C. Cesarini

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.

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.

Metabolic and Endocrine Profiles in Sick Neonatal Foals Are Related to Survival

BACKGROUND Sick neonatal foals suffer from a variety of endocrine and metabolic derangements that may be related to outcome. There are several hepatic and lipid metabolism blood markers that have never been assessed in neonatal foals. OBJECTIVES Assess panel of endocrine and metabolic variables in group of sick and healthy neonatal foals in order to describe their relationship with diagnosis and survival. ANIMALS All neonatal foals referred to Unitat Equina-Fundació Hospital Clínic Veterinari during 3 consecutive foaling seasons and a group of healthy foals. METHODS Observational prospective study. Blood samples were obtained on admission and, when possible, after 24-48 h of hospitalization and immediately before discharge or death. Measured variables were triglycerides, nonsterified fatty acids, glucose, creatinine, urea, γ-glutamyltransferase, glutamate dehydrogenase (GLDH), insulin, cortisol, bile acids, and adrenocorticotropic hormone (ACTH). ACTH/cortisol and glucose/insulin ratios were calculated. RESULTS Urea, creatinine, and cortisol had median concentrations in septic and nonseptic foals 2- to 8-fold higher than in the control group (P < .001). Median ACTH concentration in the septic group was approximately 4 times higher than in nonseptic and control foals (P < .001). ACTH/cortisol ratio was significantly lower in sick foals compared to control foals (P < .001). A score was designed including creatinine, GLDH, and cortisol. When ≥ 2 of these variables were altered (P < .001), the foal had 32 times more risk of dying (OR, 31.7; 95% CI, 7.7-130.3). CONCLUSIONS AND CLINICAL IMPORTANCE Plasma creatinine, GLDH, and cortisol should be determined in sick newborn foals on admission because of their association with survival.

Uveal Inflammation in Septic Newborn Foals

BACKGROUND Septicemia in humans is described as a leading cause of uveitis, which eventually can induce blindness. HYPOTHESIS/OBJECTIVES Uveal inflammatory findings could be related to sepsis severity in newborn foals and might be used as an indirect indicator for survival. ANIMALS Seventy-four septic foals, 54 nonseptic foals, and 42 healthy foals. METHODS Prospective observational clinical study. A detailed blinded, ophthalmic examination was performed by boarded ophthalmologists on all admitted newborn foals. Foals were grouped as septic (when blood culture resulted positive or the sepsis score was > or =14), nonseptic, and controls. Based on blood culture results, the septic group was subdivided into bacteremic and nonbacteremic foals. RESULTS Blood culture was performed in 62/74 septic foals, from which 35 (56%) were bacteremic and 27 (44%) were non-bacteremic. Anterior uveitis was diagnosed in a significantly (P < .005) higher number of septic/bacteremic foals (14/35, 40%) than in septic/nonbacteremic foals (5/27, 19%), nonseptic foals (4/54, 7%), and control foals (0%). Anterior chamber fibrin was only observed in 4/14 (29%) septic/bacteremic foals with anterior uveitis. Anterior uveitis was also associated with posterior uveitis in 6/35 (19%) septic/bacteremic foals. The diagnosis of uveitis was related to nonsurvival (P = .001, odds ratio = 6.2, 95% confidence interval = 2.1-18.2). CONCLUSIONS AND CLINICAL IMPORTANCE Anterior uveitis is highly prevalent in septic newborn foals, especially in those with a positive blood culture, and it should be considered as a survival prognostic factor.

