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1.
Anticoagulant effects of low-molecular-weight heparins in healthy cats   总被引：4，自引：0，他引：4  
BACKGROUND: Low-molecular-weight heparin (LMWH) has potential benefit in cats at risk for thromboembolic disease. However, LMWH pharmacokinetics has not been characterized in the cat. Drug effect with LMWH may be evaluated with analysis of factor Xa inhibition (anti-Xa) or thromboelastography (TEG). HYPOTHESIS: Administration of LMWH at previously recommended dosages and schedules to healthy cats will result in inhibition of factor Xa and hypocoagulable TEG. ANIMALS: In vivo research with heparin was performed in 5 purpose-bred cats. METHODS: In a prospective study with randomized crossover design, heparin or placebo was administered. Treatments were unfractionated heparin (UFH), 250 IU/kg q6h; dalteparin, 100 IU/kg q12h; enoxaparin, 1 mg/kg q12h; or 0.9% saline, 0.25 mL/kg q6h. Each drug was administered for 5 consecutive days followed by a minimum washout of 14 days. Baseline and post-treatment analyses included anti-Xa, TEG, and prothrombin time/activated partial thromboplastin time. RESULTS: Mean anti-Xa activity 4 hours after enoxaparin (0.48 U/mL) approached the human therapeutic target (0.5-1.0 U/mL); however, mean trough anti-Xa activity was below detection limits. Mean anti-Xa activity 4 hours after dalteparin was lower, and only 1 cat attained therapeutic target at a single time point. Cats receiving UFH attained target anti-Xa activity and changes in TEG at trough and 4 hours. CONCLUSIONS: Cats have rapid absorption and elimination kinetics with LMWH therapy. On the basis of pharmacokinetic modeling, cats will require higher dosages and more frequent administration of LMWH to achieve human therapeutic anti-factor Xa activity of 0.5-1 U/mL. Peak anti-Xa activity is predicted at 2 hours after administration of LMWH.  相似文献   

2.
Background: Low‐molecular‐weight heparin (LMWH) is being used increasingly in veterinary medicine for both treatment and prophylaxis of thromboembolic disease, but no predictable patient‐side method exists to monitor its effect. Objectives: The aim of this study was to evaluate thromboelastography (TEG) and prothombinase‐induced clotting time (PiCT) assays for detecting hemostatic alterations following in vitro heparinization of canine whole blood with dalteparin (Fragmin). Methods: Citrated whole‐blood samples were collected from 7 clinically healthy dogs. Dalteparin was added at concentrations of 0, 0.156, 0.625, 1.25, and 2.5 U/mL of whole blood. TEG was performed using heparinase cups with tissue factor (TF, 1:50,000) and kaolin as activators. Reaction time (R), clotting time (K), angle (α), and maximum amplitude (MA) were recorded. PiCT and anti‐FXa activity were measured in plasma. Results: With TF, increasing concentrations of dalteparin significantly prolonged R and K and significantly decreased α and MA. K, α, and MA ratios were significantly different from baseline at all dalteparin concentrations and R was significantly different from baseline at concentrations of 0.625, 1.25, and 2.5 U/mL. With kaolin, only R was significantly different from baseline at dalteparin concentrations of 0.625 and 2.5 U/mL. PiCT detected dalteparin concentrations ≤ 0.625 U/mL, with a good linear correlation (r2=.96, P<.0001). Conclusion: These results suggest that TF‐activated TEG and PiCT assays should be further evaluated as promising new methods for evaluating the effect of LMWH, using doses in the recommended clinical range and prospective clinical studies.  相似文献   

