title: The monitoring of heparin administration by screening tests in experimental dogs.
abstract: The objective of this study was to investigate the relationship between different screening tests of haemostasis and amidolytic plasma activities of unfractionated (standard) heparin in dogs. Different doses of intravenous (i.v.) [25, 50 or 100 IU Kg(-1)bodyweight (BW)] and subcutaneous (s.c.) heparin (250, 500 and 750 IU kg(-1)) were given to groups each of five clinically healthy adult beagles. Measurements of heparin activity with a factor Xa-dependent chromogenic substrate, activated partial thromboplastin time (APTT) (two different reagents), thrombin time (TT, two different thrombin activities in the reagent: 3 and 6 IU ml(-1)) and the reaction time of the resonance thrombogram (RTG -r) with two different measuring devices were performed at different times. The relationship between ratio values (actual/baseline values) of the coagulation tests and heparin activity was analysed based on regression analysis and correlation coefficient. The greatest alterations were seen for the TT([3 IU ml(-1)])and the RTG -r which were near or exceeded the upper limit of measuring range, if 25 IU kg(-1)BW heparin were given i.v. at heparin plasma levels of 0.54 +/- 0.13 IU ml(-1). These results show, that only APTT and TT measured with high thrombin activity assay appear suitable for guiding high dose heparin therapy in dogs. Averaged alterations of APTT ratio in canine plasma were less than those observed in people for similar plasma heparin levels, indicating that the guideline extrapolated from people for monitoring high dose heparin therapy using APTT may not be valid for use in dogs. After coagulation times had been converted into ratio values, based on regression analysis and Wilcoxon's test, differences of heparin sensitivity were found not only for TT measured with different thrombin activities but also for different APTT reagents (P < 0.001). The correlation between amidylotic antifactor Xa activity and ratio of coagulation times was only moderate and found to be lower for RTG -r (instrument 1: r(s)= 0.711; instrument 2: r(s)= 0.573) than for the other coagulation tests (r(s)= 0.822 to r(s)= 0.890). This indicates a considerable variability of the ratio values of the screening tests at defined heparin plasma activities. These results show, that blood coagulation tests in general are little or unsuitable for heparin antifactor-Xa activity control.
authors.affiliation: Clinic for Small Animals, School of Veterinary Medicine Hannover, Germany. Rmischke@klt.tiho-hannover.de
authors.forename: R
authors.initials: R
authors.lastname: Mischke
authors.forename: C
authors.initials: C
authors.lastname: Jacobs
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D004285:Dogs / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods / Q000662:veterinary; D016903:Drug Monitoring / Q000662:veterinary; D005260:Female; D006493:Heparin / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D010314:Partial Thromboplastin Time / Q000662:veterinary*; D012044:Regression Analysis; D018709:Statistics, Nonparametric; D013918:Thrombin Time / Q000662:veterinary*
chemical_list: D006493:Heparin