome, which may contribute to high mortality. In adult horses with DIC, the lung has been the organ most frequently affected by fibrin deposits. In addition, in vivo studies suggest that hemostatic mechanisms may be immature in foals <1‐day old. Hypothesis: Newborn foals with severe septicemia have fibrin deposits in their tissues independently of their age, and these fibrin deposits are associated with organ failure. Animals: Thirty‐two septic and 4 nonseptic newborn foals euthanized for poor prognosis. Methods: Tissue samples (kidney, lung, and liver) collected on postmortem examination were stained with phosphotungstic acid hematoxylin (PTAH) and immunohistochemistry (IHC) for blind histologic examination. A fibrin score (grades 0–4) was established for each tissue sample and for each foal. Medical records were reviewed for assessing clinical evidence of organ failure during hospitalization. Results: Fibrin deposits were found in most septic foals (28/32 when using IHC and 21/32 when using PTAH), independently of the age of the foal. The lung was the most affected tissue (97% of the septic foals). Additionally, organ failure was diagnosed in 18/32 septic foals (8 with respiratory failure, 14 with renal failure), although a statistical association with severe fibrin deposition was not identified. Conclusions and Clinical Importance: Nonsurviving septic foals have fibrin deposits in their tissues, a finding consistent with capillary microthrombosis and DIC.     

Synovial fluid D-dimer concentration in foals with septic joint disease

Background: Increased synovial fibrinolytic activity (detected by increases in synovial D‐Dimer concentrations) has been observed in different joint diseases in humans and adult horses, presumably in order to minimize fibrin deposition within the joint and thus avoid its detrimental effects. Objective: To investigate fibrinolytic pathway activation in joint sepsis in foals by measuring synovial D‐Dimer concentrations. Animals: Eighteen septic foals with septic joints, 9 septic foals without septic joints, 9 systemically healthy foals with septic joint, and 3 controls are included. Methods: Prospective observational clinical study of foals admitted for septic arthritis. Synovial D‐Dimer concentration and routine synovial fluid analysis were performed. Diagnosis of joint sepsis was made whenever synovial total nucleated cell count was >30,000 cells/μL, synovial total protein >4 g/dL, and neutrophil percentage of >80%, or synovial fluid culture resulted positive. Results were compared among groups by general lineal models. Results: Synovial D‐Dimer concentration was significantly (P < .001) higher in the foals with septic joints compared with foals without joint disease (P < .001). Conclusions and Clinical Importance: Septic joint disease is associated with a marked increase of synovial D‐Dimer concentration (marked activation of the fibrinolytic activity) within the affected joint. Although further studies are needed, the measurement of synovial D‐Dimer concentration may be considered a complementary diagnostic marker of septic joint disease.     

Prospective Evaluation of Coagulation in Critically Ill Neonatal Foals

Background: Coagulopathy is a potentially underrecognized complication of sepsis and septic shock in critically ill neonatal foals.
Hypothesis: Critically ill neonatal foals have abnormalities in coagulation that are associated with disease severity and outcome.
Animals: Foals <72 hours old admitted to a neonatal intensive care unit.
Methods: Prospective, observational study. Blood was collected at admission, 24, and 48 hours for platelet count, prothrombin time, activated partial thromboplastin time, antithrombin activity and concentrations of fibrin degradation products, and fibrinogen in plasma from all foals.
Results: Sixty-three foals were enrolled and classified as Septic Shock (12), Septic (28), and Other (23). At least 1 abnormal value was found in 18/28 (64%) samples from the Septic Shock group, 66/85 (78%) from the Septic group, and 30/59 (51%) from the Other group ( P = .01). Coagulopathy (3 or more abnormal values) was present in 7/28 (25%) samples in the Septic Shock group, 14/85 (16%) samples in the Septic group, and 3/59 (5%) samples in the Other group ( P = .0028). Clinically detectable bleeding occurred in 8/12 (67%) Septic Shock cases, 11/28 (39%) Septic cases, and 3/23 (13%) Other cases ( P = .009). Foals in Septic Shock were 12.7 times more likely to have clinical evidence of bleeding than those in the Other group (95% CI 2.3–70, P = .004). Treatment with fluids or plasma did not have a detectable effect on coagulation values.
Conclusions and Clinical Importance: Coagulopathy commonly occurs in critically ill neonatal foals, especially those with sepsis and septic shock.     