3.
Low molecular weight heparin (LMWH) is used as an anticoagulant in cats although only limited pharmacokinetic data are available in this species. The aim of the present study was to establish the pharmacokinetics of dalteparin in cats based on anti-FXa heparin activities. Groups of clinically healthy cats (six animals per treatment) received individual LMWH injections at three different doses intravenously (IV) (25, 50, 100 anti-factor Xa international units [IU anti-FXa]/kg) or subcutaneously (SC) (50, 100, 200 IU anti-FXa/kg). Blood samples were collected before and at various times after injection. Anti-FXa activity was measured with a chromogenic substrate test. Following IV injection, maximum plasma heparin activities (C(max)) were 0.67 ± 0.14, 1.44 ± 0.22 and 2.87 ± 0.38 IU anti-FXa/mL, respectively. The calculated mean half-life (t(?)) was between 39 and 57 min and was not significantly dose-dependent (P=0.139). The volume of distribution (35-39 mL/kg) was almost equivalent to the plasma volume. After SC injection, C(max) values of 0.41 ± 0.10, 0.86 ± 0.17 or 1.91 ± 0.16 IU anti-FXa/mL, respectively, were calculated at 91-110 min post-injection. The t(?) values were between 106 and 122 min and were not significantly influenced by dose (P=0.784). The bioavailability after SC injection was approximately 100%. The high bioavailability of the SC administered LMWH dalteparin in cats was consistent with other species and indicated predictable blood levels. However, the comparatively short t(?) may indicate the necessity of multiple daily injections, which should be verified in clinical trials.  相似文献   

4.
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.  相似文献   

5.
Background: A major cause of death in dogs with immune‐mediated hemolytic anemia (IMHA) is thromboembolism. Previous studies suggest unfractionated heparin (UH) is not effective in preventing thromboembolism in IMHA; however, subtherapeutic dosing could explain the seeming lack of efficacy. Hypothesis: Providing therapeutic plasma concentration of UH by individually adjusting doses based on antifactor Xa activity would improve survival in IMHA. Animals: Fifteen dogs with primary IMHA. Methods: Randomized, prospective, controlled clinical trial. Dogs received standardized therapy for IMHA and either constant dose (CD) (150 U/kg SC) (n = 7) or individually adjusted dose (IAD) (n = 8) UH, monitored via an anti‐Xa chromogenic assay, adjusted according to a nomogram. UH was administered every 6 hours until day 7, and every 8 hours thereafter. UH dose was adjusted daily in IAD dogs until day 7, weekly until day 28, then tapered over 1 week. Dogs were monitored for 180 days. Results: At day 180, 7 dogs in the IAD group and 1 in the CD group were alive (P= .01). Median survival time for the IAD group was >180 days, and 68 days for the CD group. Thromboembolic events occurred in 5 dogs in the CD group and 2 dogs in the IAD group. Doses of UH between 150 and 566 U/kg achieved therapeutic anti‐Xa activity (0.35–0.7 U/mL). Conclusions and Clinical Importance: This study suggests that IAD UH therapy using anti‐Xa monitoring reduced case fatality rate in dogs with IMHA when compared with dogs receiving fixed low dose UH therapy.  相似文献   

6.
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.  相似文献   

7.
The low molecular weight heparin (LMWH), dalteparin sodium, was administered subcutaneously (100 IU/kg) to 8 healthy cats twice daily for 13 doses. Anti-activated factor X (anti-Xa) activity was measured prior to administration (time 0), and 4, 6, 8, and 12 h after the 1st dose, 4 h after administration of the 3rd dose, and at 4, 6, 8, and 12 h after the last dose. Four cats developed measurable anti-Xa activity 4 h following a single dose, returning to baseline by 6 h. Anti-Xa activity was not detected at any time point in 4 cats. Prothrombin time (PT), activated partial thromboplastin time (APTT), and antithrombin (AT) concentrations were unaffected by LMWH administration. Dalteparin, at 100 IU/kg SC, did not achieve anti-Xa activity in 4 out of 8 cats and failed to maintain anti-Xa activity beyond 4 h in the other 4 healthy cats.  相似文献   

8.

Background

Accurate diagnostic markers for sepsis in neonatal foals are needed. Plasma C‐reactive protein concentration (p[CRP]) and haptoglobin concentration (p[Hp]) are well‐established biomarkers of infection in humans, but studies are lacking in foals.

Hypotheses

p[CRP]) and p[Hp] are increased in septic foals compared to sick nonseptic and healthy control foals, and are predictive of survival.

Animals

Eighty critically ill foals (40 septic, 40 sick nonseptic) and 39 healthy control foals <1 week of age.

Methods

Multicenter, prospective observational clinical study. Venous blood was collected at admission from septic and sick nonseptic foals and from clinically healthy foals at 24 h of age. A diagnosis of sepsis was made based on positive blood culture or a sepsis score >11, and p[CRP] and p[Hp] were measured by using ELISA tests. Data were analyzed by using the Mann‐Whitney U‐test and forward stepwise multivariable linear regression. P < .05 was considered significant.

