Thrombotest (PIVKA) Test Results in 25 Dogs with Acquired and Hereditary Caogulopathies

In the veterinary literature, it has been suggested that a prolongation in the thrombotest (PIVKA test) is a sensitive and diagnostic indicator of anticoagulant rodenticide intoxication. We evaluated prothrombin time (PT), activated partial thromoplastin time (aPTT), and PIVKA indicator in 25 bleeding dogs: 7 with inherited coagulopathies. All dos with acquired coagulopathies had prolonged PIVKA values when compared to the normal controls. Factor VII deficient dogs had a prolonged PIVKA and PT test result, whereas dogs with intrinsic coagulopathies only had an aPTT prolongation. A three-fold increase of the PIVKA or PT values was highly suggestive of an anticoagulant rodenticide poisoning compared to other acquired coagulopathies. Prolonged PIVKA resuls were not specific for anticoagulant rodenticide intoxication in our group of bleeding dogs.     

Proteins invoked by vitamin K absence and clotting times in clinically ill cats

The clinical utility of the Thrombotest, a method for determining the prothrombin time that is uniquely sensitive to the presence of proteins invoked by vitamin K absence (PIVKA), was prospectively evaluated and compared to routine coagulation tests in cats with clinically suspected bleeding tendencies. Abnormal PIVKA clotting values were determined by comparison to results of a concurrently evaluated pooled feline plasma sample and by use of an absolute cutoff value of 25.2 seconds. To be recognized as abnormal, PIVKA clotting values had to be >20% of the pooled feline plasma PIVKA clotting time (the "20% rule") or > or =25.2 seconds (mean + 2 standard deviations of 150 different pooled feline plasma samples). Among the disorders in the population examined were 74 cats with liver disease and 19 cats with severe inflammatory bowel disease. Overall, a prolonged PIVKA clotting time based on the 25.2-second cutoff was found in 39.3% of cats, and based on the 20% rule in 40.7% of cats. An abnormal prothrombin time (PT) developed in 5.8% of cats, an abnormal APTT in 14% of cats, subnormal fibrinogen in 8.8% of cats, and thrombocytopenia in 3.3% of cats. Bleeding tendencies were confirmed in 22 cats, of which abnormal PIVKA clotting times were recognized in 95.5%, abnormal PT in 21%, abnormal activated partial thromboplastin time in 25%, hypofibrinogenemia in 16.7%, and thrombocytopenia in 4.5%. Response to treatment with vitamin K was demonstrated in 21 of 24 cats with an abnormal PIVKA clotting time. In these cats, an abnormal PIVKA clotting time normalized within 3 to 5 days of parenteral vitamin K administration. Cats responding to vitamin K administration had hepatic lipidosis (n = 7), severe inflammatory bowel disease (n = 4), severe inflammatory bowel disease associated with cholangiohepatitis (n = 5), and miscellaneous disorders (n = 5). Using either endpoint, the PIVKA clotting time is more sensitive for the detection of cats with coagulopathies than routinely used coagulation assessments in our hospital. Our findings confirm that cats with hepatic lipidosis, severe cholangiohepatitis, and severe inflammatory bowel disease develop coagulopathies responsive to vitamin K administration.     

Prothrombin, activated partial thromboplastin, and proteins induced by vitamin K absence or antagonists clotting times in 20 hyperthyroid cats before and after methimazole treatment

The effect of daily doses of 5-15 mg of methimazole on the platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), and proteins induced by vitamin K absence or antagonists (PIVKA) clotting time in 20 hyperthyroid cats was determined. No significant (P > .05) difference was found in median platelet count. PT, APTT, or PIVKA clotting time before treatment compared to median values at 2-6 weeks or > or =7-12 weeks of methimazole treatment. No cat had a prolonged APTT at any time. At 2-6 weeks of methimazole treatment, 1 cat each developed thrombocytopenia or prolonged PIVKA clotting time despite initially normal values. Three cats had abnormal coagulation tests (prolonged PT [n = 1] and PIVKA clotting time [n = 3]) before treatment that fluctuated during treatment. Excluding the 3 cats that had abnormal PIVKA clotting time before treatment, prolonged PIVKA clotting time developed in 6% (1/17; 95% confidence interval, 0-28%) cats treated with methimazole for 2-6 weeks. Seemingly. doses of methimazole commonly used to treat hyperthyroidism in cats do not cause alteration in PT and APTT, and only rarely prolong PIVKA clotting time. Nevertheless, abnormal PIVKA clotting time may explain bleeding tendencies unassociated with thrombocytopenia in methimazole-treated hyperthyroid cats.     

