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)     

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)     

Changes in coagulation and markers of fibrinolysis in horses undergoing colic surgery

Activation of coagulation can be frequently found in horses with colic. However, it has also been demonstrated as a sequela of surgical trauma alone in humans. The purpose of the present study was to determine changes in coagulation and fibrinolysis in horses that underwent colic surgery and to evaluate whether these changes were secondary to the colic or the surgery and wound healing. Thirty horses that underwent colic surgery with uncomplicated recovery were included. Ten horses with a Forssell's procedure served as control group with a standardized surgical trauma. Besides daily physical examinations during the observation period of 10 days, activated partial thromboplastin time (aPTT), prothrombin time and thrombin time as well as fibrin monomer (FM), D-Dimer (DD) and antithrombin (AT) III were determined. Compared with the control group the aPTT was the only standard coagulation test that was significantly prolonged before and after the event of colic surgery. After surgery, hyperfibrinogenaemia occurred in all groups. In colic groups FM and DD concentrations were within reference range at admission,and were significantly greater than in control horses after surgery. AT III activity decreased after colic surgery, but did not change in the control group. It was concluded that an activated coagulation state after colic surgery has to be expected, resulting not only from the colic disease, but also from the event of surgery.     

Disseminated intravascular coagulation in a horse with postpartum ulcerative colitis and laminitis

Hemostatic studies were conducted on a five year old Belgian mare presented two days postpartum with colic and laminitis that was unresponsive to treatment.

The mare was moderately thrombocytopenic with plasma fibrinogen levels more than twice that of a normal control horse. Platelet function as evaluated by aggregometry indicated that the circulating platelets were markedly hyporesponsive. Activated partial thromboplastin times and prothrombin times were prolonged. Para-coagulation tests (protamine sulfate and ethanol gelation) were strongly positive and fibrin degradation products were significantly elevated in the serum.

The laboratory data suggested that the clinical bleeding was the result of the development of disseminated intravascular coagulation. The data were compatible with intravascular activation of the clotting mechanism, consumption of hemostatic factors, inhibition of platelet function and enhanced stimulation of the fibrinolytic mechanism.

This report illustrates the complexity of the hemostatic abnormalities associated with pathological overactivation of the hemostatic mechanism. Factors such as tissue thromboplastins and/or endotoxins can stimulate disseminated intravascular coagulation, particularly during pregnancy or in the early postpartum period when a physiological “hypercoagulable” state already exists.

     

The coagulation system in horses with colic

Colic in horses very often induces changes in the coagulation system causing the development of disseminated intravascular clotting. It is promoted by blood concentration and an increase in exposition of coagulation activators with a simultaneous decrease in coagulation inhibitors activity, mainly antithrombin III. Progressing blood platelets aggregation supports production of microthromboses and plugging capillary vessels. The progression of this processes causes complications in basic disease and becomes the reason for therapeutic failure. Determination of coagulation system indexes such as the number of platelets, prothrombin time, activated partial thromboplastin time, thrombin time, concentration of fibrinogen and fibrinogen degradation products, and D-dimmer and antithrombin III contents enables diagnosis and facilitates appropriate therapy of colic in horses.     

Influence of an omega-3 fatty acid-enriched ration on in vivo responses of horses to endotoxin.

Because certain inflammatory processes are dependent on the fatty acid composition of the cellular membrane, dietary manipulations that replace omega-6 fatty acids with omega-3 fatty acids may modify inflammatory responses. We investigated the effect of supplemental dietary linseed oil, containing the omega-3 fatty acid, alpha-linolenic acid, on in vivo responses of horses to endotoxin. One group of horses (n = 6) was fed a control pelleted ration (0% linseed oil), and another group of horses (n = 6) was fed an 8% linseed oil pelleted ration. After 8 weeks of consuming these rations, all horses were given 0.03 micrograms of Escherichia coli 055:B5 endotoxin/kg of body weight, infused over 30 minutes. Horses were monitored over 24 hours. Compared with baseline values within each ration group, endotoxin infusion caused significant (P less than 0.05) increase in rectal temperature, heart rate, and plasma concentration of thromboxane B2, 6-keto-prostaglandin F1 alpha, and fibrinogen and significant (P less than 0.05) decrease in total WBC count. Compared with baseline values within each ration group, endotoxin infusion failed to cause significant changes in prothrombin, activated partial thromboplastin, thrombin, or whole blood recalcification times, serum concentration of fibrin degradation products, PCV, or plasma total protein concentration. Before and after endotoxin infusion, horses given the linseed oil ration had longer mean whole blood recalcification time and activated partial thromboplastin time than did horses fed the control ration.     

