Study on biological variation of haemostatic parameters in clinically healthy dogs

Novo Nordisk, København, Capital Region, Denmark
The Veterinary Journal (Impact Factor: 2.17). 08/2007; 174(1):62-8. DOI: 10.1016/j.tvjl.2006.05.003
Source: PubMed

ABSTRACT 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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The inflammatory response to infection can activate the coagulation system via complex interactions. If uncontrolled, this may lead to a consumptive coagulopathy, a major risk factor for a poor clinical outcome. This prospective observational study was conducted to determine whether consumptive coagulopathy in dogs with Babesia rossi infection is related to mortality. Seventy-two client-owned dogs diagnosed with canine babesiosis were included. Diagnosis was confirmed by polymerase chain reaction and reverse line blot and dogs co-infected with Babesia vogeli or Ehrlichia canis were excluded. Blood samples were collected at admission. Coagulation factor-, antithrombin (AT)-, and protein C (PC)-activity, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and D-dimer concentrations were measured. The mortality rate was 18% (13/72 dogs) and the median activities of all the coagulation factors were significantly lower in the non-survivors compared to the survivors. Median PT and aPTT were significantly longer in the non-survivors compared to the survivors. Median AT activity was not significantly different but median PC activity was significantly decreased in the non-survivors. Median D-dimer concentrations were significantly higher in non-survivors compared to survivors. This study showed that dogs that died from B. rossi infection had a more severe consumptive coagulopathy compared to survivors, characterized by procoagulant activation, inhibitor consumption, and increased fibrinolytic activity.
    The Veterinary Journal 10/2012; DOI:10.1016/j.tvjl.2012.09.009 · 2.17 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In research and development studies for human and veterinary medicine, relevant comparators for interpreting clinical pathology results are matched with concurrent control animals. However, reference intervals (RI) provide a comparator database and important aids for interpreting clinical pathology data, especially in laboratory beagle dogs. Furthermore, RI incorporate biologic variation, which includes analytical, intraindividual, and interindividual variation. No studies to date have established RI and studied the effect of biologic variation on hematologic variables in a large group of laboratory dogs. The purpose of this retrospective study was to establish hematologic RI for laboratory beagles according to international recommendations and estimate the effect of biologic variation in routinely measured hematologic analytes by using the databank at a pharmaceutical center. Blood specimens from 340 healthy beagles (age, 9 to 36 mo) were evaluated by using a flow-cytometry-based hematology analyzer. RI and their 90% confidence intervals were established by using a nonparametric method. Effects of sex, age, and weight were investigated. Weight had no effect on any analyte. RBC, Hgb, Hct, MCV, MCH, RBC distribution width, and platelet count increased with age, whereas WBC count decreased. The only clinically relevant effect of sex was observed for platelets, which were lower in male beagles than in female and warranted 2 different RI. The calculated index of individuality showed that population-based RI were appropriate for almost all hematologic analytes, as might be expected for a homogeneous group of laboratory beagles.
    Journal of the American Association for Laboratory Animal Science: JAALAS 01/2015; 54(1):17-24. · 0.73 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Sled dogs performing endurance races have been reported to have a high incidence of gastric erosions or ulcerations and an increased risk of gastro intestinal bleeding leading to death in some cases. In addition, these dogs also become hypothyroid during training and exercise. Canine hypothyroidism has been shown to correlate with decreased von Willebrand factor antigen and potentially increased bleeding tendency. Whether increased gastro intestinal bleeding risk is exacerbated due to changes in the hemostatic balance in unknown. The aim of this study was to investigate the hemostatic balance in sled dogs before and after exercise and in addition evaluate any correlation to thyroid status. Twenty sled dogs have been assessed in untrained and trained condition and immediately after exercise. The first sample was collected in the autumn following a resting period, and subsequently the dogs were exposed to increased intensity of training. After four months the peak of physical condition was reached and a 68 km long sled pulling exercise was performed. Samples were collected before and immediately after the exercise. Evaluated parameters were: plasma thromboelastographic (TEG) R, SP, alpha and MA, activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen, von Willebrand factor (vWf), D-dimer, platelet number, thyroid hormones, hematocrit and C-reactive protein (CRP). Exercise induced an overall hypercoaguable state characterized by significant decreases of TEG R and SP and an increase of alpha, increased concentrations of plasma vWf and decreased aPTT. In addition, a proinflammatory status was seen by a significant increase of serum CRP concentrations. Thyroid status was confirmed to be hypothyroid as training and exercise induced significant decrease of thyroxin (T4), free thyroxin (fT4) and thyroxin stimulating hormone (TSH) concentrations. Fibrinogen decreased significantly and PT increased. The training-induced changes showed correlation between T4, fT4 and aPTT and correlation between TSH and fibrinogen. Exercise-induced changes showed correlation between T4 and PT. Exercise was associated with a hypercoaguable state and an increase of vWf concentration in this group of sled dogs. Decreased thyroid hormone concentrations after training and exercise were confirmed, but were associated with increased and not decreased vWf in this group of sled dogs.
    Acta Veterinaria Scandinavica 02/2014; 56(1):11. DOI:10.1186/1751-0147-56-11 · 1.00 Impact Factor