Results

Plasma [CRP] was positively associated with age, serum globulin, adrenomedullin, and bilirubin concentrations, aspartate aminotransferase activity, glutamyl‐transferase activity, band neutrophil count, and rectal temperature, and was increased in foals with toxic neutrophils, enterocolitis, colic, rib fractures and septic arthritis. Surprisingly, p[Hp] was lower in septic foals than in sick nonseptic foals. Neither p[CRP] or p[Hp] was predictive of survival in critically ill foals.

Conclusions and Clinical Importance

Plasma [CRP] increases with inflammation in neonatal foals but is not indicative of sepsis. Single time point, admission sampling of p[CRP] and p[Hp] do not appear to be useful biomarkers for sepsis in foals.  相似文献   

9.
OBJECTIVE: To evaluate the effect of plasma transfusion on phagocytosis and oxidative burst activity of peripheral blood neutrophils from healthy and septic equine neonates with sub-optimal passive transfer of maternal immunity. ANIMALS: Nine healthy and seven septic foals with suboptimal passive transfer of maternal immunity (serum IgG < 8 g/L) presented to participating veterinary hospitals for plasma transfusion, and seven healthy foals less than 7 days of age and with circulating IgG concentrations > or = 8 g/L. PROCEDURE: Foals with serum IgG concentrations < 8 g/L were assessed as healthy or septic. Sepsis was recognised by positive bacterial cultures and/or sepsis scores of > or = 11. All foals received between 1 and 3 L of plasma to boost circulating IgG concentrations to > or = 8 g/L. Serum IgG concentrations were determined before and following transfusion by glutaraldehyde coagulation test and confirmed by single radial immunodiffusion assays. Neutrophil phagocytosis and oxidative burst activity were determined before plasma transfusion and at 0 h, 12 h, 24 h, 48 h and 5 d following treatment. Neutrophil function from seven healthy foals less than 7 d of age and with circulating IgG concentrations of > or = 8 g/L was similarly evaluated on a single occasion. RESULTS: Plasma treatment significantly increased circulating IgG concentrations for healthy and septic foals. Oxidative burst activity of neutrophils from septic foals was significantly increased 5 days following treatment, relative to 0 h post treatment. Other differences were not significant but suggested a transient decrease in phagocytosis by neutrophils from healthy foals and increased phagocytosis by neutrophils from septic foals immediately following transfusion. Oxidative burst activity of neutrophils from septic foals tended to be less than that of healthy foals at all sampling times. Serum IgG concentrations were not correlated with neutrophil phagocytosis, but were correlated with oxidative burst activity. CONCLUSIONS: Plasma transfusion did not improve neutrophil function of healthy foals, suggesting that such treatment may be of equivocal benefit for healthy neonates. Conversely, improved neutrophil function was observed following treatment of septic foals, suggesting that plasma transfusion was beneficial for these foals. Oxidative burst activity of neutrophils from septic foals was lower than that of neutrophils from healthy foals and was significantly improved 5 days post treatment, when compared with values obtained immediately following treatment.  相似文献   

10.
The pharmacokinetics of a low molecular weight heparin (LMWH; Fragmin D) was studied in dogs after intravenous and subcutaneous administration, based on antifactor Xa- (anti-fXa-) activity. Each dosage was examined in 5 adult Beagles. After intravenous application of 25, 50 and 100 anti-fXaU./kg body weight (BW) the mean peak plasma heparin activity of 0.52 +/- 0.12 (x +/- s), 1.08 +/- 0.23 and 1.86 +/- 0.17 anti-fXaU./ml, respectively, was measured. After subcutaneous application of 50, 100 and 200 anti-fXaU./kg BW maximum heparin activity in the plasma was determined after 144-216 minutes (mean values) of 0.28 +/- 0.01, 0.52 +/- 0.06 or 1.09 +/- 0.20 anti-fXaU./ml. Intravenous application of LMWH has a short plasma terminal half-life (t50) between 49 and 76 minutes which depended on the dosage. After administration of 50 anti-fXaU./kg BW (74 minutes) and 100 anti-fXaU./kg BW (76 minutes) no essential difference was shown. A distinctly longer t50 was found after subcutaneous injection. After injection of 50, 100 and 200 anti-fXaU./kg BW t50 values of 81, 123 and 182 minutes were calculated. According to this, with increasing dosage a decrease of the total clearance was found for both application routes. The apparent volume of distribution after intravenously applicated LMWH ranged between 50 and 70 ml/kg BW. The absolute bioavailability calculated for the subcutaneous NMH-injection of 50 and 100 anti-fXaU./kg BW was 107% and 104%, respectively.  相似文献   

