Egg reappearance periods of anthelmintics against equine cyathostomins: The state of play revisited.

Cyathostomins are the most common and highly prevalent parasites of horses worldwide. Historically, the control of cyathostomins has mainly relied on the routine use of anthelmintic products. Increasing reports on anthelmintic resistance (AR) in cyathostomins are concerning. A potential method proposed for detecting emerging AR in cyathostomins has been estimating the egg reappearance period (ERP). This paper reviews the data available for the ERP of cyathostomins against the three major classes of anthelmintics, macrocyclic lactones, tetrahydropyrimidines, and benzimidazoles. Published peer-reviewed original research articles were obtained from three databases (PubMed, CAB Direct and Web of Science) and were evaluated for their inclusion in a systematic review. Subsets of articles were then subjected to a review of ERP data. A total of 54 (of 134) studies published between 1972 and 2022 met the criteria for inclusion in the systematic review. Until the beginning of 2022, there was no agreed definition of the ERP; eight definitions of ERP were identified in the literature, complicating the comparison between studies. Additionally, potential risk factors for the shortening of the ERP, including previous anthelmintic use and climate, were frequently not described. Reports of shortened ERP for moxidectin and ivermectin are frequent: 20 studies that used comparable ERP definitions reported shortened moxidectin and ivermectin ERPs of 35 and 28 days, respectively. It is unclear whether the ERPs of these anthelmintics reduced to such levels are due to the development of AR or some biological factors related to horses, cyathostomin species, and/or the environment. The ERPs for other anthelmintics, such as fenbendazole and pyrantel, were frequently not reported due to established resistance against these drugs. Future research in horses is required to understand the mechanism(s) behind the shortening of ERP for cyathostomins. Based on this systematic review, we propose recommendations for future ERP studies.

Molecular diagnostics for gastrointestinal helminths in equids: Past, present and future.

This review is aimed to (i) appraise the literature on the use of molecular techniques for the detection, quantification and differentiation of gastrointestinal helminths (GIH) of equids, (ii) identify the knowledge gaps and, (iii) discuss diagnostic prospects in equine parasitology. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews, we retrieved 54 studies (horses: 50/54; donkeys and zebras: 4/54) from four databases. Polymerase chain reaction (PCR) was employed in all of the studies whereas PCR amplicons were sequenced in only 18 of them. Other techniques used (including modifications of PCR) were reverse line blot, quantitative (q)PCR, restriction fragment length polymorphism, nested-PCR, PCR-directed next-generation sequencing, Southern blotting, single strand conformation polymorphism, PCR-enzyme linked immunosorbent assay, matrix-assisted laser desorption/ionisation-time of flight and random amplification of polymorphic DNA. Most of the studies (53/54) used nuclear ribosomal RNA (including the internal transcribed spacers, intergenic spacer, 5.8 S, 18 S, 28 S and 12 S) as target loci while cytochrome c oxidase subunit 1 and random genomic regions were targeted in only three and one studies, respectively. Overall, to date, the majority of molecular studies have focused on the diagnosis and identification of GIHs of equids (i.e. species of Anoplocephala, Craterostomum, cyathostomins, Oesophagodontus, Parascaris, Strongylus, Strongyloides and Triodontophorus), with a recent shift towards investigations on anthelmintic resistance and the use of high-throughput nemabiome metabarcoding. With the increasing reports of anthelmintic resistance in equid GIHs, it is crucial to develop and apply techniques such as advanced metabarcoding for surveillance of parasite populations in order to gain detailed insights into their diversity and sustainable control. To the best of our knowledge, this is the first systematic review that evaluates molecular investigations published on the diagnosis and quantification of equid GIHs and provides useful insights into important knowledge gaps and future research directions in equid molecular parasitology.

Cyathostomin resistance to moxidectin and combinations of anthelmintics in Australian horses.