Low-Molecular-Weight Heparin Dosage in Newborn Foals

BACKGROUND Heparin is used in humans as prophylaxis of hypercoagulable states and disseminated intravascular coagulation (DIC). However, babies need a higher heparin dose than do adults. Septic neonate foals are at high risk of hypercoagulable state and DIC, and there is limited objective information about heparin dose for equine neonates. OBJECTIVE To assess whether neonate foals require higher dosages of low-molecular-weight heparin (LMWH) than adults. ANIMALS Eighteen healthy and 11 septic neonate foals. METHODS Experimental and clinical studies. Firstly, healthy foals were randomly distributed in 2 groups, 1 receiving 50 IU/kg SC of dalteparin and the 2nd group receiving 100 IU/kg SC of dalteparin, once daily for 3 days. Blood samples were collected before and 3, 6, 27, and 51 hours after the 1st LMWH administration. Plasma antifactor-Xa activity was measured, together with hemostatic and hematologic parameters used to assess the risk of bleeding. Subsequently, septic foals were treated blindly either with placebo (saline) or 100 IU/kg of dalteparin for 3 days. Plasma antifactor-Xa activity and other hemostatic parameters were determined before and after treatment. RESULTS Plasma antifactor-Xa activity in healthy foals was below prophylactic activity when using the adult dosage (50 IU/kg), whereas prophylactic activities were achieved when using the double dosage (100 IU/kg). No hemorrhagic events and erythrocyte-related complications were observed with either dosage. In the clinical study, only 4/6 septic foals had plasma antifactor-Xa activity adequate for prophylaxis. CONCLUSIONS AND CLINICAL IMPORTANCE Equine neonates require higher dosages of LMWH compared with adults to reach prophylactic heparinemia.

Progression of plasma D-dimer concentration and coagulopathies during hospitalization in horses with colic

OBJECTIVE To assess the progression of plasma D-dimer concentrations and coagulation status in horses with different types of colic. DESIGN Prospective clinical observational study performed between March 2004 and September 2008. SETTING Veterinary university teaching hospital. ANIMALS Horses admitted and treated for colic and hospitalized for >48 hours were considered. Animals were classified by diagnosis into medical obstructive conditions (MO), surgical obstructive conditions (SO), inflammatory conditions, and ischemic lesions (IS). INTERVENTIONS Three blood samples were obtained from each horse (admission, at 24-48 h [or after surgery] and upon discharge). For each sample, plasma D-dimer concentration, prothrombin time, activated partial thromboplastin time, antithrombin activity, and the presence of subclinical disseminated intravascular coagulation were determined. MEASUREMENTS AND MAIN RESULTS When median plasma D-dimer concentration values at admission and after 24-48 hours were compared, they were different but stable in horses with MO (1.29-1.95 nmol/L) and inflammatory conditions (5.70-6.69 nmol/L). However, 10-fold and 5-fold increases were observed, respectively, in SO (2.08 to 16.38 nmol/L) and IS (3.08 to 15.91 nmol/L) in the postoperative period. By 24-48 hours, the percentage of horses with coagulopathy increased in most groups (MO, 43 to 58%; SO, 50 to 96%, IS, 53 to 90%). By the time of discharge, 87% of horses with SO problems and 89% of horses with IS still had some form of coagulopathy documented. CONCLUSIONS Throughout hospitalization, horses with MO problems had less severe coagulopathy and lower plasmatic D-dimer concentrations compared to other groups of horses. On admission, most horses with inflammatory conditions presented with coagulopathy. At 24-48 hours of hospitalization and following surgery, the hemostatic profile can differ markedly when compared to admission values.

Parallel testing of plasma iron and fibrinogen concentrations to detect systemic inflammation in hospitalized horses