Afibrinogenemia and a circulating antibody against fibrinogen in a Bichon Frise dog

A 1.5-year-old female Bichon Frise dog was evaluated for a life-threatening hemorrhagic condition that occurred after ovariohysterectomy, requiring 4 whole-blood transfusions. A hemostatic profile, including activated clotting time (ACT), one-stage prothrombin time (OSPT), activated partial thromboplastin time (APTT), buccal mucosal bleeding time, and specific assays (heat-precipitation microhematocrit method and electroimmunoassay) for fibrinogen, were performed to investigate the coagulopathy. Clotting times for all tests having a fibrin clot endpoint (ACT, OSPT, APTT) and buccal mucosal bleeding time were prolonged. Plasma fibrinogen was not detected by heat-precipitation microhematocrit method or electroimmunoassay. Using the Ellis-Stransky method, a mixture of patient plasma and normal canine plasma with known fibrinogen content yielded substantially less than the calculated fibrinogen concentration, indicating the presence of an interfering substance. The interferent properties of the patient's plasma were retained following heat precipitation at 56 degrees C indicating the absence of a pyroglobulin or an abnormal fibrinogen molecule. Radial immunodiffusion assay using the patient's plasma and activated thrombin confirmed the existence of an inhibitor to the formation of fibrin. Western blot analysis using the patient's plasma identified an IgG antibody that reacted with the Beta- and gamma- but not the Alpha-subunits of canine fibrinogen. Antibody was detected in samples taken 8, 16, and 68 days after the surgery; peak titers were evident at day 16. These results supported a diagnosis of afibrinogenemia with a circulating antibody inhibitor to fibrin clot formation that developed secondary to blood transfusion.     

Diagnosis of disseminated intravascular coagulation in dogs admitted to an intensive care unit.

OBJECTIVE: To describe and evaluate hemostatic function in critically ill dogs with clinical signs of diseases that predispose to disseminated intravascular coagulation (DIC). DESIGN: Prospective case series. ANIMALS: 59 critically ill dogs (affected dogs) with clinical signs of diseases known to predispose to DIC and 52 clinically normal dogs (control dogs). PROCEDURE: Activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin clotting time (TCT), plasma fibrinogen concentration, serum concentration of fibrin and fibrinogen-related antigens (FRA), and plasma antithrombin III (AT III) activity were determined for all dogs. Results from affected dogs were compared with those of control dogs. In some affected dogs, postmortem tissue specimens were examined for evidence of microvascular thrombosis. A diagnosis of DIC was made by fulfilling at least 3 of the following criteria: 1) abnormal aPTT, PT, or TCT value, 2) low plasma fibrinogen concentration, 3) low plasma AT III activity, 4) high serum FRA concentration, or 5) low platelet count. To evaluate the severity of hemostatic dysfunction, 3 arbitrary categories (mild, moderate, and severe) were proposed. RESULTS: A diagnostic strategy based on moderate hemostatic dysfunction identified DIC in 16 of 59 (27.1%) affected dogs. The AT III activity was < 70% in 15 of 16 dogs with DIC. Microvascular thrombosis was observed in tissue specimens from 7 of 8 affected dogs. Serum FRA and plasma fibrinogen concentrations did not contribute in establishing a diagnosis of DIC. CONCLUSIONS AND CLINICAL RELEVANCE: A diagnosis of DIC can be made when hemostatic dysfunction is moderate in dogs with clinical signs of diseases associated with DIC.     

Correlation of haemostatic abnormalities with tumour stage and characteristics in dogs with mammary carcinoma

Sixty female dogs with untreated mammary carcinoma, comprising equal numbers of dogs in tumour stages I to IV, were evaluated for haemostatic abnormalities using the following tests: platelet count, prothrombin time, activated partial thromboplastin time, thrombin time, plasma activity of factor V, VIII and X, plasma concentration of fibrinogen, fibrin monomers and fibrinogen degradation products, and plasma antithrombin III activity. Two-thirds of all dogs had one or more haemostatic test abnormality of which the likelihood and frequency was increased in those with stage III and IV neoplasia. Haemostatic abnormalities were more frequently observed in dogs which had mammary tumours with distant metastases, extended tumour necrosis, inflammatory carcinomas, tumours fixed to underlying structures, or tumours in which there was penetration of the tumour capsule by tumour cells. As in humans with mammary carcinoma, these haemostatic abnormalities might be used as prognostic indicators, but their clinical importance remains unknown.     

