L. Monreal

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.

Peritoneal d-Dimer Concentration for Assessing Peritoneal Fibrinolytic Activity in Horses with Colic

BACKGROUND Plasma D-dimer concentration is a useful marker to assess systemic coagulation and fibrinolytic activities in humans, dogs, and horses. Peritoneal fibrinolytic activity increases in horses with colic, especially in horses with endotoxin in the peritoneal fluid. HYPOTHESIS/OBJECTIVES Peritoneal D-dimer concentration can be used to assess peritoneal fibrinolytic activity in horses with severe gastrointestinal (GI) disorders and altered peritoneal fluid. ANIMALS Two hundred and twenty-one colic horses and 15 control horses. METHODS Prospective observational clinical study. Blood and peritoneal fluid were collected on admission. Horses were grouped according to diagnosis, peritoneal fluid analysis, and outcome. Peritoneal D-dimer concentration was determined, together with peritoneal tissue-plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) activities. Plasma D-dimer concentration also was measured. RESULTS Peritoneal D-dimer concentration was significantly higher in all colic groups compared with controls, and in horses with enteritis, peritonitis, and ischemic disorders compared with horses with large intestinal obstructions. Peritoneal D-dimer concentration was significantly higher in horses with altered peritoneal fluid (modified transudate and exudate) compared with horses with normal peritoneal fluid analysis. Plasma D-dimer concentration also was significantly higher in the peritonitis group, and in horses with altered peritoneal fluid analysis. Peritoneal and plasma D-dimer concentrations also were significantly higher in nonsurvivors. Peritoneal d-dimer concentration was significantly correlated with decreased peritoneal t-PA activity and increased peritoneal PAI-1 activity. CONCLUSIONS AND CLINICAL IMPORTANCE Peritoneal D-dimer concentration is markedly higher in severe GI disorders, and it can be used to assess peritoneal fibrinolytic activity in horses with colic.

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.

Association between hypercoagulability and decreased survival in horses with ischemic or inflammatory gastrointestinal disease.

BACKGROUND 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). HYPOTHESIS/OBJECTIVES 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. ANIMALS 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). METHODS Prospective, observational clinical study. TEG profiles of 30 horses with ischemic or inflammatory GI disease were obtained on admission and 48 hours after admission, and these were compared with profiles from 30 horses with nonischemic or inflammatory GI disease and 30 healthy controls. Prothrombin time (PT), activated partial thromboplastin time (aPTT), antithrombin activity (AT), and D-Dimer concentrations were also determined in horses with GI disease. RESULTS Horses with ischemic or inflammatory GI disease had shorter R times compared with healthy horses (14.8±8.3 versus 22.8±12 minute; P=.011). However, changes were subtle and TEG profiles did not resembled those obtained from animals or humans presumed to be hypercoagulable. Although conventional coagulation testing supported the presence of HC (decreased AT and increased D-Dimer concentrations), TEG and coagulation abnormalities were rarely found in the same horses and the methods were not statistically related. CONCLUSIONS AND CLINICAL IMPORTANCE There is evidence of HC in horses with GI disease but techniques for diagnoses require refinement.

Association of Admission Plasma D‐Dimer Concentration with Diagnosis and Outcome in Horses with Colic

BACKGROUND Coagulopathies detected in horses with gastrointestinal problems seem to be associated with poor outcome. Plasma D-Dimer concentration is a sensitive test for assessing coagulopathies. HYPOTHESIS Plasma D-Dimer concentration tested on admission is related to diagnosis and outcome in horses with colic. ANIMALS Four hundred and ninety three horses referred for evaluation of abdominal pain. METHODS Prospective observational clinical study. Horses were grouped according to diagnosis (medical and surgical intestinal obstructions, ischemic disorders with and without intestinal resection, enteritis, peritonitis), outcome (survivors, nonsurvivors), and number of coagulopathies (normal profile, 1 or 2 coagulopathies, subclinical disseminated intravascular coagulation [DIC]). Blood samples were collected on admission and plasma D-Dimer concentration, clotting times (PT and aPTT), and antithrombin activity were determined. Positive likelihood ratios (LR+) were calculated for evaluation of D-Dimer cut-off values, which were later tested in a logistic regression model. RESULTS Horses with enteritis or peritonitis had significantly (P<.001) higher plasma D-Dimer concentrations and more severe coagulopathies on admission than horses with other diagnoses. Nonsurvivors also had significantly (P<.001) higher plasma D-Dimer concentrations at presentation than did survivors, and those horses with subclinical DIC on presentation had an odds ratio (OR) 8.6 (95% confidence interval [CI], 3.3-22.5, P<.001) for nonsurvival. Finally, D-Dimer concentrations>4,000 ng/mL had a LR+ of 5.9 and an OR 8.8 (95% CI, 4.5-17.1, P<.001) for nonsurvival. CONCLUSION AND CLINICAL IMPORTANCE Plasma D-Dimer concentration measured on admission can be used to facilitate diagnosis and outcome prediction in horses with colic. A potential cut-off value for nonsurvival was found at approximately 4,000 ng/mL.

Acid-base imbalances during a 120 km endurance race compared by traditional and simplified strong ion difference methods.

