Coagulation profiles of healthy Andalusian donkeys are different than those of healthy horses

Background: Coagulation disorders are frequently diagnosed, especially in hospitalized equidae, and result in increased morbidity and mortality. However, hemostatic reference intervals have not been established for donkeys yet. Objectives: To determine whether the most common coagulation parameters used in equine practice are different between healthy donkeys and horses. Animals: Thirty‐eight healthy donkeys and 29 healthy horses. Methods: Blood samples were collected to assess both coagulation and fibrinolytic systems by determination of platelet count, fibrinogen concentration, clotting times (prothrombin time [PT] and activated partial thromboplastin time [aPTT]), fibrin degradation products (FDP) and D‐Dimer concentrations. Results: PT and aPTT in donkeys were significantly (P < .05) shorter than those of horses. In contrast, FDP and D‐Dimer concentrations were significantly (P < .05) higher in donkeys than in horses. Conclusions and Clinical Importance: The coagulation parameters most commonly determined in equine practice are different in donkeys compared with horses. Thus, the use of normal reference ranges reported previously for healthy horses in donkeys might lead to a misdiagnosis of coagulopathy in healthy donkeys, and unnecessary treatments in sick donkeys. This is the first report of normal coagulation profile results in donkeys, and further studies are warranted to elucidate the physiological mechanisms of the differences observed between donkeys and horses.     

Thromboelastography in healthy horses and horses with inflammatory gastrointestinal disorders and suspected coagulopathies

Objectives – To evaluate the use of citrated recalcified (nonactivated) thromboelastography (TEG) in healthy horses and horses with colitis and suspected coagulopathies. Design – Prospective, observational study conducted between October 2007 and June 2009. Setting – Veterinary Teaching Hospital. Animals – Forty‐five healthy adult horses and 12 sick adult horses with colitis and prolonged prothrombin time (PT) or activated partial thromboplastin time (aPTT). Interventions – None. Measurements and Main Results – Whole blood was collected on admission. Coagulation profile (PT, aPTT, platelet count, and fibrinogen concentration) and citrated recalcified whole blood TEG analysis (R‐time [R], K‐time [K], angle [α], maximum amplitude [MA], G value [G], lysis at 60 min [LY60]) were evaluated. Mean values (SD) for TEG parameters in healthy horses were: R=10.4 (3.1) minutes; K=3.5 (1.2) minutes; α=46.3 (11.0)°; MA=55.6 (5.1) mm; G=6,429 (1,341) dyn/cm², and LY60=5.1 (2.4)%. Mean coefficients of variation for intra‐assay/interindividual variability in healthy horses were: R=4.7%/30.7%, K=4.8%/35.3%, α=4.4%/23.8%, MA=1.4%/9.3%, G=3.4%/20.8%, and LY60=13.1%/47.7%, respectively. Horses with colitis and prolonged PT and/or aPTT had longer mean values for R (P<0.001) and K (P<0.001), narrower mean α (P<0.001), decreased mean MA (P=0.001), and smaller mean G (P=0.02); changes consistent with hypocoagulability. Conclusions – Citrated recalcified (nonactivated) TEG demonstrated changes consistent with hypocoagulability in horses with colitis that had preidentified coagulation abnormalities. This technique has high interindividual variability and low intra‐assay variability. TEG may be useful for detecting hypocoagulable states in horses with colitis and suspected coagulopathies.     