Objectives To determine if plasma iron concentration is different between horses with and without systemic inflammation (SI) and to assess the accuracy for the detection of SI by assaying plasma iron and fibrinogen concentrations, individually or combined. To assess the prognostic value of plasma iron concentration and to describe the progression of plasma iron and fibrinogen concentrations during hospital follow-up, and its relation to SI and survival. Design Prospective observational study evaluating plasma iron and fibrinogen. Setting University veterinary teaching hospital. Animals Equine patients greater than 30 days of age. Interventions None. Measurements and Main Results Plasma iron and fibrinogen concentration was prospectively determined in hospitalized horses. Horses were classified into 2 groups: SI and non-SI. Horses were also classified according to clinical outcome. A group of control healthy horses was also included. A total of 135 horses were included in the study. Plasma iron concentration was significantly lower and fibrinogen concentration was higher in the SI group. Nonsurvivors had a mean plasma fibrinogen concentration significantly higher than survivors. The combination of plasma iron and fibrinogen has a high degree of specificity, sensitivity, and accuracy for the detection of SI in horses. Follow-up measurements were obtained in 48 horses. Surviving horses normalized plasma iron concentration during follow-up examination whereas nonsurviving horses had persistently low plasma iron concentrations. Conclusions Plasma iron concentration alone is an accurate marker of SI in hospitalized horses. Alteration of both plasma iron and fibrinogen concentrations improves the specificity and positive predictive value for diagnosis of SI. Alteration of either one of both increases sensitivity and negative predictive value. Surviving horses normalized plasma iron concentrations during follow-up period. The combination of plasma iron and fibrinogen concentrations may help in the detection of SI. Follow-up of plasma iron concentrations may provide useful prognostic information.OBJECTIVES To determine if plasma iron concentration is different between horses with and without systemic inflammation (SI) and to assess the accuracy for the detection of SI by assaying plasma iron and fibrinogen concentrations, individually or combined. To assess the prognostic value of plasma iron concentration and to describe the progression of plasma iron and fibrinogen concentrations during hospital follow-up, and its relation to SI and survival. DESIGN Prospective observational study evaluating plasma iron and fibrinogen. SETTING University veterinary teaching hospital. ANIMALS Equine patients greater than 30 days of age. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Plasma iron and fibrinogen concentration was prospectively determined in hospitalized horses. Horses were classified into 2 groups: SI and non-SI. Horses were also classified according to clinical outcome. A group of control healthy horses was also included. A total of 135 horses were included in the study. Plasma iron concentration was significantly lower and fibrinogen concentration was higher in the SI group. Nonsurvivors had a mean plasma fibrinogen concentration significantly higher than survivors. The combination of plasma iron and fibrinogen has a high degree of specificity, sensitivity, and accuracy for the detection of SI in horses. Follow-up measurements were obtained in 48 horses. Surviving horses normalized plasma iron concentration during follow-up examination whereas nonsurviving horses had persistently low plasma iron concentrations. CONCLUSIONS Plasma iron concentration alone is an accurate marker of SI in hospitalized horses. Alteration of both plasma iron and fibrinogen concentrations improves the specificity and positive predictive value for diagnosis of SI. Alteration of either one of both increases sensitivity and negative predictive value. Surviving horses normalized plasma iron concentrations during follow-up period. The combination of plasma iron and fibrinogen concentrations may help in the detection of SI. Follow-up of plasma iron concentrations may provide useful prognostic information.

Acid base imbalances in ill neonatal foals and their association with survival.

Reasons for performing study: Acid‐base imbalances observed in human paediatric patients are associated with outcome. Likewise, neonatal foals may have different acid‐base imbalances associated with diagnosis or prognosis. Objectives: To determine acid‐base imbalances by the quantitative method in ill neonatal foals and assess their association with diagnosis and prognosis. Study design: Observational prospective clinical study. Methods: This study included 65 ill neonatal foals (32 septic, 33 nonseptic) admitted to an equine referral hospital from 2005 to 2011with acid‐base parameters determined on admission and a control group of 33 healthy neonatal foals. Blood pH, pCO2, sodium, potassium, chloride, L‐lactate, albumin and phosphate concentrations were determined. Bicarbonate, globulin, measured strong ion difference (SIDm), nonvolatile weak buffer concentrations (Atot), base excess and its components were calculated. Analysis of covariance (ANCOVA) and multiple linear regression statistical analyses were performed. Results are summarised as mean ± s.d. for normally distributed variables and median [25–75th percentiles] for non‐normally distributed ones. Results: A total of 63% of ill foals had respiratory alkalosis and 58.5% had SIDm acidosis. The combination of both alterations was detected in 21 of 65 ill foals and abnormal pH was found in 24 of 65. Compared with healthy foals, ill foals had significantly lower SIDm (nonseptic 31.6 ± 6.3 [P<0.01] and septic 32.0 ± 6.4 [P<0.01] vs. control 40.3 ± 3.1 mmol/l), potassium (nonseptic 3.5 [3.3–3.8; P<0.01] and septic 3.6 [3.2–4.3; P = 0.01] vs. control 4.2 [3.8–4.5] mEq/l) and higher L‐lactate (nonseptic 5.1 ± 4.2 [P = 0.01] and septic 5.0 ± 3.7 [P = 0.03] vs. control 2.5 ± 1.3 mmol/l). Significantly higher L‐lactate and venous pCO2 were found in nonsurviving (6.4 ± 3.5 mmol/l [P = 0.04] and 51 ± 13 mmHg [P<0.01]) compared with surviving foals. Conclusions: The most common acid‐base imbalances observed in ill foals were respiratory alkalosis, SIDm acidosis or mixed respiratory alkalosis with strong ion acidosis. Increased venous pCO2 and blood L‐lactate concentration were associated with poor outcome.

