Diagnostic and predictive ability of hyperbilirubinemia severity in cats: A multicenter retrospective study.

BACKGROUND: Total serum bilirubin concentration (TBIL) can provide useful information on several pathophysiological conditions in cats. Nevertheless, whether the variable severity classification of hyperbilirubinemia can reliably indicate certain disease processes or predict a biliary obstruction (BO) has not been investigated. HYPOTHESIS/OBJECTIVE: Determine if hyperbilirubinemia of variable severity can assist clinicians to identify BO, which often is considered a surgical emergency. ANIMALS: Two-hundred sixteen client-owned cats. METHODS: Data were retrospectively collected from all cats (January 2015-August 2022) with an increased TBIL (>0.58 mg/dL [>10 µmol/L]) presented to 3 referral centers in the United Kingdom (UK). Presenting clinical features and diagnostic outcomes were collected. The predictive ability of TBIL to indicate BO was evaluated by multivariable binary logistic regression modeling and receiver operating characteristic (ROC) curves. RESULTS: Median TBIL was 1.73 mg/dL (range, 0.59-26.15; 29.5 µmol/L; range, 10.1-447.1) with severity classification of hyperbilirubinemia categorized as mild (>0.58-2.92 mg/dL; >10-50 µmol/L; 68.1%), moderate (>2.92-5.85 mg/dL; >50-100 µmol/L; 17.6%), severe (>5.85-11.70 mg/dL; >100-200 µmol/L; 9.7%) and very severe (>11.70 mg/dL; >200 µmol/L; 4.6%). Biliary obstruction was present in 17 (7.9%) cats, all of which received recommendation for emergency surgery. Median TBIL in cats with BO (9.69 mg/dL; 165.7 µmol/L) differed significantly from those without obstruction (1.51 mg/dL; 25.8 µmol/L; P < .01). The optimal TBIL cut-off to discriminate between cats with and without BO was ≥3.86 mg/dL (≥66 µmol/L) with a sensitivity of 94.1% and specificity of 82.4%. Using multivariable logistic regression, as age increased, the odds of BO increased significantly (odds ratio, 1.20; 95% confidence interval, 1.01-1.42; P = .04). CONCLUSIONS AND CLINICAL IMPORTANCE: As part of a thorough clinical assessment, the severity classification of hyperbilirubinemia has the potential to predict the likelihood of a BO and to discriminate between cats that may or may not require surgery for BO at a suggested cut-off of ≥3.86 mg/dL (≥66 µmol/L). Alongside TBIL, age is also useful when assessing for the likelihood of BO in a cat presented with hyperbilirubinemia.

Doxorubicin and zoledronate treatment in a dog with hemophagocytic histiocytic sarcoma.

A 6-year-old castrated male greyhound dog was referred for hemophagocytic histiocytic sarcoma (HHS) diagnosed following splenectomy. Severe thrombocytopenia, mild hypoalbuminemia, mild hypocholesterolemia, and mild hyperbilirubinemia were present. Abdominal ultrasound findings were concerning for hepatic metastasis. Doxorubicin and zoledronate combination therapy was initiated. The dog improved clinically and its thrombocytopenia, hypoalbuminemia, and hyperbilirubinemia resolved. The dog appeared well for 147 d before tumor progression was noted. The dog was treated with lomustine as a final measure, with no response. The dog survived for 6 mo with chemotherapy. To the authors' knowledge, this is the first report of clinical benefit of chemotherapy for HHS. Key clinical message: Doxorubicin should be considered for treating canine HHS since this variant of the disease is historically refractory to lomustine. Further research regarding efficacy of doxorubicin and zoledronate should be pursued.

Traitement à la doxorubicine et au zolédronate chez un chien atteint de sarcome histiocytaire hémophagocytaire. Un lévrier mâle castré de 6 ans a été vu pour un sarcome histiocytaire hémophagocytaire (HHS) diagnostiqué à la suite d'une splénectomie. Une thrombopénie sévère, une hypoalbuminémie légère, une hypocholestérolémie légère et une hyperbilirubinémie légère étaient présentes. Les résultats de l'échographie abdominale étaient préoccupants quant aux métastases hépatiques. Un traitement associant doxorubicine et zolédronate a été instauré. Le chien s'est amélioré cliniquement et sa thrombocytopénie, son hypoalbuminémie et son hyperbilirubinémie ont disparu. Le chien semblait en bonne santé pendant 147 jours avant de constater une progression tumorale. Le chien a été traité avec de la lomustine comme mesure finale, sans réponse. Le chien a survécu 6 mois grâce à la chimiothérapie. À la connaissance des auteurs, il s'agit du premier rapport faisant état d'un bénéfice clinique de la chimiothérapie pour le HHS.Message clinique clé :La doxorubicine doit être envisagée pour traiter le HHS canin puisque cette variante de la maladie est historiquement réfractaire à la lomustine. Des recherches plus approfondies concernant l'efficacité de la doxorubicine et du zolédronate devraient être poursuivies.(Traduit par Dr Serge Messier).