REASONS FOR PERFORMING STUDY Acid-base disturbances are traditionally assessed using the Henderson-Hasselbach equation. The simplified strong ion approach describes more accurately the complex acid-base and electrolyte abnormalities present in endurance horses. OBJECTIVE To describe acid-base and electrolytes changes in fit horses competing in a FEI*** 120 km endurance race and to compare the traditional vs. strong ion approaches. METHODS Thirty horses were initially enrolled in the study. Venous blood samples were obtained before the race (n = 25), at the second (n = 29; 65.4 km) and third vet-gates (n = 23, 97.4 km) and upon race completion (n = 17). Blood gas analysis was performed to determine pH, PCO(2), PO(2), Na(+), K(+) and iCa(++), and calculate HCO(3)(-), base excess and tCO(2). Packed cell volume and total protein, globulin, albumin, lactate, phosphate, glucose and creatinine concentrations, as well as muscle enzymes activities, were also determined. Calculated variables included strong ion difference (SIDm), strong ion gap (SIG) and nonvolatile buffer concentration (A(tot)). A longitudinal linear model using the general estimating equation methodology was used for statistical analysis. RESULTS Mild but significant increases in PCO(2), SIDm, lactate, plasma protein, globulins and A(tot), as well as a decrease in potassium concentrations were observed from the second vet-gate to race finish when compared to prerace values (P < 0.05). Using the strong ion approach, 67% samples showed acid-base disturbances vs. 70% when using the traditional method, but their interpretations only matched in 24% of measurements. CONCLUSIONS A complex acid-base imbalance characterised by a mild strong ion alkalosis (hypochloraemia attenuated by hyperlactataemia), nonvolatile buffer acidosis and compensatory mild respiratory acidosis were present in most horses, although pH did not significantly change during a 120 km endurance race. The strong ion approach to interpretation of acid-base balance should be favoured over the traditional approach in endurance horses, given the frequent and complex alterations in PCO(2), SIDm and A(tot) during a race.

Evaluation of thrombin-antithrombin complexes and fibrin fragment D in carbohydrate-induced acute laminitis.

Carbohydrate-induced laminitis has been associated with decreased platelet survival, decreased blood flow to the hoof wall and with the deposition of platelets and microthrombi within venules in the dermal laminae. To evaluate further the systemic prothrombotic events occurring in the prodromal stages of laminitis, plasma samples from control and laminitis-affected ponies and horses were tested for the presence of thrombin-antithrombin (TAT) complexes and fibrin fragment D (D-dimer). No statistically significant differences between the control and laminitis-affected animals were observed for either the D-dimer or the TAT complexes. Few of the values for individual animals exceeded the reference ranges for control animals. These data indicate that the prothrombotic events observed in carbohydrate-induced laminitis may not be associated with systemic activation of the coagulation or fibrinolytic systems.

Enteral fluid therapy in 108 horses with large colon impactions and dorsal displacements

To assess the effect of enteral fluid therapy (EFT) in horses with colic, 78 adult horses with colon impactions and 30 with left dorsal colon displacements received an isotonic electrolyte solution via a nasogastric tube at a rate of 8 to 10 l every two hours until resolution of clinical signs. Clinical progression was monitored closely, and plasma biochemistry was evaluated before, during and after treatment. Volume of fluids, time to resolution, and outcome were also recorded. EFT was well tolerated by 102 of 108 horses and was an effective method to resolve 99 per cent of colon impactions and 83 per cent of displacements. For both groups, the mean (sd) time to resolution was 20.2 (5.2) hours and the volume of fluid administered was 118.6 (34.5) l. No relevant abnormalities were observed in most plasma biochemistry parameters during treatment, except for a mild haemodilution effect in 63 per cent of horses.

Coagulopathies in Horses with Colic

The most common coagulopathy in horses with colic is a hypercoagulable state associated with disseminated intravascular coagulation. The intensity of this coagulopathy depends on the severity and duration of the gastrointestinal lesion, with the ischemic and inflammatory problems and peritonitis being the most frequently affected by coagulopathies. Early initiation of prophylactic therapy significantly reduces the severe hypercoagulable state in horses with intestinal conditions which are recognized to be at high risk for disseminated intravascular coagulation. In addition to the systemic coagulopathy observed in horses with colic, a peritoneal coagulopathy independent from that occurring in blood has been observed, and its recognition and assessment may have clinical usefulness in the diagnosis of the gastrointestinal diseases and outcome.

Heparin-Related Osteoporosis in Rats

In an animal model, the effect of a high dose of conventional heparin (2 IU/g s.c. twice a day) and a low-molecular-weight heparin (LMWH; Fragmin, 1 anti-Xa U/g once a day) was compared with that of placebo on the mineral bone mass in the femur of rats. After 33 days of treatment no differences were found in the weight of the femur. But heparin-treated rats exhibited a lower density (1,249 ± 0.046 g/ml as compared with that in control rats (p = 0.00007) and also in LMWH-treated rats (p = 0.001). Similarly, statistically significant differences have been found in ash contents. They were higher in control rats than in heparin-treated rats (p = 0.0002), and also slightly higher than in LMWH-treated rats (p = 0.01). Our findings suggest that LMWH may have a lower osteopenic effect than that of conventional heparin.