11.
The objective of this study was to investigate the relationship between different screening tests of haemostasis and amidolytic plasma activities of unfractionated (standard) heparin in dogs. Different doses of intravenous (i.v.) [25, 50 or 100 IU Kg(-1)bodyweight (BW)] and subcutaneous (s.c.) heparin (250, 500 and 750 IU kg(-1)) were given to groups each of five clinically healthy adult beagles. Measurements of heparin activity with a factor Xa-dependent chromogenic substrate, activated partial thromboplastin time (APTT) (two different reagents), thrombin time (TT, two different thrombin activities in the reagent: 3 and 6 IU ml(-1)) and the reaction time of the resonance thrombogram (RTG -r) with two different measuring devices were performed at different times. The relationship between ratio values (actual/baseline values) of the coagulation tests and heparin activity was analysed based on regression analysis and correlation coefficient.The greatest alterations were seen for the TT([3 IU ml(-1)])and the RTG -r which were near or exceeded the upper limit of measuring range, if 25 IU kg(-1)BW heparin were given i.v. at heparin plasma levels of 0.54 +/- 0.13 IU ml(-1). These results show, that only APTT and TT measured with high thrombin activity assay appear suitable for guiding high dose heparin therapy in dogs. Averaged alterations of APTT ratio in canine plasma were less than those observed in people for similar plasma heparin levels, indicating that the guideline extrapolated from people for monitoring high dose heparin therapy using APTT may not be valid for use in dogs.After coagulation times had been converted into ratio values, based on regression analysis and Wilcoxon's test, differences of heparin sensitivity were found not only for TT measured with different thrombin activities but also for different APTT reagents (P < 0.001). The correlation between amidylotic antifactor Xa activity and ratio of coagulation times was only moderate and found to be lower for RTG -r (instrument 1: r(s)= 0.711; instrument 2: r(s)= 0.573) than for the other coagulation tests (r(s)= 0.822 to r(s)= 0.890). This indicates a considerable variability of the ratio values of the screening tests at defined heparin plasma activities. These results show, that blood coagulation tests in general are little or unsuitable for heparin antifactor-Xa activity control.  相似文献   

12.
The aim of this study was to test the efficacy of different dosages of low molecular weight heparin (LMWH) in acute DIC which was induced in anaesthetised dogs by 4 h infusions of a canine lung thromboplastin extract. In all animals during the first 2 h, development of acute DIC was characterised by decreasing fibrinogen concentrations, platelet numbers, factor V- and antithrombin activities. Two hours after starting the thromboplastin infusion, intravenous LMWH treatment in different dosages started in groups 2 and 3 to achieve plasma levels between 0.27+/-0.01 and 0.36+/-0.02 anti-FXaUml(-1) or 0.62+/-0.08 and 0.90+/-0.07 antiFXaUml(-1) (mean+/-SD), respectively, during the time period of parallel administration of thromboplastin and LMWH (group 1=control; 4 dogs/group). In this time period, changes in factor V activity and fibrinogen concentration did not differ between group 2 and the control group. This was in contrast to group 3. The results of this study indicate that an efficacious interruption of the consumption reaction in cases of severe canine DIC requires high plasma heparin levels.  相似文献   