Association Between Necropsy Evidence of Disseminated Intravascular Coagulation and Hemostatic Variables Before Death in Horses With Colic

Background Disseminated intravascular coagulation (DIC) is frequent in horses with severe gastrointestinal disorders. Postmortem studies have found fibrin microthrombi in tissues of these horses, but studies relating these histopathological findings with antemortem hemostatic data are lacking. Hypothesis Antemortem classification of coagulopathy is related to the presence and severity of fibrin deposits observed postmortem in horses with severe gastrointestinal disorders. Animals Antemortem hemostatic profile data and postmortem tissue samples (kidney, lung, liver) from 48 horses with colic. Methods Tissue samples were stained with phosphotungstic acid hematoxylin and immunohistochemical methods for histological examination. A fibrin score (grades 0–4) was assigned for each technique, tissue and horse, as well as the presence or absence of DIC at postmortem examination. D‐dimer concentration, prothrombin time (PT), activated partial thromboplastin time (aPTT), and antithrombin (AT) activity, as well as the clinicopathological evidence of coagulopathy, were determined from plasma samples collected 0–24 hours before death or euthanasia. Histologic and clinicopathologic data from the same horses were compared retrospectively. Results No association was found between antemortem classification of coagulopathy and postmortem diagnosis of DIC based on tissue fibrin deposition. None of the hemostatic parameters was significantly different between horses with or without postmortem diagnosis of DIC. There was no association between horses with fibrin in tissues or different cut‐offs for D‐dimer concentration and postmortem evidence of DIC. Conclusions and Clinical Importance Abnormalities of the routine clotting profile, including D‐dimer concentration, were not useful in predicting histologic evidence of DIC at necropsy in horses with severe gastrointestinal disorders.

Magnetic Resonance Imaging of Bacterial Meningoencephalitis in a Foal

Magnetic resonance imaging (MRI) in equidae suffering meningoencephalitis (ME) has not been described. The objective of this paper is to describe brain MRI findings in a foal with bacterial ME. A five-month-old, 200 kg bwt Arabian filly was referred with a history of abnormal mental status and locomotion. The filly was recumbent and obtunded, and pupillary light reflexes were sluggish, and oculocephalic movements were normally present. Ophthalmic examination revealed bilateral optic neuritis. Hematology revealed leukocytosis and neutrophilia. Cerebrospinal fluid analysis showed neutrophilic pleocytosis with intracellular bacteria. On brain MRI, there were multifocal cortical areas of mild hyperintensity on T2-weighted images (T2WI) affecting both hemispheres. The lesions had ill-delineated margins, and there was loss of differentiation between gray and white matter. Diffuse hyperintensity was also identified in the left cerebellar cortex on T2WI. Neither mass effect nor cerebral midline shift were identified. On FLAIR images, the lesions were also hyperintense and, in some areas, they seemed to coalescence to form diffuse cortical areas of hyperintensity. The MRI findings described were similar to the MRI features described in cases of humans and small animals with ME. Brain MRI can be a useful diagnostic tool in foals and small-sized equidae with intracranial disease.