Coagulopathic Effects and Therapy of Brodifacoum Toxicosis in Dogs

The clinical signs and laboratory changes of brodifacoum (BDF) intoxicated dogs and their response to vitamin K1 treatment were examined. Brodifacoum, a second-generation anticoagulant rodenticide, was fed to four dogs for 3 consecutive days producing a cumulative dose of 1.1 mg BDF/kg body weight. Clinical observations of the animals were made daily throughout the study. Monitored laboratory parameters included: one-stage prothrombin time (OSPT), activated partial thromboplastin time (APTT), activated coagulation time (ACT), complete blood counts, thrombocyte counts, and serum chemistry values. Response to vitamin K1 therapy was evaluated clinically and by laboratory tests. Serum BDF concentrations were monitored. Inappetence and hemorrhagic tendencies were exhibited by day 5 postrodenticide exposure. One-stage prothrombin time, APTT, and ACT were 25% greater than time zero values at 24, 24, and 72 hours postdosing, respectively. All laboratory parameters returned to normal within 48 hours of initiating vitamin K1 therapy (0.83 mg/kg orally, TID for 5 days). Serum brodifacoum concentrations were highest (1065-1215 ng/mL) during the 3 days after BDF dosing and were detectable (3.0-7.5 ng/mL) until day 24 postexposure. A mean BDF elimination half-life of 6 +/- 4 days was observed.     

Artifactual Prolongation of the Activated Partial Thromboplastin Time Associated With Hemoconcentration in Dogs

An inappropriate blood-to-anticoagulant ratio can cause an artifactual prolongation of the activated partial thromboplastin time (APTT) and prothrombin time (PT). In a drug safety study in dogs, we observed a 4-to 5-second increase in the APTT from baseline coincident with increased hematocrit values (56% to 65%) secondary to drug-induced vomiting and diarrhea. The PT and platelet counts were unchanged, and there was no clinical evidence of bleeding associated with venipuncture. Although we were unable to sample the same dogs to investigate the possible effect of hemoconcentration on the prolonged APTT, the question was addressed by an in vitro study. The hematocrit value for citrated blood samples collected from healthy beagle dogs was increased by the addition of aliquots of red blood cell/plasma mixtures in vitro while maintaining a 9:1 blood-to-anticoagulant ratio. There was a 2-to 4-second prolongation of the APTT associated with hematocrit values of 55% to 61 %, but the PT was not prolonged. Adjustment of the blood-to-anticoagulant ratio corrected the prolongation. This study emphasizes the important relationship of the blood-to-anticoagulant ratio when measuring coagulation tests in hemoconcentrated samples.     

Effect of storage conditions on hemostatic parameters of canine plasma obtained for transfusion

OBJECTIVE: To evaluate the effects of various storage conditions on one-stage prothrombin time (OSPT), activated partial thromboplastin time (APTT), and fibrinogen concentration of canine plasma collected for transfusion. SAMPLE POPULATION: Plasma from 9 dogs. PROCEDURE: Whole blood was collected from dogs by means of jugular venipuncture and centrifuged at 7,300 X g for 20 minutes at 0 C. A plasma extractor was then used to generate plasma. Aliquots of plasma were collected in segments of plastic tubing and in microcentrifuge tubes, and plasma collection bags, tubing segments, and microcentrifuge tubes were immediately frozen at -30 C. Additional tubing segments and microcentrifuge tubes were stored at 2 C. After 1 week of storage, all samples were thawed, and OSPT, APTT, and fibrinogen concentration were measured. Collection bags and microcentrifuge tubes were refrozen at -30 C, and values were measured again 30 days after blood collection. RESULTS: Values for OSPT, APTT, and fibrinogen concentration did not vary significantly with storage time, temperature, or container. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that storage for up to 30 days and at 2 C versus -30 C did not have any significant effect on hemostatic parameters of canine plasma obtained for transfusion.     