Thrombelastography in horses with acute gastrointestinal disease

Background: Coagulopathies in horses with gastrointestinal disease are frequently identified and associated with morbidity and fatality. Objective: Determine if thrombelastography (TEG) identifies abnormalities associated with lesion type, presence of systemic inflammatory response syndrome (SIRS), morbidity, and fatality more consistently than traditional coagulation testing. Animals: One‐hundred and one horses examined for gastrointestinal disease and 20 healthy horses. Methods: TEG, tissue factor (TF)‐TEG, and traditional coagulation panels parameters and percentages of horses with coagulopathies were compared for lesion type, presence of SIRS, complications, and survival. Results: Changes in individual parameters and increased incidence of coagulopathies were associated with fatality (R, P= .007; k‐value [K], P= .004; clot lysis [CL]30, P= .037; CL60, P= .050; angle [Ang], P= .0003; maximum amplitude [MA], P= .006; lysis [Ly]30, P= .042; Ly60, P= .027; CI, P= .0004; ≥ 2 TEG coagulopathies, P= .013; ≥ 3 TEG coagulopathies, P= .038; TF‐R, P= .037; TF‐K, P= .004; TF‐CL30, P < .0001; TF‐CL60, P < .0001; TF‐Ang, P= .005; TF‐Ly30, P= .0002; TF‐Ly60, P < .0001; TF‐CI, P= .043; ≥ 1 TF‐TEG coagulopathies, P= .003; ≥ 2 TF‐TEG coagulopathies, P= .0004; prothrombin tme [PT], P < .0001; activated partial throboplastin time [aPTT], P= .021), inflammatory lesions (MA, P= .013; TF‐CL30, P= .033; TF‐CL60, P= .010; TF‐Ly60, P= .011; ≥ 1 TF‐TEG coagulopathy, P= .036; ≥ 2 TF‐TEG coagulopathy, P= .0007; PT, P= .0005; fibrinogen, P= .019), SIRS (MA, P= .004; TF‐CL30, P= .019; TF‐CL60, P= .013; TF‐Ly30, P= .020; TF‐Ly60, P= .010; PT, P < .0001; aPTT, P= .032; disseminated intravascular coagulation, P= .005), and complications (ileus: aPTT, P= .020; diarrhea: TF‐CL30, P= .040; TF‐Ly30, P= .041; thrombophlebitis: ≥ 1 TF‐TEG coagulopathy, P= .018; laminitis: MA, P= .004; CL60, P= .045; CI, P= .036; TF‐MA, P= .019; TF‐TEG CI, P= .019). Abnormalities in TEG and TF‐TEG parameters were indicative of hypocoagulation and hypofibrinolysis. Conclusions and Clinical Importance: TEG identifies changes in coagulation and fibrinolysis associated with lesion type, SIRS, morbidity, and fatality in horses with gastrointestinal disease.     

Study on biological variation of haemostatic parameters in clinically healthy dogs

Thromboelastography (TEG) may be a valuable supplement to the coagulation assays activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), fibrinogen, antithrombin (AT) and D-Dimer currently used in most clinical pathology laboratories. Allowable imprecision and bias reference limits for analytical tests can be calculated based on measurements of biological variation. No studies to date have examined the effect of biological variation on these haemostasis parameters in the same group of dogs. Plasma samples were collected after a set protocol once weekly for five consecutive weeks from eight healthy dogs (four males and four females) and stored at -80 degrees C until analysis. Randomized duplicate coagulation tests and TEG analyses were performed on all plasma samples within one run. The data were analyzed for outliers and subsequently subjected to nested analysis of variance to obtain the coefficient of analytical, intra-individual and inter-individual variation. From these objective analytical performance standards for imprecision, critical difference, total error and the index of individuality were calculated to assess the utility of conventional population-based reference ranges. All the clotting times (aPTT, PT and TT), fibrinogen, AT and D-Dimer showed a degree of individuality, which may make the use of population-based reference ranges alone an insensitive interpretation criterion, whereas a population-based reference interval seems to be sensitive for interpreting all TEG parameters. Analytical performance standards for imprecision were only met for one of the coagulation assays, whereas all TEG parameters except the alpha angle, alpha achieved this analytical goal.     