Serum biochemical changes in cats with naturally acquired feline cytauxzoonosis.

OBJECTIVE: The geographical distribution of feline cytauxzoonosis is expanding in the US. Clinical signs of feline cytauxzoonosis, including lethargy, anorexia, and icterus, are similar to hepatic lipidosis and cholangiohepatitis. Hematologic and serum biochemical abnormality patterns may assist practitioners in prioritizing feline cytauxzoonosis as a differential diagnosis over hepatic lipidosis and cholangiohepatitis. SAMPLE: Hematology and serum biochemical profiles of cats with naturally acquired feline cytauxzoonosis, hepatic lipidosis, or cholangiohepatitis. PROCEDURES: Retrospective search and analysis of the Kansas State Veterinary Diagnostic Laboratory or Kansas State University Veterinary Health Center records between January 2007 and June 2018 for cats with cytauxzoonosis, hepatic lipidosis, or cholangiohepatitis. RESULTS: Patients with acute feline cytauxzoonosis presented with frequent nonregenerative anemia (20/28 [71%]), leukopenia (23/28 [82%]), thrombocytopenia (23/23 [100%]), hyperbilirubinemia (27/28 [97%]), hypoalbuminemia (26/28 [93%]), reduced (18/28 [64%]) or low normal (10/28 [36%]) serum ALP activity, and hyponatremia (23/28 [82%]). Reduced ALP activity was unique to cats with feline cytauxzoonosis relative to hepatic lipidosis and cholangiohepatitis. No correlation between the severity of anemia and the magnitude of hyperbilirubinemia was identified in feline cytauxzoonosis patients. CLINICAL RELEVANCE: The combination of nonregenerative anemia, leukopenia, thrombocytopenia, hyperbilirubinemia, and reduced serum ALP activity in icteric cats may increase the clinical suspicion, but is not pathognomonic, for acute feline cytauxzoonosis. Hematologic and serum biochemical abnormalities of naturally acquired feline cytauxzoonosis are like those reported with feline bacterial sepsis. Blood smear evaluation for intraerythrocytic Cytauxzoon felis piroplasms, tissue aspirates for schizont-laden macrophages, and/or molecular testing are required to diagnose feline cytauxzoonosis.

Effect of clinical signs, endocrinopathies, timing of surgery, hyperlipidemia, and hyperbilirubinemia on outcome in dogs with gallbladder mucocele.

Gallbladder mucocele (GBM) is a common extra-hepatic biliary syndrome in dogs with death rates ranging from 7 to 45%. Therefore, the aim of this study was to identify the association of survival with variables that could be utilized to improve clinical decisions. A total of 1194 dogs with a gross and histopathological diagnosis of GBM were included from 41 veterinary referral hospitals in this retrospective study. Dogs with GBM that demonstrated abnormal clinical signs had significantly greater odds of death than subclinical dogs in a univariable analysis (OR, 4.2; 95% CI, 2.14-8.23; P<0.001). The multivariable model indicated that categorical variables including owner recognition of jaundice (OR, 2.12; 95% CI, 1.19-3.77; P=0.011), concurrent hyperadrenocorticism (OR 1.94; 95% CI, 1.08-3.47; P=0.026), and Pomeranian breed (OR, 2.46; 95% CI 1.10-5.50; P=0.029) were associated with increased odds of death, and vomiting was associated with decreased odds of death (OR, 0.48; 95% CI, 0.30-0.72; P=0.001). Continuous variables in the multivariable model, total serum/plasma bilirubin concentration (OR, 1.03; 95% CI, 1.01-1.04; P<0.001) and age (OR, 1.17; 95% CI, 1.08-1.26; P<0.001), were associated with increased odds of death. The clinical utility of total serum/plasma bilirubin concentration as a biomarker to predict death was poor with a sensitivity of 0.61 (95% CI, 0.54-0.69) and a specificity of 0.63 (95% CI, 0.59-0.66). This study identified several prognostic variables in dogs with GBM including total serum/plasma bilirubin concentration, age, clinical signs, concurrent hyperadrenocorticism, and the Pomeranian breed. The presence of hypothyroidism or diabetes mellitus did not impact outcome in this study.