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 principal horses. Compared with control horses, postoperative peritoneal fluid from horses undergoing laparotomy had significantly increased antithrombin-III activity at 12 and 72 hours, alpha-2 antiplasmin activity at 24 hours, fibrin degradation product concentrations at 6, 12, 24, 72, 96, and 144 hours, plasminogen activity at 6, 12, 24, 48, 72 and 96 hours, and protein-C activity at 12, 24, 72, and 96 hours. There were no significant changes in the peritoneal fibrinogen concentration in principal horses. Plasma plasminogen activity was significantly decreased at 24 hours after surgery in principal horses, compared with controls. Changes were minimal in the remaining plasma coagulation/fibrinolytic components of horses undergoing laparotomy. Plasma and peritoneal fluid values of anesthetized control horses did not change.     

Hemostatic abnormalities in equine colic

Hemostatic profiles were determined in 30 horses with clinical colic. Blood samples were obtained at the time of the animal's admission, and the following hemostatic tests were done: blood platelet count, plasma fibrinogen, plasma antithrombin, prothrombin time, partial thromboplastin time, thrombin time, protamine sulfate test for soluble fibrin monomer, and fibrin-fibrinogen degradation products. The patients were categorized in retrospect, according to the cause of the colic: group 1--colic associated with colitis and/or severe diarrhea, group 2--colic associated with torsion or obstruction of the intestine, and group 3--colic associated with impaction of the intestine or the presence of enteroliths. Of the 30 horses with colic, 28 had at least 1 abnormality in their coagulogram--the most frequent abnormalities being high plasma fibrinogen concentration, high circulating soluble fibrin monomer, or a long partial thromboplastin time or thrombin time. The horses in group 1 seemed to have the most severe coagulopathies, as indicated by the average number of demonstrable abnormalities. The horses in group 3 showed the fewest abnormalities--usually a high plasma concentrations of fibrinogen and/or soluble fibrin monomer. The results indicated that hemostatic abnormalities are not uncommon in horses with gastrointestinal disease and colic--the degree of severity depending to some extent on the cause of the colic.     

Abnormal Hemostatic Profiles and Gastric Necrosis in Canine Gastric Dilatation-Volvulus

Hemostatic profiles (prothrombin time, activated partial thromboplastin time, fibrinogen concentration, fibrin degradation product concentration, platelet count, and antithrombin III activity) were acquired prospectively in 20 dogs with a diagnosis of gastric dilatation-volvulus. Eighteen dogs had abnormal results of one or more hemostatic test, including eight dogs that had hemostatic profiles consistent with a diagnosis of disseminated intravascular coagulation. During surgery, or at necropsy, the dogs' stomachs were evaluated for gross abnormalities, and lesions were graded subjectively as mild, moderate, or severe. Eight dogs had mild gastric lesions, five had moderate lesions, and seven had severe changes indicating gastric necrosis. Seventy percent (7/10) of the dogs with two to six abnormal hemostatic test results had gastric necrosis, whereas none of the 10 dogs with no or one abnormality had gastric necrosis (p < .001). A multiple linear regression equation, based on fibrin degradation product concentration, activated partial thromboplastin time, and antithrombin III activity was derived to predict gastric necrosis. This equation correctly identified gastric necrosis with 86% sensitivity, 100% specificity, 100% positive predictive value, and 93% negative predictive value.     

Acute thrombosis of limb arteries in horses with sepsis: five cases (1988-1998)

A hypercoagulable condition and poor perfusion to distal extremities might occur during equine endotoxaemic or septic shock, which could cause thrombosis of limb arteries. In our review, thrombosis occurred in neonatal foals in association with gram-negative bacteraemia. In 3 older foals and adults, thrombosis was associated with inflammatory bowel disease, diarrhoea and toxaemia. All patients had been treated with broad-spectrum antibiotics, nonsteroidal antiinflammatory drugs and i.v. crystalloid solutions. Two horses received i.v. hyperimmune plasma. A generalised coagulopathy was not suspected prior to clinical signs of distal limb necrosis, although thrombocytopenia occurred in 4 of the 5 cases at the time of, or shortly before, thrombosis. Thrombocytopenia, possibly due to platelets adherence to exposed subendothelial collagen, which induces contact activation of the intrinsic coagulation pathway, has been described in endotoxaemic horses and foals with gastrointestinal infectious or inflammatory diseases and disseminated intravascular coagulation. Activation of procoagulants by endotoxins, decreased blood flow to the limbs and endothelial damage, may have been responsible for a hypercoagulable condition leading to thrombosis in these 5 cases. The 3 enterocolitis patients may have had increased risk of thrombosis because of loss of antithrombin III, haemoconcentration and acidosis.