Evaluation of the bromosulfophthalein 30-minute retention test for the diagnosis of hepatic disease in dogs

The purpose of this study was to evaluate efficacy of bromosulfophthalein (BSP) retention testing in dogs with and without histopathologically confirmed hepatobiliary disease. Medical records of 150 dogs with hepatobiliary disease having both a BSP test and hepatic biopsy were retrieved. Histopathologic slides of liver tissue were reviewed, and dogs were classified according to 1 of 11 histopathologic categories. Twenty-five clinically normal random-source dogs were used as controls for hepatic biopsy and BSP testing. No dogs suffered adverse effects due to BSP administration. BSP retention was significantly (P < .05) higher in hospitalized (13.9%) than control (3.2%) dogs, but the test could not distinguish between hospitalized dogs with different types of hepatobiliary disease. Sensitivity, specificity, and predictive values of BSP retention as a test for hepatic disease were calculated. Using 5.0% as a cutoff for normal BSP retention resulted in a specificity of 88% and a sensitivity of 76%. Using 6.0% as a cutoff for normal BSP retention resulted in a specificity of 100% and a sensitivity of 70%. Dogs of this study having BSP retention of >6% had at least an 86% chance of having an abnormal liver. We concluded that continued use of BSP retention testing is warranted as a noninvasive diagnostic test for liver disease in dogs.     

Postoperative bleeding in retired racing greyhounds

BACKGROUND: Some retired racing Greyhounds (RRG) that undergo surgery bleed excessively. Hypothesis: Greyhounds that bleed excessively will have one or more preoperative hemostatic abnormalities that can be used to predict the risk and severity of postoperative bleeding. ANIMALS: Eighty-eight RRG undergoing ovariohysterectomy or castration. METHODS: All dogs were evaluated preoperatively with a physical exam, CBC, platelet count, OSPT, APTT, platelet function with PFA-100(a); fibrinogen, d-dimer, plasminogen (Plmg), antiplasmin (AP), antithrombin (AT), and vWF concentration (vWF:Ag); vWF collagen binding assay (vWF:CBA), and Factor XIII assay. Assays were repeated in the dogs that bled, and in an age- and sex-matched control group of RRG. RESULTS: Twenty-six percent of the dogs had bleeding 36-48 hours after surgery. AP (P <.0001) and AT concentration (P= .007) were significantly lower, and vWF:CBA (P= .0284) was higher preoperatively in the dogs with excessive hemorrhage. A lower platelet count (P= .001) and hematocrit (P= .002), shorter OSPT (P= .0002) and higher plasma fibrinogen (P <.0001), and AP (P= .001) concentration were detected at the time of bleeding compared with preoperative values in the dogs that bleed excessively. The same findings were observed postoperatively for the control group, except for the decrease in hematocrit. CONCLUSIONS AND CLINICAL IMPORTANCE: The results indicate that this excessive postoperative bleeding is not attributable to a primary or secondary hemostatic defect, but could result from altered fibrinolysis.     

Comparative diagnostic test characteristics of oscillometric and Doppler ultrasonographic methods in the detection of systolic hypertension in dogs