BACKGROUND: Cyathostomins are the most important and common parasitic nematodes of horses, with > 50 species known to occur worldwide. The frequent and indiscriminate use of anthelmintics has resulted in the development of anthelmintic resistance (AR) in horse nematodes. In this study we assessed the efficacy of commonly used anthelmintics against cyathostomins in Australian thoroughbred horses. METHODS: Two drug efficacy trials per farm were conducted on two thoroughbred horse farms in the state of Victoria, Australia. In the first trial, the horses on Farm A were treated with single and combinations of anthelmintics, including oxfendazole (OFZ), abamectin (ABM), abamectin and morantel (ABM + MOR), moxidectin (MOX) and oxfendazole and pyrantel (OFZ + PYR), at the recommended doses, whereas the horses on Farm B only received MOX, at the recommended dose. The faecal egg count reduction test (FECRT) was used to determine the efficacy and egg reappearance period (ERP) of anthelmintics. Based on the results of the first trial, the efficacies of MOX and a combination of ABM + MOR were reassessed to confirm their activities against cyathostomins. RESULTS: Of the five anthelmintic products tested on Farm A, resistance against OFZ, ABM and OFZ + PYR was found, with efficacies of - 41% (- 195% lower confidence limit [LCL]), 73% (60% LCL) and 82% (66% LCL) at 2 weeks post-treatment, respectively. The FECRT showed high efficacies of MOX and ABM + MOR (100%) at 2 week post-treatment and shortened ERPs for these anthelmintics (ABM + MOR: 4 weeks; MOX: 5 weeks). Resistance to MOX was found on Farm B, with a reduced efficacy of 90% (70% LCL) and 89% (82% LCL) at 2 weeks post-treatment in trials one and two, respectively. CONCLUSIONS: This study provides the first evidence of MOX- and multidrug-resistant (ABM and combinations of anthelmintics) cyathostomins in Australia and indicates the need for continuous surveillance of the efficacy of currently effective anthelmintics and large-scale investigations to assess the ERP for various anthelmintics.

Molecular detection of Strongyloides sp. in Australian Thoroughbred foals.

BACKGROUND: Strongyloides westeri is found in the small intestine of young horses, mainly in foals up to about 16 weeks of age. The main source of infection for foals is through transmammary transmission, and foals can develop acute diarrhoea, weakness, dermatitis and respiratory signs. The epidemiology of S. westeri in Australia is largely unknown. Further, molecular techniques have never been employed for detection of S. westeri in horses. This pilot study aimed to assess the utility of a molecular phylogenetic method for the detection of S. westeri in the faeces of foals. METHODS: Faecal samples were collected from a foal of less than 2 months of age, and eggs of Strongyloides sp. were detected using the modified McMaster technique. DNA was extracted from purified eggs, and a partial fragment of the small subunit of the nuclear ribosomal DNA (18S) was characterised using polymerase chain reaction, DNA sequencing and phylogenetic methods. RESULTS: Microscopic examination of faeces revealed small ellipsoidal eggs typical of Strongyloides sp. The 18S sequence generated by PCR in this study revealed 98.4% identity with that of a reference sequence of S. westeri available from GenBank. Phylogenetic analyses revealed a polyphyletic clustering of S. westeri sequences. CONCLUSION: This is the first study reporting the detection of DNA of Strongyloides sp. in faeces of a foal using a molecular phylogenetic approach targeting the variable region of 18S rDNA. It is anticipated that this study will allow future molecular epidemiological studies on S. westeri in horses.

Fibrinogen heterogeneity in horses.

BACKGROUND: Fibrinogen heterogeneity has been observed in humans and can influence fibrinogen measurements when using the modified Clauss assay. We hypothesized that fibrinogen heterogeneity also exists in horses. OBJECTIVES: To determine whether fibrinogen heterogeneity exists in horses. ANIMALS: Five clinically healthy horses from the university equine teaching herd. METHODS: Presumed fibrinogen was purified from pooled citrated plasma and electrophoresis performed. The purified protein was subjected to Western blotting using sheep antiserum against human fibrinogen, and liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: Gel electrophoresis of nonreduced equine purified protein yielded 2 protein bands (approximately 377 and 318 kDa) that corresponded with the molecular weights of human high molecular weight fibrinogen and low molecular weight fibrinogen fractions, respectively. Electrophoretograms of reduced purified protein, Western blots, and LC-MS/MS supported that the purified nonreduced protein bands were fibrinogen. CONCLUSION: Fibrinogen heterogeneity exists in horses.