13.
BACKGROUND: Heparin treatment has been recommended for dogs in hypercoagulable states such as disseminated intravascular coagulation, however, potential benefits have to be balanced against the bleeding risk if overdosage occurs. A better understanding of the pharmacology of heparin and tests to monitor heparin therapy in dogs may help prevent therapeutic hazards. OBJECTIVES: The purpose of this study was to evaluate the effects of 200 U/kg of sodium unfractionated heparin (UFH) on coagulation times in dogs after intravenous (IV) and subcutaneous (SC) administration and to compare these effects with plasma heparin concentrations assessed by its antifactor Xa (aXa) activity. METHODS: 200 U/kg of UFH were administered IV and SC to 5 healthy adult Beagle dogs with a washout period of at least 3 days. Activated partial thromboplastin time (APTT), prothrombin time (PT), and plasma aXa activity were determined in serial blood samples. RESULTS: After IV injection, PT remained unchanged except for a slight increase in 1 dog; APTT was not measurable (>60 seconds) for 45-90 minutes, and then decreased gradually to baseline values between 150 and 240 minutes. High plasma heparin concentrations were observed (maximal concentration = 4.64 +/-1.4 aXa U/mL) and decreased according to a slightly concave-convex pattern on a semilogarithmic curve, but returned to baseline slightly more slowly (t240-t300 minutes) than did APTT. After SC administration, APTT was moderately prolonged (by a ratio of 1.55 +/-0.28 APTT t0, range 1.35-2.01) between 1 and 4 hours after administration. Plasma aXa activity reached a maximum of 0.56 +/-0.20 aXa U/mL (range 0.42-0.9 U/mL) after 132 +/-26.8 minutes; this lasted for 102 +/-26.8 minutes. Prolongation of APTTs of 120-160% corresponded to plasma heparin concentrations of 0.3-0.7 aXa U/mL. CONCLUSIONS: As in humans, the pharmacokinetics of UFH in dogs was nonlinear. Administration of 200 U/kg of UFH SC in healthy dogs resulted in sustained plasma heparin concentrations in accordance with human recommendations for thrombosis treatment or prevention, without excessively increased bleeding risks. In these conditions, APTT can be used as a surrogate to assess plasma heparin concentrations. These findings need to be confirmed in diseased animals.  相似文献   

14.
BACKGROUND: There is considerable variation in the coagulation profile of dogs with disseminated intravascular coagulation (DIC), making it difficult to assess overall hemostatic function. OBJECTIVES: To characterize the overall hemostatic state in dogs with DIC, by use of tissue factor-activated thromboelastography (TF-TEG), and to determine whether there is an association between hemostasis and outcome. ANIMALS: 50 dogs with DIC. METHODS: Dogs admitted to the intensive care units, with an underlying disease known to predispose to DIC, were prospectively assessed with TF-TEG. Citrated blood samples were collected daily during hospitalization and an extended coagulation panel and TF-TEG were performed. Diagnosis of DIC was based on expert opinion. RESULTS: Hemostatic dysfunction was observed on the TF-TEG profile in 33/50 of the dogs, of which 22/50 were hypercoagulable and 11/50 were hypocoagulable based on the TF-TEG G value alone. There were significant differences in k, alpha, and MA values (P < .0001) among hypo-, normo-, and hypercoagulable dogs. There was a significant difference in case fatality rate between hypo- (64%) and hypercoagulable (32%) dogs (relative risk = 2.38; P= .04). Dogs that died had significantly lower antithrombin activity (P= .03) and higher d-dimer concentration (P= .03) than survivors. CONCLUSIONS: The most common overall hemostatic abnormality in dogs diagnosed with DIC was hypercoagulability, and there was significant difference in survival between hyper- and hypocoagulable dogs. The results suggest TF-TEG is valuable in the assessment of hemostatic function in dogs diagnosed with DIC.  相似文献   

15.
The aim of the study was to examine how activated partial thromboplastin time (APTT, two different reagents), thrombin time (TT, thrombin activity in the reagent: 3 or 6 IU ml(-1)) and reaction time of the resonance thrombogram (RTG-r) in healthy dogs are influenced by low molecular weight heparin (LMWH). Three different LMWH doses were given subcutaneously or intravenously to groups, each of five healthy dogs. Mean plasma anti-FXa activities of 0.43, 0.88 and 1.86 anti-FXa IU ml(-1)were measured 2 min after intravenous injection of 25, 50 or 100 anti-FXa IU kg(-1). At this time, a dose-dependent increase of the coagulation times, above the baseline values (P < 0.05), was observed for all haemostatic tests. The significant prolongation of coagulation time lasted 10 minutes to 3 hours, and it was dependent on the test employed and LMWH dose. After subcutaneous LMWH injection of 50, 100 and 200 anti-FXa IU kg(-1), significant changes of the coagulation time above initial values were limited to the period around the time when maximum anti-FXa activities (0.23, 0.43 or 0.90 anti-FXa IU ml(-1)) were observed. For the tests which were less affected by the LMWH (APTT, TT([6 IU ml)(-1)(])), only small increases (< 4 seconds) were observed even after the highest subcutaneous LMWH dose. The correlation between plasma heparin activity and the relative alteration compared to the initial value (ratio), of the different coagulation tests was only moderate and considerably lower for RTG-r (r(s)= 0.526) than for the TT (r(s)= 0.711([6 IU ml(-1)]), r(s)= 0.780([3 IU ml(-1)])) and APTT (r(s)= 0.667([reagent 1]), r(s)= 0.727([reagent 2])). The low degree of prolongation, which was found particularly for the group tests APTT and TT([6 IU ml)(-1)]), reflects the low anti-thrombin activity of LMWH. The results indicate that measurement of anti-FXa activity with chromogenic substrates is the method of choice to control LMWH therapy in dogs, as is the case in humans. Copyright2000 Harcourt Publishers Ltd Copyright 2000 Harcourt Publishers Ltd.  相似文献   