Thromboelastography in healthy, sick non-septic and septic neonatal foals

Objectives To evaluate citrated recalcified thromboelastography (TEG) in healthy newborn foals, and to determine intra‐assay, inter‐individual and intra‐individual (at 12 h, 24 h and 7 days after birth) variations. Additionally, to compare TEG variables, haematological values and conventional coagulation profiles from healthy, sick non‐septic, and septic foals. Design Prospective study. Methods The study group comprised 18 healthy, 15 sick non‐septic and 17 septic foals. Two citrated (3.2%; 1 : 9 anticoagulant : blood ratio) blood samples were submitted for haemostatic evaluation using a TEG analyser and conventional coagulation profile. TEG values (R time (R), K time (K), angle (α), maximum amplitude (MA) and G value (G)), complete blood count (CBC) and conventional coagulation profile (prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen concentration (Fib) and antithrombin (AT)) were evaluated. Signalment, presenting complaint, sepsis scores, blood culture results and outcome were taken from the medical records of the sick foals. Results Mean values ± SD for TEG variables in healthy neonatal foals were: R = 11.82 ± 5.35 min, K = 3.06 ± 1.34 min, α= 51.19 ± 12.66 degrees, MA = 55.06 ± 6.67 mm and G = 6361 ± 1700 dyn/cm². Mean coefficients of variation for intra‐assay/inter‐individual/intra‐individual in healthy foals were: R = 3.5/45.2/43.1%; K = 5.3/58.7/28.7%; α= 1.5/24.7/11.9%; MA = 0.3/12.1/6.1%; G = 1.6/26.7/14.7%. Septic foals had significantly greater α, MA and G values than sick non‐septic foals, and significantly greater MA and G than healthy foals, changes that are consistent with hypercoagulability. Weak correlations were detected between TEG variables and haematological or haemostatic values. Conclusions TEG could be used to provide additional information about the haemostatic system in equine neonates.     

Association between hypercoagulability and decreased survival in horses with ischemic or inflammatory gastrointestinal disease

Background: Coagulopathies are common in horses with ischemic or inflammatory gastrointestinal (GI) disturbances. There is indirect evidence suggesting that early stages of these diseases are characterized by hypercoagulability (HC). Hypothesis/Objectives: HC, assessed via thromboelastography (TEG), is common in horses with ischemic or inflammatory GI diseases. The degree of HC is correlated with nonsurvival and thrombotic complications. Animals: Thirty client‐owned horses with ischemic or inflammatory GI disease, 30 client‐owned horses with nonischemic or inflammatory GI disease, and 30 healthy horses (control group). Methods: Prospective, observational clinical study. TEG profiles of 30 horses with ischemic or inflammatory GI disease were obtained on admission and 48 hours after admission, and these were compared with profiles from 30 horses with nonischemic or inflammatory GI disease and 30 healthy controls. Prothrombin time (PT), activated partial thromboplastin time (aPTT), antithrombin activity (AT), and D‐Dimer concentrations were also determined in horses with GI disease. Results: Horses with ischemic or inflammatory GI disease had shorter R times compared with healthy horses (14.8 ± 8.3 versus 22.8 ± 12 minute; P= .011). However, changes were subtle and TEG profiles did not resembled those obtained from animals or humans presumed to be hypercoagulable. Although conventional coagulation testing supported the presence of HC (decreased AT and increased D‐Dimer concentrations), TEG and coagulation abnormalities were rarely found in the same horses and the methods were not statistically related. Conclusions and Clinical Importance: There is evidence of HC in horses with GI disease but techniques for diagnoses require refinement.     

Prolonged activated prothromboplastin time and breed specific variation in haemostatic analytes in healthy adult Bernese Mountain dogs

Coagulation tests are often performed in dogs suspected of haemostatic dysfunction and are interpreted according to validated laboratory reference intervals (RIs). Breed specific RIs for haematological and biochemical analytes have previously been identified in Bernese Mountain dogs, but it remains to be determined if breed specific RIs are necessary for haemostasis tests. Activated prothromboplastin time (aPTT), prothrombin time (PT), selected coagulation factors, D-dimers, fibrinogen, von Willebrand factor and thromboelastography (TEG) were analyzed in healthy Bernese Mountain dogs using the CLSI model. Three analytes (aPTT, TEG [MA] and TEG [G]) were different according to the CLSI model. For aPTT the new RI was markedly different (0-100s). Whereas the new intervals for TEG (MA) and TEG (G) may be due to breed related biological variation, the cause of the prolonged RI for aPTT is at present uncertain.     