Comparative studies on faecal egg counting techniques used for the detection of gastrointestinal parasites of equines: A systematic review.

Faecal egg counting techniques (FECT) form the cornerstone for the detection of gastrointestinal parasites in equines. For this purpose, several flotation, centrifugation, image- and artificial intelligence-based techniques are used, with varying levels of performance. This review aimed to critically appraise the literature on the assessment and comparison of various coprological techniques and/or modifications of these techniques used for equines and to identify the knowledge gaps and future research directions. We searched three databases for published scientific studies on the assessment and comparison of FECT in equines and included 27 studies in the final synthesis. Overall, the performance parameters of McMaster (81.5%), Mini-FLOTAC® (33.3%) and simple flotation (25.5%) techniques were assessed in most of the studies, with 77.8% of them comparing the performance of at least two or three methods. The detection of strongyle, Parascaris spp. and cestode eggs was assessed for various FECT in 70.4%, 18.5% and 18.5% studies, respectively. A sugar-based flotation solution with a specific gravity of ≥1.2 was found to be the optimal flotation solution for parasitic eggs in the majority of FECT. No uniform or standardised protocol was followed for the comparison of various FECT, and the tested sample size (i.e. equine population and faecal samples) also varied substantially across all studies. To the best of our knowledge, this is the first systematic review to evaluate studies on the comparison of FECT in equines and it highlights important knowledge gaps in the evaluation and comparison of such techniques.

Urine creatinine concentration and urine protein-to-creatinine ratios in healthy nonracing Greyhounds.

BACKGROUND: Serum creatinine concentrations are higher in Greyhounds when compared with nonsighthound breeds. Greyhounds might also have higher urine creatinine concentrations compared with other breeds, which could affect urine protein-to-creatinine ratio (UPC) references. OBJECTIVES: We aimed to determine the UPC reference intervals (RIs) in healthy nonracing Greyhounds and compare this with UPC values in a group of healthy nonsighthounds and with the current International Renal Interest Society (IRIS) guidelines. METHODS: The study used an observational cross-sectional design, involving clinically healthy, nonracing Greyhounds (n = 98) and nonsighthound dogs of similar weight, age, and sex (n = 24). Packed cell volumes, total solids, urine protein concentrations, serum and urine creatinine concentrations, urine specific gravity (USG) measurements, and UPCs were determined. Linear regression was used to compare urine creatinine and urine protein concentrations, relative to the USG measurements, between Greyhound and nonsighthound groups. Greyhound UPC RIs were determined using nonparametric methods and compared with UPC values in nonsighthounds and current IRIS guidelines. RESULTS: Mean urine creatinine concentrations, adjusted for USGs, were approximately 22% higher in Greyhounds compared with nonsighthounds (P = .002). Mean urine protein concentration (P = .46) and UPC (P = .1) were not significantly different between Greyhounds and nonsighthounds. The upper limit of the Greyhound UPC RI was 0.20 or 0.42, depending on whether strict or moderate exclusion criteria were applied, respectively. CONCLUSIONS: Greyhounds have higher urine creatinine concentrations than nonsighthounds. Although the suggested RI for UPCs in Greyhounds is slightly lower than the cut-offs recommended in generic canine IRIS guidelines, this difference is not likely to be clinically significant.

In vitro effects of lactated Ringer's solution, hypertonic saline, hydroxyethyl starch, hypertonic saline/hydroxyethyl starch, and mannitol on thromboelastographic variables of canine whole blood.