Pseudo-hypoproteinemia in a hyperbilirubinemic dog with immune-mediated hemolytic anemia.

A 10-year-old spayed female Miniature Poodle was presented to the University of Georgia veterinary teaching hospital for evaluation of lethargy, vomiting and anorexia of 4 days' duration. Physical examination, history and a minimum database led to a diagnosis of immune-mediated hemolytic anemia accompanied by marked hyperbilirubinemia. Refractometric protein determination was within the reference interval, whereas the biuret method indicated hypoproteinemia. This discrepancy was attributed to interference of bilirubin and biliverdin with the spectrophotometric read-out of the biuret total protein assay. The albumin concentration, determined by bromcresol green, and refractometric total protein were less affected by this interference.

Refractometric total protein concentrations in icteric serum from dogs.

OBJECTIVE: To determine whether high serum bilirubin concentrations interfere with the measurement of serum total protein concentration by refractometry and to assess potential biases among refractometer measurements. DESIGN: Evaluation study. SAMPLE: Sera from 2 healthy Greyhounds. PROCEDURES: Bilirubin was dissolved in 0.1M NaOH, and the resulting solution was mixed with sera from 2 dogs from which food had been withheld to achieve various bilirubin concentrations up to 40 mg/dL. Refractometric total protein concentrations were estimated with 3 clinical refractometers. A biochemical analyzer was used to measure biuret assay-based total protein and bilirubin concentrations with spectrophotometric assays. RESULTS: No interference with refractometric measurement of total protein concentrations was detected with bilirubin concentrations up to 41.5 mg/dL. Biases in refractometric total protein concentrations were detected and were related to the conversion of refractive index values to total protein concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: Hyperbilirubinemia did not interfere with the refractometric estimation of serum total protein concentration. The agreement among total protein concentrations estimated by 3 refractometers was dependent on the method of conversion of refractive index to total protein concentration and was independent of hyperbilirubinemia.

MRI findings in a dog with kernicterus.

A severe increase in total bilirubin coincided with a decline in neurologic status to comatose in a 9 yr old spayed female mixed-breed dog being treated for immune-mediated hemolytic anemia. MRI of the brain was performed to investigate potential causes for the neurologic signs. MRI revealed bilaterally symmetrical hyperintensities within the caudate nuclei, globus pallidus, thalamus, deep cerebellar nuclei, and cortical gray matter on T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequences, which coincided with areas of bilirubin deposition and neuronal necrosis (kernicterus) identified on necropsy examination. This is the second case report of an adult dog exhibiting kernicterus, and the first report to document MRI findings associated with that condition. Kernicterus is an uncommonly reported complication of hyperbilirubinemia in dogs, but is potentially underreported due to difficulties in recognizing subtle lesions and distinguishing kernicterus from other potential causes of neurologic abnormalities with readily available antemortem tests. MRI may be helpful in supporting the diagnosis of kernicterus.

Analytical performance of commercially-available assays for feline insulin-like growth factor 1 (IGF-1), adiponectin and ghrelin measurements.

The objective of this study was to evaluate three commercially-available human assays for the determination of adiponectin, ghrelin and insulin-like growth factor 1 (IGF-1) concentrations in feline serum samples. Intra- and interassay coefficients of variation were lower than 20%, 15% and 6% for adiponectin, ghrelin and IGF-1 assays, respectively. Dilutions of feline serum pools resulted in linear regression equations in all kits. Mean recovery of adiponectin, ghrelin and IGF-1 assays were 107%, 102% and 105%, respectively. Significant differences were detected in adiponectin and ghrelin concentrations between lean and obese cats (P <0.05 in both cases), but there was no difference in IGF-1 concentrations (P = 0.12).

Effects of haemolysis, lipaemia and bilirubinaemia in canine C-reactive protein and haptoglobin determination by time-resolved fluorometry: short communication.