Comparison of test characteristics allows a clinician to choose the optimal diagnostic test method for an individual patient. This study assessed the comparative test characteristics of noninvasive (NI) blood pressure measurement methods (oscillometric and Doppler) and used this information to develop optimal cutoff values for diagnosis of systolic hypertension in dogs by these NI methods. Simultaneous NI (oscillometric or Doppler methods) and invasive (arterial puncture [AP]) systolic blood pressure (SBP) measurements were obtained prospectively from normal dogs and dogs suspected of having systemic hypertension based on clinical signs. Oscillometric SBP readings were obtained from the distal hind limb (Osc-L, n = 54) or the proximal tail (T. n = 27). Doppler BP measurements were obtained using a forelimb cuff (n = 57). AP-SBP was categorized as hypertensive if > or = 160 mmHg, and sensitivity (Se). specificity (Sp), and likelihood ratios (LR) were calculated for diagnostic cutoff values ranging from 130 to 220 mmHg. Receiver operator characteristic (ROC) curves were analyzed to determine optimal cutoff values for diagnosis of AP-SBP > or = 160 mmHg. Optimal NI SBP cutoff values considered to reflect AP values > or = 160 mmHg were: Osc-L = 160 mmHg (Se: 65%, Sp: 85%. LR = 4.33: 1), Osc-T = 150 mmHg (Se: 84%, Sp: 75%, LR = 3.36: 1), and Doppler = 160 mmHg (Se: 71%,     

Comparison of postprandial and ceruletide serum bile acid stimulation in dogs

BACKGROUND: Postprandial (PP) serum bile acid (SBA) stimulation is an important test for detecting hepatic dysfunction in dogs. However, this test is influenced by numerous variables, and a standardized approach using an injectable cholecystokinin analog (ceruletide) may be advantageous. HYPOTHESIS: Ceruletide SBA stimulation test is more sensitive than PP SBA stimulation in dogs. ANIMALS: Animals with portosystemic shunt (PSS) (n = 11) and dogs with upper respiratory disease (URD) (n = 9) were investigated. Healthy dogs (n = 13) and dogs with other diseases (n = 17) served as controls. METHODS: All dogs underwent SBA stimulation with food and ceruletide. Stimulation blood samples were drawn at 60/120 minutes and 20/30/40 minutes, respectively. Results were compared statistically, and the sensitivity and specificity were determined with receiver-operating characteristic curves. RESULTS: Stimulated SBA were significantly higher in both study groups than in controls. For dogs with PSS, the sensitivity and specificity (>35 micromol/L) were 100% postprandially (120 minutes) and 91 and 100%, respectively, postceruletide (30 minutes). The difference between these values was not statistically significant. For dogs with URD, the sensitivity and specificity (>22 micromol/L) were 44 and 88% postprandially (120 minutes) and 100 and 88% postceruletide (30 minutes). CONCLUSIONS AND CLINICAL IMPORTANCE: Ceruletide SBA stimulation circumvents exogenous and endogenous influences associated with PP SBA stimulation. The results indicate that ceruletide SBA stimulation performs as well as PP SBA stimulation in dogs with PSS and is more sensitive for the detection of hepatic dysfunction in dogs with URD.     

Use of basal serum or plasma cortisol concentrations to rule out a diagnosis of hypoadrenocorticism in dogs: 123 cases (2000-2005)

OBJECTIVE: To determine whether basal serum or plasma cortisol concentration can be used as a screening test to rule out hypoadrenocorticism in dogs. DESIGN: Retrospective case-control study. ANIMALS: 110 dogs with nonadrenal gland illnesses and 13 dogs with hypoadrenocorticism. PROCEDURES: Sensitivity and specificity of basal serum or plasma cortisol concentrations of either 2 microg/dL that are not receiving corticosteroids, mitotane, or ketoconazole are highly unlikely to have hypoadrenocorticism. However, if the basal cortisol concentration is 相似文献   

Evaluation of d,l-ethionine as a mechanism for pancreatic islet regeneration in dogs