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.     

Study of haemostatic disorders in experimentally induced leishmaniasis in Beagle dogs

Haemostatic alterations in dogs experimentally infected with Leishmania infantumwere studied before and after therapy with meglumine antimonate. Haemostatic function tests including platelet count, collagen-induced platelet aggregation, prothrombin time, activated partial thromboplastin time, thrombin time, plasma fibrinogen determination, and serum fibrinogen/fibrin degradation products concentration were performed. In the course of infection and before treatment, moderate thrombocytopenia (P<0·00001) decreased collagen induced platelet aggregation (P=0·0003), prolonged thrombin time (P=0·0117) and increased fibrinogen/fibrin degradation products were observed. Statistically significant differences of plasma fibrinogen concentration, prothrombin time, and activated partial thromboplastin time were not encountered. Haemostatic parameters returned to normal values after therapy. The results indicate that Leishmania infection may impair haemostasis suggesting induction of disseminated intravascular coagulation (DIC), and that treating dogs in an early stage of infection may potentially avoid the possibility of developing an uncompensated DIC.     

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.     

Evaluation of the effect of storage at -70 degrees C for six months on hemostatic function testing in dogs.

Freezing is a routine method of storage for plasma that is to be used in evaluating certain aspects of hemostatic function in many species. The purpose of this study was to evaluate the effect of storage at -70 degrees C for 6 mo on canine plasma samples. On fresh and frozen plasma from 12 clinically healthy dogs, prothrombin time, activated partial thromboplastin time, thrombin clotting time, fibrinogen determination, antithrombin III activity, fragment D and E assay, and protamine sulfate test were performed. Clinical agreement analysis was utilized to determine the effect of such storage on all assays. Individual differences detected between fresh and frozen samples were all within 2 standard deviations of the mean difference. With the exception of the activated partial thromboplastin time, storing canine plasma at -70 degrees C for 6 mo has no significant effect on hemostatic function, as assessed by these tests.     

Disseminated Intravascular Coagulation in Ponies with Surgically Induced Strangulation Obstruction of the Small Intestine

Total strangulation obstruction (S/O) of the jejuno-ileum was produced in a group of randomly selected ponies. Peripheral blood samples were collected prior to surgery and at 3-hour intervals following obstruction. A coagulation profile consisting of platelet count, fibrinogen titer (FT), prothrombin time (PT), activated partial thromboplastin time (APTT), and serial dilution protamine sulfate test (SDPS) for fibrin monomers (FM) and/or early fibrin degradation products (fdp) was evaluated. The packed cell volume (PCV) and total plasma protein (TPP) were also determined. Concurrent peritoneal fluid samples were assessed grossly. Sham-operated (sham) ponies were treated in a similar manner, excluding the production of a strangulation obstruction of the small intestine. Notable coagulopathies occurred in the S/O group. PT and APTT were increased significantly in samples collected within 6 hours of death. All S/O horses developed strongly positive SDPS reactions, while sham ponies, presurgical S/O ponies, and early S/O postsurgical samples were unremarkable. There were no significant shifts in the fibrinogen titer. Platelet counts were significantly decreased during the final 10% of sampling time in S/O horses. The coagulopathies observed in the S/O ponies appear to be secondary to the pathophysiologic changes produced by the S/O and not related to surgical trauma.     

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.     

Evaluation of secondary haemostasis in canine leishmaniasis

Secondary haemostasis was evaluated in 26 dogs with leishmaniasis and 10 normal dogs by measurements of modified one-stage prothrombin time (m-OSPT), activated partial thromboplastin time (APTT), thrombin time, fibrinogen concentration and fibrin degradation products. There were no significant differences between the groups in the m-OSPT, fibrinogen concentration, or levels of fibrin degradation products. The APTT was significantly (P = 0.006) longer in the infected dogs than in the control group, and in infected dogs with alanine aminotransferase (ALT) activities > 50 U/litre. There was a significant linear regression between ALT and APTT. Thrombin time was significantly (P = 0.003) longer in the infected dogs than in the normal dogs. There were no significant differences between the thrombin times of sick dogs with different levels of creatinine or activities of ALT, or between male and female dogs, whether diseased or normal.     