OBJECTIVE: To assess the in vitro effects of crystalloid and colloid IV fluids on the thromboelastographic (TEG) variables of canine whole blood. DESIGN: In vitro experimental study. SETTING: Veterinary teaching hospital. ANIMALS: Twenty-two healthy dogs. INTERVENTION: Citrated whole blood samples collected from healthy dogs were diluted with 3.4% hypertonic saline (HTS 3.4), 7% hypertonic saline (HTS 7), and 20% mannitol at 8% and 16% dilutions; hydroxyethyl starch 130/0.4 (HES 130/0.4) at 16% dilution; lactated Ringer's solution (LRS) at 16%, 33%, and 66% dilutions; and HTS 7-HES 130/0.4 at 25% and 50% dilutions. Kaolin-activated TEG analysis was concurrently performed on diluted and control (undiluted) samples. MEASUREMENTS AND MAIN RESULTS: Dilution of canine whole blood with LRS compared to control reduced α angle and MA at both 33% (P = 0.009 and P = 0.011, respectively) and 66% dilution (P < 0.001 and P < 0.001, respectively), and prolonged K time at 66% dilution (P = 0.003). At 16% dilution, HTS 3.4, prolonged R time (P = 0.007), while mannitol, a fluid iso osmolar to HTS 3.4, prolonged K time (P = 0.006), reduced α angle (P < 0.001), MA (P = 0.046), and LY60 (P = 0.015). At 8% dilution, HTS 7, a fluid of high osmolarity and tonicity, prolonged R time (P = 0.009) and reduced MA (P = 0.015), while all measured TEG variables were altered at the 16% dilution (P < 0.01 for all variables). HES 130/0.4 reduced α angle (P = 0.031) and MA (P = 0.001) and increased LY60 (P < 0.001) at 16% dilution. Comparing different fluid types, HES 130/0.4 and HTS 3.4 had no to minor, mannitol intermediate, and HTS 7 profound effects on TEG variables (P < 0.05) when compared to LRS at the same dilution. CONCLUSIONS: In vitro dilution of canine whole blood with commonly used IV fluids leads to thromboelastographic changes consistent with hypocoagulability in a dose dependent manner for all fluid types tested. Viscoelastic changes are also influenced by fluid characteristics, specifically tonicity and osmolarity.

Anti-inflammatory effects of a p38 MAP kinase inhibitor, doramapimod, against bacterial cell wall toxins in equine whole blood.

Doramapimod (BIRB-796-BS), is an anti-inflammatory compound, acting through p38 MAPK inhibition, but its anti-inflammatory effects have not previously been studied in the horse. Whole blood aliquots from healthy horses diluted 1:1 with cell culture medium were incubated for 21 h with 1 µg/ml of lipopolysaccharide (LPS), lipoteichoic acid (LTA) or peptidoglycan (PGN) in the presence of increasing concentrations of doramapimod (3 × 10-8 M to 10-5 M). Cell bioassays were used to measure TNF-α and IL-1ß activity. Doramapimod significantly and potently inhibited TNF-α and IL-1ß activity induced by all three bacterial toxins. There was no significant difference in IC50 or maximum inhibition of TNF-α or IL-1ß production between any of the toxins. Maximum inhibition of IL-1ß was higher than that of TNF-α for all toxins, and this difference was significant for LPS (P = 0.04). Doramapimod was a potent inhibitor of TNF-α and IL-1ß for inflammation induced by LPS, LTA and PGN, with potency much greater than that of other drugs previously tested using similar methods.

Systematic review of gastrointestinal nematodes of horses from Australia.