16.
This study assessed the effect of a vitamin E supplement given to pregnant mares on immunoglobulins (Ig) levels in foals. In addition, the fatty acid (FA) content and composition of the mares’ milk was assessed. Milk α‐tocopherol concentrations were compared between pregnant Danish Warmblood mares (n = 17) given a daily oral supplement of 2500 international units (IU) RRR‐α‐tocopherol in the last 4 weeks of pregnancy and a group of unsupplemented mares (n = 17) receiving 170–320 IU vitamin E daily originating from the feed. Milk α‐tocopherol was higher in supplemented mares (36.7, 12.4 and 9.8 μmol/l respectively) in relation to control mares (13.1, 6.4 and 5.8 μmol/l on days 1, 2 and 3 respectively; p < 0.001). Milk IgG was higher on days 2 and 3 post‐partum (PP) in supplemented mares (1.03 and 0.73 mg/ml respectively) in relation to control mares (0.79 and 0.56 mg/ml respectively; p < 0.05). Milk IgM was higher on days 2 and 3 post‐partum (PP) in supplemented mares (0.19 and 0.17 mg/ml) in relation to control mares (0.13 and 0.11 mg/ml respectively; p < 0.05). Plasma α‐tocopherol in foals was higher from supplemented mares on days 1, 2 and 3 (5.7, 14.8 and 19.2 μmol/l respectively) in relation to foals from control mares (3.6, 6.1 and 7.6 respectively; p < 0.001). Foal plasma IgM was higher from supplemented mares on day 3 (0.50 mg/ml) in relation to foals from control mares (0.32 mg/ml; p < 0.001). The total FA content in milk was highest on day 1 (21.6 g FA/kg milk) in relation to days 2 and 3 (13.6 and 13.5 g FA/kg milk respectively; p < 0.001). In conclusion, a daily oral supplement of 2500 IU RRR‐α‐tocopherol increased α‐tocopherol content in mare milk and foal plasma, IgG and IgM in mare milk and IgM in foal plasma.  相似文献   

17.
REASONS FOR PERFORMING STUDY: Unfractioned heparin (UFH) is widely used for prophylaxis of coagulation disorders, especially in colic-affected horses. However, it is accompanied by certain side effects. OBJECTIVES: To compare the efficacy and side effects of unfractioned and low molecular weight heparin (LMWH) in horses with colic. METHODS: The study was carried out as a randomised, double-blind, controlled clinical trial. Fifty-two horses with colic were treated subcutaneously with either UFH (heparin calcium, 150 iu/kg bwt initially, followed by 125 iu/kg bwt q. 12 h for 3 days and then 100 iu/kg bwt q. 12 h) or LMWH (dalteparin, 50 iu/kg bwt q. 24 h). All horses underwent daily physical examination including assessment of jugular veins, local reaction to heparin injections, haematological evaluation and coagulation profiles over up to 9 days. RESULTS: The type of heparin used did not affect the general behaviour and condition. There were significantly more jugular vein changes in horses treated with UFH. Packed cell volume decreased significantly within the first few days of UFH treatment, but did not change significantly in horses treated with LMWH. Activated partial thromboplastin time (aPTT) and thrombin time (TT) were prolonged in horses treated with UFH but not in those treated with LMWH. CONCLUSIONS: It was concluded that, in comparison to UFH, LMWH has markedly fewer side effects in horses. POTENTIAL RELEVANCE: Therefore, LMWH is recommended for prophylaxis of coagulation disorders in colic patients.  相似文献   