C-reactive protein (CRP) and haptoglobin (Hp) are well-known acute phase proteins in the dog. Currently, a commercial ELISA and a colorimetric assay are the methods of choice for measuring CRP and Hp, respectively; however, these assays showed interference when using haemolysed, lipaemic or hyperbilirubinaemic samples. Recently, time-resolved immunofluorometric assays (TR-IFMAs) have been developed for measuring canine CRP and Hp. The aim of the present study was to evaluate the effect of increasing concentrations of haemoglobin, lipids and bilirubin in CRP and Hp serum measurements using these new fluoroimmunoassays. Haemolysis was produced by freezing blood cells at -20 degrees C. The haemolysate was added to pooled sera at final concentrations of 0, 2.5, 5, 10, 20 and 40 g/L. A commercial emulsion of triglycerides was added to homologous pooled sera at 0, 0.35, 0.7, 1.4, 2.8, 5.6 and 11.2 mmol/L. Bilirubin, initially dissolved in dimethyl sulphoxide, was added to pooled sera at 0, 64.2, 128.4, 256.8, 513.7 and 1027.4 micromol/L. Addition of fresh haemolysate, triglycerides or bilirubin to serum samples did not affect either CRP or Hp concentrations (P > or = 0.18), so the TR-IFMAs could be an alternative to the traditional tests for measuring canine CRP and Hp in those laboratories where immunofluorometric assays are available.

Zinc intoxication in dogs: 19 cases (1991-2003).

OBJECTIVE: To determine physical examination findings, clinicopathologic changes, and prognosis in dogs with zinc toxicosis. DESIGN: Retrospective case series. ANIMALS: 19 dogs with zinc toxicosis. PROCEDURES: Medical records from 1991 through 2003 were searched for animals with a diagnosis of zinc toxicosis. Information concerning signalment, body weight, historical findings, initial owner complaints, physical examination findings, clinicopathologic findings, blood zinc concentrations, source of zinc, treatments given, duration of hospital stay, and outcome was collected. RESULTS: Records of 19 dogs with zinc toxicosis were reviewed. The most common historical findings were vomiting (n = 14) and pigmenturia (12). The most common clinicopathologic findings were anemia (n = 19) and hyperbilirubinemia (12). Median age was 1.3 years, and median weight was 5.6 kg (12.3 lb). The prognosis was favorable, with 17 dogs surviving after a median hospital stay of 2 days. CONCLUSIONS AND CLINICAL RELEVANCE: Hemolytic anemia as a result of zinc toxicosis appeared to affect young small-breed dogs more frequently than older large-breed dogs. The prognosis with treatment is good, and most affected dogs had a short hospital stay.

Treatment and long-term follow-up of extrahepatic biliary obstruction with bilirubin cholelithiasis in a Somali cat with pyruvate kinase deficiency.

A 2-year-old female neutered Somali cat was presented with vomiting and acute onset jaundice 1 year after diagnosis of pyruvate kinase (PK) deficiency. Diagnostic investigations revealed a moderate regenerative haemolytic anaemia, severe hyperbilirubinaemia and elevated liver enzymes. Ultrasonography revealed marked distension of the gall bladder and common bile duct (CBD), consistent with extrahepatic biliary obstruction (EHBO). At cholecystotomy, the gall bladder contained purulent material, and two obstructive choleliths were removed from the CBD by choledochotomy. The cat recovered from surgery uneventfully, and serum liver enzymes and bilirubin normalised within 10 days. Postoperative treatment consisted of cephalexin, metronidazole and ursodeoxycholic acid (UDCA). Bacterial culture of the gall bladder contents yielded a pure growth of an Actinomyces species. Cholelith analysis revealed that they consisted of 100% bilirubin. Antibiotic treatment was stopped 4 weeks after surgery but UDCA was continued indefinitely. The cat remains clinically well with no recurrence of cholelithiasis 20 months after initial presentation. This is the first report of successful treatment and long-term follow-up of a cat with EHBO due to bilirubin cholelithiasis in association with PK deficiency-induced chronic haemolysis.

Cholecystoenterostomy for treatment of extrahepatic biliary tract obstruction in cats: 22 cases (1994-2003).