BACKGROUND: Equine gastrointestinal nematodes (GINs) have been the subject of intermittent studies in Australia over the past few decades. However, comprehensive information on the epidemiology of equine GINs, the efficacy of available anthelmintic drugs and the prevalence of anthelmintic resistance (AR) in Australasia is lacking. Herein, we have systematically reviewed existing knowledge on the horse GINs recorded in Australia, and main aspects of their pathogeneses, epidemiology, diagnoses, treatment and control. METHODS: Six electronic databases were searched for publications on GINs of Australian horses that met our inclusion criteria for the systematic review. Subsets of publications were subjected to review epidemiology, diagnoses, pathogeneses, treatment and control of GINs of horses from Australia. RESULTS: A total of 51 articles published between 1950 to 2018 were included. The main GINs reported in Australian horses were cyathostomins (at least 28 species), Draschia megastoma, Habronema muscae, H. majus, Oxyuris equi, Parascaris equorum, Strongyloides westeri and Trichostrongylus axei across different climatic regions of Queensland, New South Wales, Victoria, and Western Australia. Nematodes are diagnosed based on the traditional McMaster egg counting technique, though molecular markers to characterise common GINs of equines were characterised in 1990s. The use of anthelmintic drugs remains the most widely-used strategy for controlling equine GIN parasites in Australia; however, the threshold of faecal egg count that should trigger treatment in horses, remains controversial. Furthermore, anthelmintic resistance within GIN population of horses is becoming a common problem in Australia. CONCLUSIONS: Although GINs infecting Australian horses have been the subject of occasional studies over the past few decades, the effective control of GIN infections is hampered by a generalised lack of knowledge in various disciplines of equine parasitology. Therefore, coordinated and focused research is required to fill our knowledge gaps in these areas to maximise equine health and minimise economic losses associated with the parasitic infections in Australia.

Establishment of reference intervals for serum symmetric dimethylarginine in adult nonracing Greyhounds.

BACKGROUND: The reference intervals (RIs) for the renal biomarkers urea and creatinine, in Greyhounds, are higher than those for non-sighthound breeds. A recent study has demonstrated a higher concentration of another biomarker of renal function, symmetric dimethylarginine (SDMA), in Greyhounds compared with other dog breeds, and thus a breed-specific RI for serum SDMA may be appropriate for Greyhounds. Greyhounds appear to be predisposed to renal disease, and the establishment of an appropriate RI for SDMA may improve the ability to identify early renal dysfunction in this breed. OBJECTIVES: The aim of this study was to establish an RI for serum SDMA in nonracing Greyhounds and to determine whether the RI for Greyhounds is different from that of non-sighthound breeds. METHODS: Blood samples were collected from 101 clinically healthy, nonracing Greyhounds for serum SDMA measurements. Results from Greyhounds were compared with serum SDMA concentrations measured in a group of non-sighthound dogs (n = 24) of similar weight, age, and sex, and with a previously established canine serum SDMA RI. RESULTS: The serum SDMA RI for Greyhounds was 6.3-19.9 µg/dL (0.31-0.99 µmol/L). Greyhounds had a significantly higher mean value (13.1 µg/dL) than that of the non-sighthound dogs (10.2 µg/dL) (P < .001), and the RI of Greyhounds was different from previously established canine RIs for SDMA. CONCLUSION: This study supports the use of a Greyhound-specific RI for SDMA. Using previously established canine RIs for this breed could result in the overdiagnosis of renal disease.

Clinical use of plasma lactate concentration. Part 1: Physiology, pathophysiology, and measurement.

OBJECTIVE: To review the current literature with respect to the physiology, pathophysiology, and measurement of lactate. DATA SOURCES: Data were sourced from veterinary and human clinical trials, retrospective studies, experimental studies, and review articles. Articles were retrieved without date restrictions and were sourced primarily via PubMed, Scopus, and CAB Abstracts as well as by manual selection. HUMAN AND VETERINARY DATA SYNTHESIS: Lactate is an important energy storage molecule, the production of which preserves cellular energy production and mitigates the acidosis from ATP hydrolysis. Although the most common cause of hyperlactatemia is inadequate tissue oxygen delivery, hyperlactatemia can, and does occur in the face of apparently adequate oxygen supply. At a cellular level, the pathogenesis of hyperlactatemia varies widely depending on the underlying cause. Microcirculatory dysfunction, mitochondrial dysfunction, and epinephrine-mediated stimulation of Na+ -K+ -ATPase pumps are likely important contributors to hyperlactatemia in critically ill patients. Ultimately, hyperlactatemia is a marker of altered cellular bioenergetics. CONCLUSION: The etiology of hyperlactatemia is complex and multifactorial. Understanding the relevant pathophysiology is helpful when characterizing hyperlactatemia in clinical patients.