Evaluation of a modified thrombelastography assay initiated with recombinant human tissue factor in clinically healthy horses

Background: Thrombelastography (TEG) is used to evaluate the viscoelastic properties of blood during clotting and provides a global assessment of hemostasis and clot lysis. TEG analysis initiated with recombinant human tissue factor (TF) has not been evaluated in clinically healthy horses. Objectives: The purpose of this study was to determine whether TEG results are affected by the time elapsed between sampling and analysis (storage time) of equine blood samples and to establish a preliminary equine reference interval for a modified TEG assay, using recombinant human TF to initiate coagulation. Methods: Citrated blood samples were obtained from 20 clinically healthy adult horses. Thirteen samples were stored for 30, 60, and 120 minutes at room temperature before TEG analysis. Coagulation was initiated by adding 20 μL of CaCl₂ to 330 μL of blood and 10 μL of diluted recombinant TF for a final dilution of 1:3600. Reaction (R) and clotting (K) times, angle (α), and maximum amplitude (MA) were compared between time points. A preliminary reference interval (minimum–maximum values) was determined using data from all 20 horses after 30 minutes of sample storage. Results: There was a significant effect of storage time on R, K, and α but not MA. Reference intervals were: R, 3.65–6.4 minutes; K, 1.8–5.45 minutes; α, 33.4–66.2°; MA, 41.2–64.1 mm; lysis at 30 minutes post‐MA (LY30), <2.75%; and lysis at 60 minutes post‐MA (LY60), 1.55–9.5%. Conclusions: TEG can be performed on equine citrated blood samples using recombinant human TF to activate clot formation. TEG parameters were significantly affected by storage time, suggesting an incomplete inhibition of coagulation in citrated blood.     

Hemostatic abnormalities in dogs with carcinoma: a thromboelastographic characterization of hypercoagulability

Hemostatic abnormalities were investigated in 32 dogs with carcinoma and 19 age-matched healthy dogs. Thromboelastography, hemostasis profile (i.e. prothrombin time [PT], activated partial thromboplastin time [aPTT], fibrinogen concentration), platelet count (PLT), thrombin-antithrombin complexes (TAT), and plasminogen activator inhibitor-1 (PAI-1) activity were evaluated. Dogs with carcinomas had faster thrombus generation (TEG(TG), a mathematic value obtained from the first derivate of the thromboelastographic tracing; 834.8±91.1 vs. 707.8±75.8mm/min; mean±SD), increased fibrinogen concentration (276 vs. 151mg/dL), and PLT (425 vs. 324U×10(9)/L), but had decreased PAI-1 activity (15.7 vs. 26.2IU/mL).The most common hemostatic abnormalities found in carcinoma dogs were hypercoagulability (TEG(TG)>mean+2 SD of healthy dogs) and thrombocytosis (PLT>424×10(9)U/L) in 46% of cases, and hyperfibrinogenemia (fibrinogen >384mg/dL) in 32% of cases. Disseminated intravascular coagulation was uncommon and the extent of disease was not correlated with hypercoagulability. TEG(TG) showed good correlation with fibrinogen (r=0.80) and hyperfibrinogenemia seems to be a main factor of the hypercoagulable state in carcinoma dogs. In conclusion, TEG(TG) is a valid parameter to diagnose hypercoagulability.     

Thrombelastography in dogs admitted to an intensive care unit

Background: Underlying conditions in dogs admitted to an intensive care unit (ICU) can cause hemostatic dysfunction. Thrombelastography (TEG) may be useful in detecting hemostatic alterations as compared with standard coagulation tests. Objectives: The purpose of this study was to compare TEG results and those of standard coagulation tests in identifying hemostatic dysfunction in dogs admitted to an ICU and to investigate associations among the variables measured. Methods: Tissue factor‐activated TEG analysis, d ‐dimer and fibrinogen concentrations, antithrombin (AT) activity, prothrombin time (PT), activated partial thromboplastin time (aPTT), and platelet count were measured using standard techniques on 27 dogs admitted to ICU with a disease known to be associated with hemostatic dysfunction and in 31 clinically healthy control dogs. Results were compared between groups using nonparametric tests and κ analysis; principal component analysis (PCA) and Spearman rank correlation were used to measure associations among variables. Results: Fourteen of 27 ICU dogs had abnormal TEG tracings, which were used to classify the dogs as hypercoagulable (n=11), hypocoagulable (n=3), or normocoagulable (n=13). Hypercoagulable dogs had significantly increased d ‐dimer (P=.03) and fibrinogen (P=.01) concentrations compared with normocoagulable dogs. In ICU dogs, positive associations were identified between maximum amplitude (MA), α‐angle, fibrinogen concentration, and platelet count, and between PT, aPTT, and reaction time (R). Significant correlations were found between MA and fibrinogen (r_s=.76, P<.001) and between reaction time (R) and PT (r_s=.51, P=.003). Conclusions: TEG was useful in detecting hemostatic dysfunction in dogs in an ICU. Positive associations among variables may provide insight as to how overall coagulation status reflects alterations in clot strength and coagulation time. Dogs with TEG tracings indicative of hypercoagulability are likely in procoagulant states. Future studies of the incidence of thrombotic complications in dogs with hypercoagulable TEG tracings are warranted.     