OBJECTIVE: To identify factors associated with outcome in cats with extrahepatic biliary tract obstruction (EHBTO) that undergo biliary diversion surgery. DESIGN: Retrospective case series. ANIMALS: 22 cats. PROCEDURES: Medical records of cats with surgically confirmed EHBTO that underwent cholecystoenterostomy were reviewed. RESULTS: Clinical signs and physical examination findings included vomiting, anorexia, icterus, lethargy, weakness, and weight loss. Common clinicopathologic abnormalities included high serum hepatic enzyme activities and serum bilirubin concentration. Abdominal ultrasonography was performed in 21 cats, and all 21 had findings consistent with EHBTO. Eleven of 15 cats in which blood pressure was monitored had intraoperative hypotension. Eighteen cats had anemia following surgery, and 14 cats had persistent hypotension. Extrahepatic biliary tract obstruction was a result of neoplasia in 9 cats and chronic inflammatory disease in 13. Fourteen cats survived long enough to be discharged from the hospital, but only 6 survived > 6 months after surgery, all of which had chronic inflammatory disease. Median survival time for cats with neoplasia (14 days) was significantly shorter than that for cats with inflammatory disease (255 days). No other variable was associated with outcome. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that cats with EHBTO secondary to neoplasia have a poorer prognosis than cats with EHBTO secondary to chronic inflammatory disease. However, the overall prognosis for cats with EHBTO undergoing cholecystoenterostomy must be considered guarded to poor, and the incidence of perioperative complications is high.

Effects of hemolysis, lipemia, hyperbilirrubinemia, and anticoagulants in canine C-reactive protein, serum amyloid A, and ceruloplasmin assays.

The objective of the present study was to determine the effects that hemolysis, lipemia, bilirubinemia, and anticoagulants might have on the most commonly used assays for C-reactive protein and serum amyloid A, and determination of ceruloplasmin values in dogs. Solutions of hemoglobin, lipid, and bilirubin were added to serum aliquots. Additionally, serum and plasma samples with different anticoagulants (heparin, EDTA, and citrate) were obtained from healthy dogs. Hemolysis, lipemia, and hyperbilirubinemia interfered significantly with the C-reactive protein and ceruloplasmin results, but not with those for the serum amyloid A assay. The use of anticoagulants produced significant changes in the results for the assays tested. However, the magnitude of the differences caused by the interfering substances does not appear to have an important impact on the clinical interpretation of the tests.

Single hepatic venous injection of liver-specific naked plasmid vector expressing human UGT1A1 leads to long-term correction of hyperbilirubinemia and prevention of chronic bilirubin toxicity in Gunn rats.

Previously, we have demonstrated that hepatic venous injection of pcDNA3hUGT1A1 expressing human bilirubin glucuronosyl transferase 1A1 (hUGT1A1) under the control of the cytomegalovirus promoter results in excretion of bilirubin glucuronides in bile and significant decrease in serum bilirubin for at least 2 weeks in the Gunn rat, an animal model of Crigler-Najjar syndrome type I. In this study we compared repeat delivery of pcDNA3hUGT1A1 with single injection of pBShUGT1A1 expressing hUGT1A1 under liver-specific regulatory control, for treatment of hyperbilirubinemia in the Gunn rat. Although repeat injections of pcDNA3hUGT1A1 consistently reduced serum bilirubin levels, the effect did not exceed 2 weeks; hUGT1A1 was detectable in livers only for 2 weeks, despite the presence of vector and transcript for at least 1 month. In contrast, injection of pBShUGT1A1 resulted in persistence of vector, transcript, and recombinant protein and sustained correction of hyperbilirubinemia for at least 8 months; furthermore, renal tubular damage, the principal manifestation of chronic bilirubin toxicity in the Gunn rat, was prevented. Sera from animals treated with pBShUGT1A1 consistently contained anti-hUGT1A1 antibodies, but a significant increase in the number of hepatic CD4(+) and CD8(+) cells was seen only in the pcDNA3hUGT1A1 group; thus liver-specific expression of hUGT1A1 may attenuate immune response. Our results provide further evidence of the feasibility of long-term correction of hepatic enzyme deficiencies with plasmid vectors optimized for expression in the liver.

Cortisol and free thyroxine determination by time-resolved fluorometry in canine serum.

