OBJECTIVE To determine a treatment protocol for SC administration of dalteparin to cats on the basis of currently available detailed pharmacokinetic data and to assess the effect of SC administration of dalteparin to cats on coagulation variables such as activated partial thromboplastin time (aPTT), thrombin time, and results for thromboelastometry, compared with effects on anti–activated coagulation factor X (anti-Xa) activity. ANIMALS 6 healthy domestic shorthair cats. PROCEDURES Cats received 14 injections of dalteparin (75 anti-Xa U/kg, SC) at 6-hour intervals. Blood samples were collected before and 2 hours after the first and second injections on days 1, 2, and 4. Anti-Xa activity was measured by use of a chromogenic substrate assay, aPTT and thrombin time were measured by use of an automated coagulometer, and viscoelastic measurements were obtained with thromboelastrometry. RESULTS 2 hours after the second injection, the target peak anti-Xa activity range of 0.5 to 1.0 U/mL was achieved in all cats, whereas median trough values remained below this range. Peak anti-Xa activity had only minimal effects on coagulation variables; the maximum median ratio for aPTT (in relationship to the value before the first dalteparin injection) was 1.23. CONCLUSIONS AND CLINICAL RELEVANCE Results of this study indicated that this treatment protocol resulted in reproducible anti-Xa activity in cats that was mostly within the targeted peak range of anti-Xa activity recommended for humans. Treatment in accordance with this protocol may not require routine coagulation monitoring of cats, but this must be confirmed in feline patients.

Objective: To investigate the in vitro effects of 3 hydroxyethyl starch (HES) solutions on viscoelastic coagulation testing and platelet function in horses. Sample: Blood samples collected from 7 healthy adult horses. Procedures: Blood samples were diluted with various crystalloid and HES solutions to approximate the dilution of blood in vivo that occurs with administration of a 10 and 20 mL/kg fluid bolus to a horse (1:8 and 1:4 dilutions, respectively). Diluted samples were analyzed through optical platelet aggregometry, platelet function analysis, thromboelastography, and dynamic viscoelastic coagulometry. Colloid osmotic pressure and concentrations of von Willebrand factor and factor VIII:C were also determined for each sample. Results: For all HES products, at both dilutions, the colloid osmotic pressure was significantly higher than that in the respective carrier solutions. At the 1:4 dilution, nearly all HES solutions resulted in significant alterations in platelet function as measured via the platelet function analyzer and dynamic viscoelastic coagulometer. Significant decreases in platelet aggregation and factor concentrations were also evident. Fewer HES-associated changes were identified at the 1:8 dilutions. Conclusions and Clinical Relevance: Dilution of blood samples with all HES solutions resulted in changes in viscoelastic coagulation and platelet function that did not appear to be attributable to dilution alone. In vivo evaluations are necessary to understand the clinical impact of these in vitro changes.

Objective: To evaluate the pharmacodynamic effects of dalteparin in dogs by means of viscoelastic coagulation monitoring with a thromboelastograph and a dynamic viscoelastic coagulometer. Animals: 6 healthy adult mixed-breed dogs. Procedures: Dalteparin (175 U/kg, SC, q 12 h) was administered for 4 days (days 1 through 4). Viscoelastic coagulation monitoring was performed hourly on the first and last days of treatment and included intermittent measurement of anti–activated coagulation factor X activity (AXA). Results: Dalteparin administration resulted in progressive hypocoagulability. On both day 1 and 4, activated clotting time and clot rate for the dynamic viscoelastic coagulometer differed significantly from baseline values, whereas the platelet function parameter did not change on day 1 but did on day 4. The R (reaction time), time from reaction time until the amplitude of the thromboelastography tracing is 20 mm, α-angle, and maximum amplitude differed from baseline values on days 1 and 4, although many thromboelastographic variables were not determined. The AXA was increased from baseline values at 3 and 6 hours after administration of the dalteparin injection on days 1 and 4, and all dogs had AXA values between 0.5 and 1.0 U/mL at 2 and 4 hours after administration. The AXA correlated well with activated clotting time (r = 0.761) and with R (r = 0.810), when values were available. Thromboelastography could not be used to distinguish AXA > 0.7 U/mL. Conclusions and Clinical Relevance: Viscoelastic coagulation monitoring with strong coagulation activators may be used to monitor treatment with dalteparin in healthy dogs.