One-stage prothrombin time, activated partial thromboplastin time, thrombin time, fibrin degradation product concentration, and antithrombin activity in healthy adult alpacas

Background: Alpacas are increasingly presented to veterinarians for evaluation and care. Reports of alpaca reference intervals for one‐stage prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), concentration of fibrin degradation products (FDP), and antithrombin (AT) activities are scarce or nonexistent. Objective: The aim of this study was to determine values for blood coagulation times (PT, aPTT, and TT), FDP concentrations, and AT activities in healthy adult alpacas. Methods: Of blood samples collected from 35 clinically healthy adult alpacas via jugular venipuncture and placed into sodium citrate and FDP tubes, 29 samples were assayable for coagulation testing. PT, aPTT, and TT were determined by physical (mechanical) clot detection; AT activity was determined using a thrombin‐specific chromogenic substrate end‐point assay; and FDP concentrations were determined by the slide agglutination method. Results: Median values and ranges (minimum–maximum) were determined for PT (8.7 seconds, 6.6–11.2 seconds), aPTT (17.3 seconds, 11.9–22.5 seconds), TT (10.2 seconds, 5.4–16.0 seconds), and AT activity (123.3%, 104.8–144.2%). The mean concentration of FDP was <8 μg/mL. Conclusion: These values for coagulation times, FDP concentration, and AT activity will provide a useful starting point in the diagnostic evaluation of ill adult alpacas.     

Thromboelastographic changes after gonadectomy in retired racing greyhounds

Twenty-one healthy greyhounds with no history or clinical signs of bleeding disorders, and no abnormalities on physical examination, complete blood count, serum biochemistry profiles (in dogs more than five years of age), and SNAP-4DX test for vector borne diseases underwent routine gonadectomies at the Ohio State University Veterinary Teaching Hospital. Blood samples were collected 24 hours before and after surgery by jugular venepuncture for thromboelastography and haemostasis assays (prothrombin time [PT], activated partial thromboplastin time [aPTT], fibrinogen concentration). The magnitude of the bleeding in each patient was estimated using a bleeding scoring system recently validated in greyhounds. Eight dogs were classified as bleeders and 13 as non-bleeders. Thromboelastograph (TEG) tracings in bleeders were different to that of non-bleeders. Neither sex (odds ratio [OR]: 0.148, P=0.05), haematocrit (OR: 0.907, P=0.39), platelet count (OR: 0.996, P=0.65) or age (OR: 0.949, P=0.83) were predictors of the outcome. None of the variables that evaluated clot kinetics, and fibrinolysis (that is, aPTT OR: 0.781, P=0.51; PT OR: 1.337, P=0.63; TEG(R) OR: 1.269, P=0.06; TEG(K) OR: 1.696, P=0.05; TEG(LY60) OR: 1.028, P=0.81) were able to predict the bleeding episodes. Only the TEG variables that represent the fibrin cross-linking of the clot (TEG(angle) OR: 0.903, P=0.03); and the strength of the clot (TEG(MA) OR: 0.833, P=0.03) were considered predictors of the outcome.     