18.
Background: Increased synovial fibrinolytic activity (detected by increases in synovial D‐Dimer concentrations) has been observed in different joint diseases in humans and adult horses, presumably in order to minimize fibrin deposition within the joint and thus avoid its detrimental effects. Objective: To investigate fibrinolytic pathway activation in joint sepsis in foals by measuring synovial D‐Dimer concentrations. Animals: Eighteen septic foals with septic joints, 9 septic foals without septic joints, 9 systemically healthy foals with septic joint, and 3 controls are included. Methods: Prospective observational clinical study of foals admitted for septic arthritis. Synovial D‐Dimer concentration and routine synovial fluid analysis were performed. Diagnosis of joint sepsis was made whenever synovial total nucleated cell count was >30,000 cells/μL, synovial total protein >4 g/dL, and neutrophil percentage of >80%, or synovial fluid culture resulted positive. Results were compared among groups by general lineal models. Results: Synovial D‐Dimer concentration was significantly (P < .001) higher in the foals with septic joints compared with foals without joint disease (P < .001). Conclusions and Clinical Importance: Septic joint disease is associated with a marked increase of synovial D‐Dimer concentration (marked activation of the fibrinolytic activity) within the affected joint. Although further studies are needed, the measurement of synovial D‐Dimer concentration may be considered a complementary diagnostic marker of septic joint disease.  相似文献   

19.
Heparin: A Review of its Pharmacology and Therapeutic Use in Horses   总被引：2，自引：1，他引：1  
Heparin is used clinically in horses to treat hemostatic abnormalities associated with severe gastrointestinal disease, septicemia, and endotoxemia. The primary anticoagulant effect of heparin is through the suppression of thrombin-dependent amplification of the coagulation cascade, and inhibition of thrombin-mediated conversion of fibrinogen to fibrin. Heparin may be of benefit in preventing the complications associated with hypercoagulable states such as jugular vein thrombosis, laminitis, and organ failure. Heparin may also be beneficial in the prevention of intraabdominal adhesions after gastrointestinal surgery, and in amelioration of hemodynamic abnormalities associated with endotoxic shock. Because a sequential rise in serumheparin concentration occurs during a uniform dosage regimen, a decreasing dosage regimen is recommended. The initial dose recommended is 150 U heparin/kg body weight subcutaneously, followed by 125 U heparin/kg body weight subcutaneously, every 12 hours for six doses. The dose should be decreased to 100 U heparin/kg body weight subcutaneously, every 12 hours, after the seventh dose. Anemia, hemorrhage, thrombocytopenia, and painful swelling at injection sites are complications of heparin administration in horses.  相似文献   

20.
Background: Vinblastine (VBL) is commonly used in dogs at a dosage of 2.0 mg/m2. The minimal toxicity observed at this dosage indicates that higher dosages might be well tolerated. Hypothesis: The maximum tolerated dosage (MTD) for a single VBL treatment is higher than the previously published dosage of 2.0 mg/m2. Animals: Twenty‐three dogs with lymphoma or cutaneous mast cell tumors. Methods: Dogs received 1 single‐agent VBL treatment IV. The starting dosage was 3.0 mg/m2, and dosages were increased in increments of 0.5 mg/m2 in cohorts of 3 dogs. Hematologic toxicity was assessed with weekly CBCs. Gastrointestinal toxicity was assessed from medical histories from owners. Once the MTD was determined, additional dogs were treated with VBL at that dosage. Dogs whose cancers responded to VBL continued to receive treatments q2–3 weeks. Results: VBL dosages ranged from 3.0 to 4.0 mg/m2. Neutropenia was the dose‐limiting toxicity, with the nadir identified 7 days after treatment and resolving by 14 days after treatment. The MTD was 3.5 mg/m2. Sixteen dogs were treated at this dosage, and 3 experienced severe toxicity characterized by asymptomatic grade 4 neutropenia, febrile grade 4 neutropenia, and death. Gastrointestinal toxicity was mild and self‐limiting. Preliminary evidence of antitumor activity was identified in 2 of 12 dogs with lymphoma treated at the MTD. Conclusions and Clinical Importance: In dogs, single‐agent VBL is well tolerated at a dosage of 3.5 mg/m2 IV. At this dosage, the minimum safe treatment interval is q2 weeks, and adjunct treatment with prophylactic antibiotics should be considered.  相似文献   

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