OBJECTIVE: To determine whether induction of pancreatic necrosis and islet proliferation by d,l-ethionine has potential for treating dogs with beta-cell insufficiency. DESIGN: Eighteen mixed breed dogs of both sexes were given d,l-ethionine at 100 mg/kg three times weekly for 2 weeks; 6 dogs were euthanased at 2, 14 and 28 d after the last dose. METHODS: Clinical signs during administration and recovery were assessed. Routine biochemical analyses were performed before each ethionine dose and then once weekly. Faecal samples were examined weekly for malassimilated nutrients and blood. Blood coagulation screening tests (OSPT and APTT) were determined on four dogs after ethionine administration. Intravenous glucose tolerance tests were conducted before the first and after the last ethionine dose and then fortnightly. All dogs were necropsied and pancreas, liver, kidney and jejunum were examined microscopically. RESULTS: During ethionine administration all animals displayed vomiting, inappetence, diarrhoea (often with blood), weight loss and depression. Three dogs were euthanased prematurely due to severe illness, but those allowed to recover were eating and brighter 7 d after cessation of ethionine administration. Serum concentrations of TLI, amylase and lipase increased initially, then decreased, during administration but retumed to normal during recovery. Concentrations of ALT, ALP, unconjugated and conjugated bilirubin increased during administration then decreased slowly. Histological examination revealed hepatic lipidosis and necrosis, but no renal or jejunal lesions. In most dogs, faecal examination demonstrated increased undigested starch and muscle, as well as increased digested and undigested fat, during ethionine administration or early during the recovery period, suggesting transient malassimilation. APTT was unchanged but OSPT was prolonged in all dogs. There was no impairment of insulin secretion or glucose intolerance and C-peptide concentrations were unaffected. Immediately after ethionine administration there was delayed insulin degradation and by day 43 there was evidence of increased insulin sensitivity. CONCLUSION: d,l-ethionine administration in dogs appeared not to interfere with insulin secretion, but caused clinical signs and laboratory changes indicative of pancreatic exocrine necrosis, severe hepatobiliary disease and transient malassimilation. Pancreatic and hepatic dysfunction was severe but clinical recovery occurred after ethionine administration ceased. The severe side-effects observed with d,l-ethionine should preclude its potential use for treating diabetes mellitus in dogs.     

Influence of progesterone and pregnancy on canine fibrinogen values

Progesterone alone or in combination with oestrogen was given to male dogs and nonoestrous bitches by intramuscular injection. Progesterone produced a marked increase in plasma fibrinogen values. The fibrinogen response appeared to be independent of oestrogen administration. No alteration in haematocrit values, platelet count, APTT and OSPT results or the activities of coagulation factors VII, VIII and IX was observed following hormone administration. It is suggested that increased plasma progesterone concentrations may be partly responsible for the two- to three-fold increase in fibrinogen which occurs during gestation in the bitch.     

Evaluation of urine sulfated and nonsulfated bile acids as a diagnostic test for liver disease in dogs

OBJECTIVE: To evaluate 3 methods for measuring urine bile acids (UBA) and compare their diagnostic performance with that of the serum bile acids (SBA) test and other routine screening tests in dogs with hepatic disorders. DESIGN: Prospective study. ANIMALS: 15 healthy dogs, 102 dogs with hepatic disorders, and 9 dogs with clinical signs of hepatic disorders that were found to have nonhepatic disorders. PROCEDURES: Blood and urine samples were collected from sick dogs and healthy dogs for serum biochemical analyses, and determination of concentrations of SBA and UBA. Urine samples were obtained from 15 healthy dogs to establish an upper cutoff value for UBA concentrations. The UBA were measured by use of a quantitative-linked enzymatic colorimetric method. Three analytical modifications were evaluated; 1 quantified only urine sulfated bile acids (USBA), 1 only urine nonsulfated bile acids (UNSBA), and 1 quantified both (USBA plus UNSBA). The UBA values were standardized with the urine creatinine concentration. RESULTS: The UNSBA-to-creatinine ratio and USBA plus UNSBA-to-creatinine ratio tests had the best diagnostic performance of the UBA tests; each had a substantially higher specificity, slightly higher positive predictive value, slightly lower negative predictive value, and lower sensitivity than the SBA test. These UBA-to-creatinine values were positively correlated with SBA values. The USBA-to-creatinine ratio had poor sensitivity, indicating a low rate of bile acid sulfation in dogs. CONCLUSIONS AND CLINICAL RELEVANCE: The UBA can be measured in dogs with sufficient repeatability and accuracy for clinical application. The UNSBA-to-creatinine ratio and USBA plus UNSBA-to-creatinine ratio identified dogs with hepatic disorders nearly as well as the SBA test.     