Thromboelastography: a tool for measuring hypercoagulability, hypocoagulability, and fibrinolysis

Objective: To describe the technique of thromboelastography (TEG) and review the applications of this coagulation test in humans and small animals. Data sources: Data sources included scientific reviews and original research publications. Human data synthesis: TEG in humans has been used for documentation of hypercoagulable and hypocoagulable states and has been shown to be beneficial in patient management. Veterinary data synthesis: Clinical evaluation of TEG in veterinary medicine is limited; however, recent reports have documented evidence of hypercoagulability in dogs with parvovirus and protein‐losing nephropathy. Additionally, many of the research models may be relevant to veterinary patients. Conclusions: TEG provides information about coagulation that is not available through routine coagulation tests. The application of TEG monitoring to veterinary patients shows promise; however, prospective clinical studies are needed.     

Evaluation of latex agglutination kits for detection of fibrin(ogen) degradation products and D-dimer in healthy horses and horses with severe colic

Background: Fibrin(ogen) degradation products (FDPs) and D‐dimer are sensitive indicators of excessive fibrinolysis due to disseminated intravascular coagulation (DIC) in dogs. To the authors' knowledge, latex‐agglutination–based plasma FDP and D‐dimer assays have not been validated for use in horses. Objectives: To determine: 1) sensitivity and specificity of latex‐agglutination serum and plasma FDP and D‐dimer assays for diagnosis of DIC; and 2) their prognostic value in horses with severe colic. Methods: At hospital admission and 24 hours later, blood was collected from 30 healthy horses and 20 horses with severe colic. Horses fulfilling predefined laboratory criteria of DIC were enrolled, and their data were subcategorized by survival for analysis. Platelet counts were determined and coagulation panel testing was performed. Serum and plasma FDP concentrations were measured using separate latex agglutination kits. Plasma D‐dimer concentration was measured using 3 latex agglutination kits and a card immunofiltration test. Test sensitivity and specificity results were determined for healthy horses and those with colic. Median test values were compared between colic survivors and nonsurvivors to evaluate the prognostic usefulness of all tests. Results: Performance characteristics varied among assays and kit suppliers. The FDP assays had low sensitivity (<40%), whereas the most accurate D‐dimer kit had 50% sensitivity and 97% specificity. High D‐dimer concentration was the third most common hemostatic abnormality in horses with colic. Median antithrombin (AT) activity was significantly lower and activated partial thromboplastin time (aPTT) was significantly longer in nonsurvivors than survivors. Conclusions: Commercial latex‐agglutination D‐dimer assays might prove useful as adjunctive tests for the diagnosis of DIC in horses with severe colic; however FDP assays are invalid for this purpose. Low AT activity and prolonged aPTT at admission are associated with a poor prognosis in this patient population.     

Prothrombin time and activated partial thromboplastin time using a point‐of‐care analyser (Abaxis VSpro®) in Bennett's wallabies (Macropus rufogriseus)

There are few reports of coagulation times in marsupial species. Blood samples collected from 14 Bennett's wallabies (Macropus rufogriseus) under anaesthesia during routine health assessments were analysed for prothrombin time (PT) and activated partial thromboplastin time (aPTT) using a point‐of‐care analyser (POC) (Abaxis VSPro®). The wallabies had an aPTT mean of 78.09 s and median of 78.1 s. The PT for all wallabies was greater than 35 s, exceeding the longest time measured on the POC. Although PT was significantly longer, aPTT was similar to the manufacturer's domestic canine reference range.     

FEASIBILITY AND SAFETY OF CONTRAST‐ENHANCED ULTRASOUND IN THE DISTAL LIMB OF SIX HORSES

Vascular alterations play important roles in many orthopedic diseases such as osteoarthritis, tendonitis, and synovitis in both human and equine athletes. Understanding these alterations could enhance diagnosis, prognosis, and treatment. Contrast‐enhanced ultrasound (CEUS) could be a valuable method for evaluation of blood flow and perfusion of these processes in the equine distal limb, however no reports were found describing feasibility or safety of the technique. The goal of this prospective, experimental study was to describe the feasibility and safety of distal limb CEUS in a sample of six horses. For each horse, CEUS of the distal limb was performed after intravenous injections of 5 and 10 ml, as well as intra‐arterial injections of 0.5 and 1 ml contrast medium. Vital parameters were monitored and CEUS images were assessed qualitatively and quantitatively for degree of contrast enhancement. None of the horses had clinically significant changes in their vital parameters after contrast medium injection. One horse had a transient increase in respiratory rate, and several horses had mild increases of systolic blood pressure of short duration after intravenous, but not after intra‐arterial injections. Intra‐arterial injection was possible in all horses and resulted in significantly improved contrast enhancement both quantitatively (P = 0.027) and qualitatively (P = 0.019). Findings from this study indicated that CEUS is a feasible and safe diagnostic test for evaluation of the equine distal limb. Future studies are needed to assess the clinical utility of this test for horses with musculoskeletal diseases.     