Clinical use of plasma lactate concentration. Part 2: Prognostic and diagnostic utility and the clinical management of hyperlactatemia.

OBJECTIVE: To review the current literature pertaining to the use of lactate as a prognostic indicator and therapeutic guide, the utility of measuring lactate concentrations in body fluids other than blood or plasma, and the clinical management of hyperlactatemia in dogs, cats, and horses. DATA SOURCES: Articles were retrieved without date restrictions primarily via PubMed, Scopus, and CAB Abstracts as well as by manual selection. HUMAN AND VETERINARY DATA SYNTHESIS: Increased plasma lactate concentrations are associated with increased morbidity and mortality. In populations with high mortality, hyperlactatemia is moderately predictive in identifying nonsurvivors. Importantly, eulactatemia predicts survival better than hyperlactatemia predicts death. Consecutive lactate measurements and calculated relative measures appear to outperform single measurements. The use of lactate as a therapeutic guide has shown promising results in people but is relatively uninvestigated in veterinary species. Increased lactate concentrations in body fluids other than blood should raise the index of suspicion for septic or malignant processes. Management of hyperlactatemia should target the underlying cause. CONCLUSION: Lactate is a valuable triage and risk stratification tool that can be used to separate patients into higher and lower risk categories. The utility of lactate concentration as a therapeutic target and the measurement of lactate in body fluids shows promise but requires further research.

Treatment of supraventricular tachycardia in a horse.

OBJECTIVE: To describe the treatment of persistent supraventricular tachycardia (SVT) in a young horse in endurance training. CASE SUMMARY: A 6-year-old Arab gelding in endurance training presented for a dysrhythmia and decreased performance. SVT was diagnosed and conversion to a normal sinus rhythm was achieved following administration of a constant rate infusion of amiodarone. However, reversion to SVT occurred shortly after initiation of ridden exercise. A second attempt to convert the dysrhythmia with amiodarone failed, but normal sinus rhythm was achieved with transvenous electrical cardioversion (TVEC). Postmortem examination of the heart revealed extensive fibrous replacement of most of the left atrial myocardium; these changes likely provided the structural substrate for the dysrhythmia. The underlying cause of the fibrosis was not identified. NEW OR UNIQUE INFORMATION PROVIDED: SVT is a form of supraventricular tachyarrhythmia rarely diagnosed in the horse. A recent report has described sudden death of a horse following attempted conversion of SVT with oral flecainide acetate. In the present report, we describe short-term conversion of SVT in a horse using intravenous amiodarone with no significant adverse effects. When the dysrhythmia recurred, the animal was donated for teaching purposes and conversion was achieved with TVEC. Normal sinus rhythm persisted for 2 weeks until the horse was euthanized for postmortem evaluation of the heart. Intravenous amiodarone or TVEC could be considered as treatments for supraventricular tachyarrhyhmias other than atrial fibrillation in the horse.

The Equine Neonatal Central Nervous System: Development and Diseases.

Neonatal encephalopathy is the most common neurologic condition affecting newborn foals and shares similarities with perinatal asphyxia syndrome of human infants. In many cases of neonatal encephalopathy there is no obvious episode of acute or chronic hypoxia and other mechanisms likely play a role in the pathogenesis. Increased concentrations of neuroactive progestagens are found in affected foals; whether these molecules are protective, as has been suggested, or play a role in the pathogenesis is unknown. Neurologic diseases other than neonatal encephalopathy affect foals occasionally and should be considered when evaluating sick foals with clinical signs of neurologic dysfunction.

Blood lactate measurement and interpretation in critically ill equine adults and neonates.