Determination of Normal Values Using an Automated Coagulation Timer for Activated Coagulation Time and its Application in Dogs with Hemophilia

The present study was performed to determine normal values for the Medtronic HemoTec automated activated coagulation time (ACT) analyzer (Medtronic HemoTec Inc, Parker, CO, distributed in Switzerland by Convergenza AG, Vaduz, Liechtenstein), and to evaluate its ability to detect dogs with hemophilia. ACT was measured in 43 healthy dogs presented to the Companion Animal Hospital, University of Bern, Bern, Switzerland, with the Medtronic HemoTec ACT analyzer to determine normal values. The mean +/- 2 standard deviations (SDs) of the values obtained was defined as the normal range. ACT was measured 8-10 times on the same day in 6 dogs to determine repeatability. ACT also was measured in 11 dogs with hemophilia and compared with a conventional visual ACT measurement test and with the activated partial thromboplastin time (APTT). ACT values of the 43 dogs used to determine normal values ranged from 66.5 to 97.0 seconds (mean, 79.3 seconds; SD, 7.35 seconds; median, 78.5 seconds). A range of 64-95 seconds (mean +/- 2 SDs) was defined as the normal range for the tested device. Repeatability was poor (r = 0.256). ACT values measured with the automated device did not correlate with ACT values measured with a conventional visual test or with APTT Sensitivity of the test was 90.9%, specificity was 98.0%, and accuracy was 96.7%. Variability in the test results was large and may lead to incorrect results. The automated measurement device was not superior to the conventional visual method in evaluating dogs with hemophilia.     

Comparison of results of three commercial heartworm antigen test kits in dogs with low heartworm burdens

OBJECTIVE: To compare results of 3 commercial heartworm antigen test kits performed on serum samples from dogs infected with low numbers of adult female heartworms. DESIGN: Blinded laboratory evaluation. Sample Population-Serum samples from dogs (n = 208) proven at necropsy to be infected with 1 to 4 adult female heartworms and from dogs (32) without heartworms. PROCEDURE: Samples were sequentially tested with each test kit, following the manufacturers' instructions, by licensed veterinary technicians in private practice who were not aware of infection status of the dogs. The order of test kit evaluations was randomly chosen. For each test kit, sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were evaluated. RESULTS: All tests yielded some false-negative results, and there were significant differences among tests in regard to ability to detect low heartworm burdens. Sensitivity of the test kits ranged from 78 to 84%. For all test kits, sensitivity increased as number of female heartworms increased. All 3 test kits had high specificity (97%). CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that sensitivity of the 3 commercially available heartworm antigen test kits ranged from 78 to 84% when used to test serum samples from dogs with low heartworm burdens, and that sensitivity varied among test kits. For all 3 test kits, specificity was 97%. All 3 test kits yielded false-positive and false-negative results for some dogs with low heartworm burdens.     