OBJECTIVE To assess feasibility of the use of a dynamic viscoelastic coagulometer on chicken blood and compare coagulation variables for fresh whole blood and sodium citrate–preserved whole blood as well as effects of 3 coagulation activators on blood from chickens. SAMPLE Blood samples from 30 hens. PROCEDURES Chickens were allowed to rest undisturbed for 1 hour. A blood sample was collected from an ulnar vein; 1.4 mL was analyzed immediately, and 1.8 mL was mixed with sodium citrate and subsequently recalcified and analyzed. A separate coagulation activator (glass beads, kaolin clay, or tissue factor) was in each of the 2 channels of the analyzer. Chickens were allowed a 1-hour rest period, and another blood sample was collected from the contralateral ulnar vein; it was processed in the same manner as for the first sample, except both channels of the analyzer contained the same coagulation activator. RESULTS Compared with fresh samples, citrated samples had higher values for activated clotting time and platelet function and lower clotting rates. Intra-assay coefficients of variation of coagulation profiles for citrated samples were markedly greater than the limit of 10%, whereas values for fresh samples were close to or < 10%. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that use of a dynamic viscoelastic coagulometer on chicken blood was feasible and that analysis of fresh whole blood from healthy chickens provided results with less variability than did analysis of citrated blood. Samples preserved with sodium citrate were associated with significant relative hypocoagulability, compared with results for fresh blood.

Objective: To describe the effect of systemically administered oxytetracycline on the viscoelastic properties of rat tail tendon fascicles (TTfs) to provide a mechanistic rationale for pharmacological treatment of flexural limb deformities in foals. Sample: TTfs from ten 1-month-old and ten 6-month-old male Sprague-Dawley rats. Procedures: 5 rats in each age group were administered oxytetracycline (50 mg/kg, IP, q 24 h) for 4 days. The remaining 5 rats in each age group served as untreated controls. Five days after initiation of oxytetracycline treatment, TTfs were collected and their viscoelastic properties were evaluated via a stress-relaxation protocol. Maximum modulus and equilibrium modulus were compared via a 2-way ANOVA. Collagen fibril size, density, and orientation in TTfs were compared between treated and control rats. Results: Viscoelastic properties were significantly decreased in TTfs from 1-month-old oxytetracycline-treated rats, compared with those in TTfs from 1-month-old control rats. Oxytetracycline had no effect on the viscoelastic properties of TTfs from 6-month-old rats. Collagen fibril size, density, and orientation in TTfs from 1-month-old rats did not differ between oxytetracycline-treated and control rats. Conclusions and Clinical Relevance: Results confirmed that systemically administered oxytetracycline decreased the viscoelastic properties of TTfs from 1-month-old rats but not those of TTfs from 6-month-old rats. The decrease in viscoelastic properties associated with oxytetracycline treatment does not appear to be caused by altered collagen fibril diameter or organization. The age-dependent effect of oxytetracycline on the viscoelastic properties of tendons may be related to its effect on the maturation of the extracellular matrix of developing tendons.

OBJECTIVE To determine whether differences existed in the viscoelastic properties of synovial fluid samples from the metacarpophalangeal, intercarpal, and distal interphalangeal joints of orthopedically normal athletic horses. ANIMALS 45 warmblood horses and 30 Thoroughbreds (age range, 4 to 16 years). PROCEDURES Synovial fluid samples were aseptically obtained via arthrocentesis from 1 metacarpophalangeal, intercarpal, and distal interphalangeal joint of each horse, and nucleated cell counts were performed. A commercial ELISA was used to measure sample hyaluronic acid concentrations, and full rheological characterization of samples was performed to measure the elastic or storage modulus G' and viscous or loss modulus G“ at 37.5°C (representing the body temperature of horses). Findings were compared among joints and between breed groups by means of ANOVA. RESULTS Significant differences in synovial fluid G' and G“ values were identified between Thoroughbreds and warmblood horses for the metacarpophalangeal joint, between the metacarpophalangeal and intercarpal joints of Thoroughbreds, and between the metacarpophalangeal and distal interphalangeal joints and intercarpal and distal interphalangeal joints of warmblood horses. No significant differences were identified between breed groups or among joints in synovial fluid hyaluronic concentrations or nucleated cell counts. CONCLUSIONS AND CLINICAL RELEVANCE Viscoelastic properties of the forelimb joints of orthopedically normal Thoroughbreds and warmblood horses differed within and between these 2 groups, mainly as a function of the evaluated joint. To the authors' knowledge, this was the first study of its kind, and additional research is warranted to better understand the viscoelastic properties of synovial fluid in horses to optimize their locomotive function.