Admission blood lactate concentration is widely used as a prognostic indicator in equine medicine and can be a useful indicator of disease severity but typically fails to completely discriminate survivors from nonsurvivors. Increased admission lactate concentrations in adult horses typically return to normal within 12 to 24 hours. Lactate concentrations in neonatal foals are higher than adult concentrations for the first 24 to 72 hours of life. Serial measures reflecting both the magnitude and duration of hyperlactatemia might enable more accurate prognostication and provide insight into disease pathogenesis and could be a valuable therapeutic guide.

Use of viscoelastic coagulation testing to monitor low molecular weight heparin administration to healthy horses.

OBJECTIVES: To evaluate the utility of thromboelastography (TEG) and Sonoclot analyses to monitor the effects of low molecular weight heparin (LMWH) administration to healthy horses. DESIGN: Randomized crossover study. SETTING: Large animal veterinary teaching hospital. ANIMALS: Six adult mixed breed healthy mares. INTERVENTIONS: LMWH (dalteparin) was administered (50 U/kg subcutaneously) either every 12 or 24 h for 3 consecutive days. Blood samples were collected before LMWH administration and then at selected time points for analysis. Thromboelastography derived R-time (R), K-time (K), angle (ANG), and maximum amplitude (MA), and Sonoclot activated clot time (ACT), clot rate (CR), and platelet function (PF) were measured in whole blood 30 min after sample collection. Change (Δ) and percentage change (%Δ) from baseline of each TEG and Sonoclot variable were subsequently calculated. Anti-factor Xa activity and activated partial thromboplastin time (aPTT) were assayed in harvested plasma. The association between anti-factor Xa activity and TEG and Sonoclot (measured and calculated) variables was assessed by calculating correlation coefficients and multiple regression analysis. The ability of measured and calculated TEG and Sonoclot variables to predict when anti-factor Xa activity fell below suggested thromboprophylactic levels was assessed using receiver operating characteristic curve analysis. MEASUREMENTS AND MAIN RESULTS: The correlation between aPTT and anti-factor Xa activity was weak (r = 0.343). Changes in TEG and Sonoclot variables following LMWH administration were consistent with hypocoagulation. All measured and calculated TEG variables were significantly correlated with anti-factor Xa activity. Sonoclot ACT, ΔACT, CR, ΔCR, and %ΔCR were also significantly correlated with anti-factor Xa activity. TEG ΔR and %ΔR best predicted anti-factor Xa activity below the suggested thromboprophylactic level. CONCLUSIONS: Although correlations were modest, serial measurement of TEG variables may be used to monitor LMWH therapy in horses; however, further research is required in sick horses.

Pharmacodynamics of multi-dose low molecular weight heparin in healthy horses.

OBJECTIVES: To compare the pharmacodynamics of once daily and twice daily administration of low molecular weight heparin (LMWH) administration in horses. STUDY DESIGN: Randomized cross over study. ANIMALS: Adult mixed breed healthy mares (n = 6). METHODS: LMWH (dalteparin) was administered (50 U/kg subcutaneously) either every 12 or 24 hours for 3 consecutive days. Anti-factor Xa activity was measured before and at select time points after LMWH administration. Packed cell volume (PCV), platelet count, partial thromboplastin time (PTT), and anti-thrombin (AT) activity were monitored throughout the study. RESULTS: No changes in PCV, platelet count, or AT activity were detected with either frequency of daily LMWH administration. Values for PTT increased throughout the study but never exceeded the normal reference interval. Anti-factor Xa activity was maintained within or above the suggested thromboprophylactic range (0.1-0.2 U/mL) when LMWH was administered twice daily, but fell below this range ≈ 16 hours after administration when given once daily. For both once and twice daily LMWH administration, the area under the curve was significantly greater after the last dose of LMWH when compared to the first dose. CONCLUSIONS: Administration of LMWH once or twice daily for 3 consecutive days appears to be safe in healthy adult horses. Anti-factor Xa activity was maintained within or above the suggested thromboprophylactic range for 24 hours with twice daily LMWH administration but not with once daily administration.