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

2.
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   

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: Unfractionated heparin (UFH) has a complex pharmacologic profile that necessitates patient monitoring to prevent inadequate anticoagulation or overdosage and hemorrhage. Factor Xa inhibitory assays (to measure anti-Xa activity) are used to adjust UFH dosage and define safe and effective regimens for specific thrombotic disorders in humans. OBJECTIVE: In this study, the accuracy, linearity, and clinical utility of a chromogenic assay were assessed for monitoring UFH anti-Xa activity in canine plasma samples. METHODS: A commercial assay (Rotachrom Heparin, Diagnostica Stago, Parsippany, NJ, USA) was used to measure anti-Xa activity in canine plasma samples spiked with different concentrations of UFH. Background absorbance and assay linearity were compared for canine and human plasmas. Percentage recovery of UFH anti-Xa activity and intra- and interassay imprecisions were investigated by multiple measurements of canine plasma to which known amounts of UFH were added. The spiked plasma samples also were used to determine the heparin sensitivity of an activated partial thromboplastin time (aPTT) test. RESULTS: Canine plasma samples were assayed at a higher dilution than were human plasma samples (3:8 versus 4:8) to eliminate higher background anti-Xa activity in canine plasma. Using this modification, the recovery of anti-Xa activity in canine plasma was linear (R2 > .9) at concentrations of 0 - 0.75 U/mL UFH. Intra- and interassay imprecisions for plasma samples containing 0.5 U/mL UFH were <10%, whereas samples containing 0.25 U/mL UFH had imprecisions of 13% and 24%, respectively. The anti-Xa activity range of 0.5 - 0.75 U/mL caused prolongation of aPTTs to 1.5 - 2.5 times the assay mean. CONCLUSION: Plasma anti-Xa activity of dogs treated with UFH can be accurately monitored using this commercially available chromogenic assay.  相似文献   

5.
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   

6.
Background: Systemic arterial thromboembolic events are a serious complication of cardiac disease in cats.
Objectives: To determine if enoxaparin induces an antithrombotic effect in cats at a dosage of 1 mg/kg SC q12h and if this antithrombotic effect is predicted by anti-Xa activity.
Animals: Fourteen clinically healthy cats were divided into 3 groups: control (4 cats), treated and assessed at 4 hours (5 cats), and treated and assessed at 12 hours (5 cats).
Methods: A venous stasis model was used and the extent of thrombus formation estimated by measuring thrombus weight and accretion of 125I-fibrinogen. Plasma anti-Xa activity was measured in treated cats.
Results: There was a significant reduction in thrombus formation in the 4 h group compared with control (median weight, 0.000 versus 0.565 mg/mm, P < .01; median %125I-fibrinogen accretion, 0.0 versus 42.0%, P < .01). There was a reduction in thrombus formation in the 12 h group (median weight, 0.006 mg/mm, P = .09; median %125I-fibrinogen accretion, 3.83%, P = .09) but this reduction was not significant. The median percent thrombus inhibition for treated cats was 100.0% at 4 hours and 91.4% at 12 hours. Plasma anti-Xa activity was not significantly correlated with thrombus formation.
Conclusions and Clinical Importance: This pilot study demonstrates that enoxaparin, when administered at a dosage of 1 mg/kg SC q12h, produces an antithrombotic effect in a venous statsis model in clinically healthy cats. Furthermore, this study demonstrates that anti-Xa activity is a poor predictor of enoxaparin's antithrombotic effect.  相似文献   

7.
Objective – Compare the effects of 3 anticoagulation protocols on anti-factor Xa activity (AXa).
Design – Prospective, randomized, double-blind study.
Setting – University veterinary teaching hospital.
Animals – Eighteen dogs considered to be at risk for venous thrombosis.
Interventions – Each dog was randomly assigned to 1 of the following 3 groups ( n =6/group) and was treated for 24 hours: low-dose heparin (LDH), high-dose heparin (HDH), and dalteparin (DP). Dogs in the LDH group received a constant rate infusion (CRI) of unfractionated heparin (UFH) at 300 U/kg/d, the HDH group received a bolus of 100 U/kg of UFH IV, then a CRI of 900 U/kg/day, and the DP group received 100 U/kg DP SC at 0, 12, and 24 hours.
Measurements and Main Results – A total of 54 samples for activated partial thromboplastin time (aPTT) and AXa assays were collected at 0, 4, and 28 hours. Six samples had an AXa >0.1 U/mL, 5 of those were from the HDH group at hour 4. Two samples from the HDH group at hour 4 had a prolonged aPTT (93 and 200 seconds) and the highest AXa (0.6 and 1.0 U/mL, respectively). Four additional dogs in the HDH group did not complete the study due to hemorrhage; none of the dogs completing the study showed signs of hemorrhage.
Conclusions: Neither DP nor LDH increased AXa to values considered therapeutic in humans (0.5–1 and 0.35–0.75 U/mL, respectively), and both protocols appear to be inadequate to increase AXa in dogs with clinical illness. HDH increased AXa to this range in 2 of 6 dogs, but had unpredictable effects on aPTT and resulted in hemorrhage in some dogs.  相似文献   

8.
OBJECTIVE: To determine pharmacokinetic variables and to evaluate the influence on clotting times after SC administration of single doses of dalteparin and enoxaparin to horses. ANIMALS: 5 healthy adult horses. PROCEDURES: The study was designed as a 4-period crossover study. Each horse received a single SC injection of dalteparin (50 and 100 anti-Xa U/kg) and enoxaparin (40 and 80 anti-Xa U/kg). Plasma anti-Xa activities and clotting times were measured, and pharmacokinetic variables were determined. Absolute and relative maximal prolongation of clotting times was calculated, and correlation between plasma anti-Xa activities and clotting times was determined. RESULTS: The SC administration of each of the doses of the 2 preparations was well tolerated. Time course of the anti-Xa activities could be described in a 1-compartment model. Comparison of low- and high-dose treatments revealed a disproportionate increase of the area under the plasma activity-time curve and prolongation of the terminal half-life, but the increase in maximum plasma activity was proportionate, and peak plasma concentrations corresponded with concentrations recommended in human medicine. There were only mild changes in activated partial thromboplastin time (aPTT), whereas the influence on thrombin time (TT) was greater, dose-dependent, and more variable. A weak-to-moderate correlation between aPTT and plasma anti-Xa activities and a moderate-to-strong correlation between TT and plasma anti-Xa activities were found. CONCLUSIONS AND CLINICAL RELEVANCE: Pharmacokinetic and anticoagulatory properties of low-molecular-weight heparins in horses are similar to those found in humans. Once-daily SC administration of dalteparin or enoxaparin may be useful as an anticoagulatory treatment in horses.  相似文献   

9.
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   

10.
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   

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