Association of admission plasma D-dimer concentration with diagnosis and outcome in horses with colic

Background: Coagulopathies detected in horses with gastrointestinal problems seem to be associated with poor outcome. Plasma D‐Dimer concentration is a sensitive test for assessing coagulopathies. Hypothesis: Plasma D‐Dimer concentration tested on admission is related to diagnosis and outcome in horses with colic. Animals: Four hundred and ninety three horses referred for evaluation of abdominal pain. Methods: Prospective observational clinical study. Horses were grouped according to diagnosis (medical and surgical intestinal obstructions, ischemic disorders with and without intestinal resection, enteritis, peritonitis), outcome (survivors, nonsurvivors), and number of coagulopathies (normal profile, 1 or 2 coagulopathies, subclinical disseminated intravascular coagulation [DIC]). Blood samples were collected on admission and plasma D‐Dimer concentration, clotting times (PT and aPTT), and antithrombin activity were determined. Positive likelihood ratios (LR+) were calculated for evaluation of D‐Dimer cut‐off values, which were later tested in a logistic regression model. Results: Horses with enteritis or peritonitis had significantly (P < .001) higher plasma D‐Dimer concentrations and more severe coagulopathies on admission than horses with other diagnoses. Nonsurvivors also had significantly (P < .001) higher plasma D‐Dimer concentrations at presentation than did survivors, and those horses with subclinical DIC on presentation had an odds ratio (OR) 8.6 (95% confidence interval [CI], 3.3–22.5, P < .001) for nonsurvival. Finally, D‐Dimer concentrations >4,000 ng/mL had a LR+ of 5.9 and an OR 8.8 (95% CI, 4.5–17.1, P < .001) for nonsurvival. Conclusion and Clinical Importance: Plasma D‐Dimer concentration measured on admission can be used to facilitate diagnosis and outcome prediction in horses with colic. A potential cut‐off value for nonsurvival was found at approximately 4,000 ng/mL.     

Tissue factor activated thromboelastography correlates to clinical signs of bleeding in dogs

The ability of a laboratory assay to correlate to clinical phenotype is crucial for the accurate diagnosis and monitoring of haemostasis and is therefore challenging with currently used routine haemostasis assays. Thromboelastography (TEG) is increasingly used to evaluate haemostasis in humans and may well be of value in the workup of dogs suspected of having a haemostatic disorder. This study was undertaken to evaluate prospectively how tissue factor (TF) activated TEG correlated to clinical signs of bleeding in dogs, compared to a routine coagulation profile. A prospective case-control study was performed over a 2 year period from 2004-2006. Eligible dogs were those where the primary clinician requested a coagulation profile to evaluate haemostasis. The dogs were simultaneously evaluated with a TF-activated TEG assay. Twenty-seven dogs, characterised as hypo-coagulable based on the TEG parameter G (<3.2 Kdyn/cm(2)), were included in the study as cases. Size matched control groups of TEG normo- (G=3.2K-7.2 Kdyn/cm(2)) and hyper-coagulable (G>7.2 Kdyn/cm(2)) dogs were selected retrospectively from the eligible dogs. For all dogs, clinical signs of bleeding were noted at time of analysis. There were statistically significant differences between all TEG values of hypo- and normo- and hyper-coagulable dogs. Thromboelastography correctly identified dogs with clinical signs of bleeding with a positive predictive value (PPV) of 89% and a negative predictive value (NPV) of 98% based on G alone. In comparison, the coagulation profile had a PPV between 50-81% and a NPV between 92-93% for detection of bleeding, depending on the observer. In conclusion, a TF-activated TEG G value<3.2K dyn/cm(2) correctly identified dogs with clinical signs of bleeding with very high PPV and NPV, irrespective of observer. The findings strongly suggest that TF- activated TEG may be of value in the workup of dogs suspected of having a haemostatic disorder.     