Bile acid concentrations in the diagnosis of hepatobiliary disease in the dog

The clinical usefulness of measuring serum bile acid concentrations as a diagnostic test for hepatobiliary disease, was examined in 150 dogs that were suspected of having hepatic disease. Serum values of total bilirubin (TB), alkaline phosphatase (ALP), alanine transaminase (ALT), and albumin were also measured. Fasting serum bile acid (FSBA) values were determined, using a solid-phase radioimmunoassay for total conjugated bile acids or a direct enzymatic spectrophotometric method. A definitive diagnosis was established by histologic examination of the liver. On the basis of histologic findings, dogs were assigned to groups (1 to 8, respectively) including: extrahepatic bile duct obstruction, cirrhosis, portal systemic vascular anastomosis (PSVA), hepatic necrosis, intrahepatic cholestasis, steroid hepatopathy, neoplasia, and secondary disease. Dogs in group 8 had no morphologic evidence of hepatobiliary disease or had mild hepatic lesions. Test efficacies of FSBA, TB, ALP, ALT, and albumin were expressed using 4 indices: sensitivity, specificity, and positive-predictive and negative-predictive values. The diagnostic efficacy of FSBA was examined alone and in combinations with the other tests. There was wide overlapping of FSBA values among dogs in groups 1 to 7, and there was wide overlapping of ALT and ALP values among dogs in all groups. The specificity of FSBA for the diagnosis of liver disease exceeded 90% at values greater than or equal to 30 mumol/L and reached 100% at greater than or equal to 50 mumol/L. Individual liver tests with the best sensitivity for each group were:FSBA and ALP for extrahepatic bile duct obstruction; FSBA for cirrhosis and PSVA; ALT for hepatic necrosis; and ALP for intrahepatic cholestasis, steroid hepatopathy, and neoplasia. Combinations of tests with the best sensitivity for each group were: FSBA + ALP for extrahepatic bile duct obstruction; FSBA + ALT for cirrhosis and PSVA; FSBA + ALT and TB + ALT for hepatic necrosis; and FSBA + ALP for intrahepatic cholestasis, steroid hepatopathy, and neoplasia. Individual tests had the best sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of d,l-ethionine as a mechanism for pancreatic islet regeneration in dogs

Objective To determine whether induction of pancreatic necrosis and islet proliferation by d,l‐ethionine has potential for treating dogs with b ‐cell insufficiency. Design Eighteen mixed breed dogs of both sexes were given d,l‐ethionine at 100 mg/kg three times weekly for 2 weeks; 6 dogs were euthanased at 2, 14 and 28 d after the last dose. Methods Clinical signs during administration and recovery were assessed. Routine biochemical analyses were performed before each ethionine dose and then once weekly. Faecal samples were examined weekly for malassimilated nutrients and blood. Blood coagulation screening tests (OSPT and APTT) were determined on four dogs after ethionine administration. Intravenous glucose tolerance tests were conducted before the first and after the last ethionine dose and then fortnightly. All dogs were necropsied and pancreas, liver, kidney and jejunum were examined microscopically. Results During ethionine administration all animals displayed vomiting, inappetence, diarrhoea (often with blood), weight loss and depression. Three dogs were euthanased prematurely due to severe illness, but those allowed to recover were eating and brighter 7 d after cessation of ethio‐nine administration. Serum concentrations of TLI, amylase and lipase increased initially, then decreased, during administration but returned to normal during recovery. Concentrations of ALT, ALP, unconjugated and conjugated bilirubin increased during administration then decreased slowly. Histological examination revealed hepatic lipidosis and necrosis, but no renal or jejunal lesions. In most dogs, faecal examination demonstrated increased undigested starch and muscle, as well as increased digested and undigested fat, during ethio‐nine administration or early during the recovery period, suggesting transient malassimilation. APTT was unchanged but OSPT was prolonged in all dogs. There was no impairment of insulin secretion or glucose intolerance and C‐peptide concentrations were unaffected. Immediately after ethionine administration there was delayed insulin degradation and by day 43 there was evidence of increased insulin sensitivity. Conclusion d,l‐ethionine administration in dogs appeared not to interfere with insulin secretion, but caused clinical signs and laboratory changes indicative of pancreatic exocrine necrosis, severe hepatobiliary disease and transient malas‐similation. Pancreatic and hepatic dysfunction was severe but clinical recovery occurred after ethionine administration ceased. The severe side‐effects observed with d,l‐ethionine should preclude its potential use for treating diabetes mellitus in dogs.     