Effects of aspirin and propranolol alone and in combination on hemostatic determinants in the healthy cat

The effects of aspirin (75 mg orally/average-size cat) and propranolol (5 mg orally every 8 hours/average-size cat) alone and in combination on hemostatic determinants in healthy cats were studied. In cats, aspirin alone did not cause a significant effect in platelet numbers, plasma fibrinogen, activated partial thromboblastin time, prothrombin time, thrombin time, or platelet aggregation response to adenosine diphosphate. Aspirin did, however, significantly reduce the degree of aggregation induced by acid soluble collagen. Propranolol alone or in combination with aspirin did not cause a significant effect on platelet numbers, plasma fibrinogen, activated partial thromboblastin time, prothrombin time, thrombin time, or platelet aggregation in response to acid soluble collagen, adenosine diphosphate, or adrenaline. It was concluded that aspirin alone at the recommended dosage of one-quarter of a 5-grain tablet (1.25 grains or 75 mg) every other day will significantly affect platelet function and may be of value in the prevention of thromboembolic disease in the cat.     

Evaluation of latex agglutination kits for detection of fibrin(ogen) degradation products and D-dimer in healthy horses and horses with severe colic

Background: 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. Objectives: 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 with severe colic. Horses fulfilling predefined laboratory criteria of DIC were enrolled, and their data were subcategorized by survival for analysis. Platelet counts were determined and coagulation panel testing was performed. Serum and plasma FDP concentrations were measured using separate latex agglutination kits. Plasma D‐dimer concentration was measured using 3 latex agglutination kits and a card immunofiltration test. Test sensitivity and specificity results were determined for healthy horses and those with colic. Median test values were compared between colic survivors and nonsurvivors to evaluate the prognostic usefulness of all tests. Results: Performance characteristics varied among assays and kit suppliers. The FDP assays had low sensitivity (<40%), whereas the most accurate D‐dimer kit had 50% sensitivity and 97% specificity. High D‐dimer concentration was the third most common hemostatic abnormality in horses with colic. Median antithrombin (AT) activity was significantly lower and activated partial thromboplastin time (aPTT) was significantly longer in nonsurvivors than survivors. Conclusions: Commercial latex‐agglutination D‐dimer assays might prove useful as adjunctive tests for the diagnosis of DIC in horses with severe colic; however FDP assays are invalid for this purpose. Low AT activity and prolonged aPTT at admission are associated with a poor prognosis in this patient population.     

Use of clinical pathology in evaluation of horses with colic

Clinical pathology is a valuable adjunct to physical examination of cases of colic. The present review considers evaluation of cases of colic for three main purposes: (1) making a prognosis, (2) deciding whether to operate, and (3) making a diagnosis. Blood tests noted to be useful for prognostication were hematocrit, lactate and urea nitrogen concentrations, pH, anion gap, fibrin/fibrinogen degradation products, antithrombin III activity, prothrombin time, and thrombin time. Horses with a poor prognosis often have relative polycythemia, marked lactic acidosis, high anion gap, azotemia, and coagulation abnormalities evidenced by increased fibrin/fibrinogen degradation products, decreased antithrombin III activity, and prolonged prothrombin and thrombin times. The decision to operate is usually a clinical one, supported by relative polycythemia, hyperglycemia, and, possibly, abnormal peritoneal fluid analysis. Diagnosis of the primary problem (causing the colicky signs) is also often based largely on physical examination. However, peritoneal fluid analysis provides worthwhile data, especially in cases of peritonitis or intestinal ischemia and infarction.     

Ontogeny of bovine hemostasis

Ontogeny of selected hemostatic system components was studied in 120 bovine fetuses which had been divided into eight monthly gestational age groups. Fetal blood was subjected to the following tests: platelet count, partial thromboplastin time, prothrombin time, thrombin time, fibrinogen quantitation, and assays for prothrombin and factors V and VIII. Platelet numbers corresponding to adult numbers were in fetal blood at least as early as gestation day 60, and their numbers varied only slightly thereafter. Bovine blood was incapable of in vitro coagulation at gestation day 90, with all samples coagulating by gestation day 150. Fetal coagulation screening test times (partial thromboplastin time, prothrombin time, and thrombin time) shortened during gestation and were near times of adults at birth. Of the four individual coagulation factors tested, only factor VIII reached adult values in the fetus in utero. Amounts of fibrinogen, prothrombin, and factors V and VIII in the neonate exceeded that of normal adult cattle.