Evaluation of a point-of-care coagulation analyzer for measurement of prothrombin time, activated partial thromboplastin time, and activated clotting time in dogs

OBJECTIVE: To evaluate a point-of-care coagulation analyzer (PCCA) in dogs with coagulopathies and healthy dogs. ANIMALS: 27 healthy and 32 diseased dogs with and without evidence of bleeding. PROCEDURE: Prothrombin time (PT), activated partial thromboplastin time (aPTT), and activated clotting time (ACT) were determined, using a PCCA and standard methods. RESULTS: Using the PCCA, mean (+/- SD) PT of citrated whole blood (CWB) from healthy dogs was 14.5+/-1.2 seconds, whereas PT of nonanticoagulated whole blood (NAWB) was 10.4+/-0.5 seconds. Activated partial thromboplastin time using CWB was 86.4+/-6.9 seconds, whereas aPTT was 71.2+/-6.7 seconds using NAWB. Reference ranges for PT and aPTT using CWB were 12.2 to 16.8 seconds and 72.5 to 100.3 seconds, respectively. Activated clotting time in NAWB was 71+/-11.8 seconds. Agreement with standard PT and aPTT methods using citrated plasma was good (overall agreement was 93% for PT and 87.5% for aPTT in CWB). Comparing CWB by the PCCA and conventional coagulation methods using citrated plasma, sensitivity and specificity were 85.7 and 95.5% for PT and 100 and 82.9% for aPTT, respectively. Overall agreement between the PCCA using NAWB and the clinical laboratory was 73% for PT and 88% for aPTT. Using NAWB for the PCCA and citrated plasma for conventional methods, sensitivity and specificity was 85.7 and 68.4% for PT and 86.7 and 88.9% for aPTT, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The PCCA detected intrinsic, extrinsic, and common pathway abnormalities in a similar fashion to clinical laboratory tests.     

Thrombelastography in 26 healthy horses with and without activation by recombinant human tissue factor

Objectives – To develop a standardized technique for thrombelastography (TEG) analysis in healthy adult horses, with and without the ex vivo addition of tissue factor (TF) as an activator. To determine reference intervals for TEG parameters in the horse, and to determine if traditional coagulation tests correlate with TEG. Design – Prospective, observational. Setting – Veterinary teaching hospital. Animals – Twenty‐six healthy adult horses. Interventions – None. Measurements and Main Results – Thrombelastography with (TF‐TEG) and without (TEG) the addition of TF performed by 4 operators. Coagulation profiles (prothrombin time, activated partial thromboplastin time, platelet count, fibrinogen, antithrombin, and fibrinogen degradation products) were assessed in a subset of horses. Mean values (SD) for TEG parameters in healthy horses were: reaction time (R)=17.0 minutes (3.0 min), K time (K)=5.8 minutes (2.3 min), clotting rate (Ang)=42° (14°), maximum clot strength (maximum amplitude [MA])=60.3 mm (5.7 mm), CL30=97.0% (2.0%), LY30=0.8% (0.6%), CL60=92% (5.9%), LY60=3.2% (2.5%). Mean values (SD) for TF‐TEG parameters were: R‐TF=6.6 minutes (1.4 min), K‐TF=3.1 minutes (1.0 min), Ang‐TF=50.9° (9°), MA‐TF=62.3 mm (5.1 mm), CL30‐TF=97.8% (1.6%), LY30‐TF=0.6% (0.5%), CL60‐TF=90.8% (4.2%), and LY60‐TF=3.6% (1.9%). The addition of TF decreased R and K and increased Ang. TF‐TEG had a narrower SD for R, K, Ang, CL60 and LY60 compared with TEG. Interoperator differences were reduced by the addition of TF. Regression analysis indicated a positive relationship between MA and fibrinogen concentrations (P=0.02) and R‐TF time and prothrombin time (P=0.03). Conclusion – TF‐TEG using the described protocol may minimize variability in data obtained across institutions or users. However, due to the variability associated with different operators, it is recommended that each laboratory set up individual reference intervals with the personnel who will perform the assay, and that the assay protocols and data obtained are compared on a regular basis.