Validation for canine serum of 2 commercially available time-resolved fluoroimmunoassays (TR-FIAs) designed for analysis of cortisol and free thyroxine (fT4) in human serum was carried out. Included was the study of interference by hemolysis, lipemia, and bilirubinemia. With the dissociation enhancement lanthanide fluoroimmunoassay kits, the intra-assay coefficient of variation (CV) ranged from 6.4% to 8.7% for cortisol and from 5.3% to 9.8% for fT4; the interassay CVs ranged from 5.8% to 10.8% and from 3.9% to 14.1%, respectively. Accuracy was evaluated by comparing cortisol and fT4 results obtained with TR-FIA and those obtained with a validated enzyme-linked immunosorbent assay (ELISA) and an equilibrium dialysis (ED) assay, respectively. The regression equations obtained were y = 0.57x + 1.18 (r2 = 0.90) for cortisol and y = 0.87x + 0.82 (r2 = 0.93) for fT4. The limits of detection for cortisol and fT4 were 4.84 nmol/L and 2.68 pmol/L, respectively. The results of adrenocorticotropin-stimulation and dexamethasone-suppression tests were similar to those published previously; likewise, serial dilution of a canine serum sample with a high cortisol content demonstrated that the TR-FIA was immunologically specific. Serial dilution of a serum sample with a high fT4 concentration showed a methodologic bias, a dependence on serum binding capacity, which indicates that the results obtained with this method should be interpreted with caution. Finally, hemolysis and lipemia significantly interfered with cortisol and fT4 measurements, whereas bilirubinemia did not affect the results.

Pathogenesis and outcome of extrahepatic biliary obstruction in cats.

Extrahepatic biliary obstruction (EHBO) was confirmed at surgery or necropsy in 22 cats. Biliary or pancreatic adenocarcinoma was diagnosed by histopathology in six cats and one cat had an undiagnosed mass in the common bile duct. The remaining 15 cats had at least one of a complex of inflammatory diseases including pancreatitis, cholangiohepatitis, cholelithiasis and cholecystitis. The most common clinical signs were jaundice, anorexia, lethargy, weight loss and vomiting. Hyperbilirubinaemia was present in all cases. Distension of the common bile duct and gall bladder was the most commonly observed finding on abdominal ultrasound. Nineteen cats underwent exploratory laparotomy for biliary decompression and diversion. Mortality in cats with underlying neoplasia was 100 per cent and, in those with non-neoplastic lesions, was 40 per cent. Long-term complications, in those that survived, included recurrence of cholangiohepatitis, chronic weight loss and recurrence of obstruction. Based on these findings, the prognosis for EHBO in cats must be considered guarded.

Evaluation of fructosamine in dogs and cats with hypo- or hyperproteinaemia, azotaemia, hyperlipidaemia and hyperbilirubinaemia.

The influence of various pathological conditions on fructosamine levels in normoglycaemic dogs and cats was investigated. The most frequent and most pronounced deviations were found in animals with hypoproteinaemia, in which fructosamine was significantly lower than in the controls. In 66 per cent of the dogs and 67 per cent of the cats with hypoproteinaemia the levels were below the reference range. In the dogs the concentration of fructosamine was correlated with the level of albumin, but in the cats it was correlated with the level of total protein. Dogs with hyperlipidaemia and azotaemia also had significantly lower levels of fructosamine; 38 per cent of those with hyperlipidaemia and 47 per cent of those with azotaemia had fructosamine levels outside the reference range. No significant changes in fructosamine were detected in dogs or cats with hyperproteinaemia or hyperbilirubinaemia, or in cats with hyperlipidaemia or azotaemia.

Risk factors for enterolithiasis among horses in Texas.

OBJECTIVE: To identify risk factors for enterolithiasis in horses. DESIGN: Matched case-control study. ANIMALS: 26 horses with enteroliths, 104 horses with other causes of colic that underwent surgery (52 horses, surgical control group) or were treated medically (52 horses, nonsurgical control group). PROCEDURE: Medical records were reviewed for horses with enteroliths and control horses. Information collected included signalment, anamnesis, and findings on physical examination and clinicopathologic testing at admission. Horses with enteroliths and control horses were compared by means of conditional logistic regression to identify factors associated with enterolithiasis. RESULTS: Horses that were fed alfalfa hay, spent < or = 50% of time outdoors, or were Arabian or miniature breeds had an increased risk of developing enteroliths. Horses with enteroliths were more likely to have been hyperbilirubinemic and to have had clinical signs > 12 hours prior to admission. CONCLUSIONS AND CLINICAL RELEVANCE: Breed and diet appear to influence the risk of enterolithiasis; other management factors also may influence development of enteroliths. Duration of clinical signs may be longer and signs may be less severe among horses with enteroliths, compared with horses with other causes of colic.