Hemostatic Disorders in Feline Immunodeficiency Virus-Seropositive Cats

The hemostatic function of 40 feline immunodeficiency virus (FlV) seropositive and 8 FIV and feline leukemia virus (FeLV) seropositive cats was evaluated and compared with reference values from 30 clinically healthy cats. The FIVpositive cats were divided into 3 groups: group I included asymptomatic carriers; group II comprised sick FIV-infected cats with illnesses not likely to influence the hemostatic system; and group III included FIV-positive cats with diseases potentially associated with coagulopathies. Platelet counts in FIV/FeLV-infected cats were significantly lower than in healthy cats (P < .003), whereas the differences in the 3 groups of FIV-positive cats were variable (group I, P= .009; II, P= .05; III, P= .09). Thrombocytopenia (< 145,000 platelets/μL) was present in 4 FIV-positive and 3 FIV/FeLV-positive cats. Platelet aggregation induced by collagen (0.5 and 0.25 μg/mL), adenosine diphosphate (ADP) (1 and 0.6 μmol/L), and thrombin (0.4 and 0.25 IU/mL) was not significantly different from that of healthy cats. The plasma coagulation system was evaluated by measuring one-stage prothrombin time (OSPT), activated partial thromboplastin time (APTT), thrombin time, fibrinogen concentration, coagulation factor assays, fibrinogen and fibrin degradation products (FDP), and plasma exchange test. The OSPT was similar in FlV-seropositive cats and in the healthy control group. Cats with FIV infection, however, had markedly shorter clotting times than healthy cats when using a modified test system (P < .05). In all groups of FIV-infected cats and in those with FIV/FeLV infection, APTT measured with 2 different commercially available tests, and a modified plasma assay was markedly prolonged compared with healthy cats (APTT1 and 2:3 modification: P < .01; APTT2: P < .05 except group III). In 22 of 40 cats with FIV and in 5 of 8 cats with FIV/FeLV infection, plasma samples were beyond the reference range. The thrombin time was also significantly prolonged in cats with FIV and FIV/FeLV infection (P < .01); values in 17 of 40 FIV-positive cats were above reference range. The mean fibrinogen concentration of cats with FIV and FIV/FeLV infection was higher than in the healthy control group (P < .001). Factor VIII activity of 4 cats with FIV infection was 1.5 times higher than that of healthy cats. Factor XII activity of 3 cats from a group of 20 cats with prolonged APTT was between 20% and 35%. Factor IX and XI activities ranged between 70% and 120%. The markedly prolonged APTT in 2 FIV-positive cats could be shortened considerably in a plasma exchange test using 20% feline pooled plasma. The alterations in the coagulogram of FIV-seropositive cats were not related to a clinical stage or concurrent diseases. A definite explanation of the distinct disorder within the intrinsic plasma coagulation system in FIV-infected cats was not found.     

Evaluation of a Portable Meter to Measure Ketonemia and Comparison with Ketonuria for the Diagnosis of Canine Diabetic Ketoacidosis

Background: The diagnosis of canine diabetic ketoacidosis (DKA) usually is based on measurement of urinary acetoacetate (ketonuria). In humans, this test is less sensitive and specific than blood 3-β-hydroxybutyrate (ketonemia) evaluation.
Hypothesis: Ketonemia measurement using a portable meter is more accurate than ketonuria determination with a dipstick to diagnose canine DKA.
Animals: Seventy-two client-owned diabetic dogs with ketonemia, ketonuria, or both.
Methods: Prospective observational study. Based on blood bicarbonate concentration and anion gap, dogs were divided into 2 groups: patients with DKA ( n = 25); patients with diabetic ketosis ( n = 47). Sensitivity, specificity, and positive and negative likelihood ratio (LR) at different cut-off points were determined for both ketonemia and ketonuria. Receiver operating characteristic (ROC) analysis was used to assess the accuracy of each diagnostic test to diagnose DKA.
Results: With regard to ketonemia, cut-off values of 2.3 and 4.3 mmol/L revealed 100% sensitivity and 100% specificity, respectively, whereas cut-off values of 2.8 and 3.5 mmol/L showed a −LR of 0.05 and a + LR of 13.16, respectively. With regard to ketonuria, a cut-off value of 1+ revealed 92% sensitivity, 40% specificity, and −LR of 0.20, whereas a cut-off value of 3+ revealed 44% sensitivity, 94% specificity, and +LR of 6.89. The areas under the ROC curves for the ketonemia and ketonuria tests were significantly different (0.97 and 0.81, respectively, P = .003).
Conclusions and Clinical Importance: Measurement of ketonemia is accurate and more effective than measurement of ketonuria to diagnose canine DKA.