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Effect of dalteparin administration on thrombin generation kinetics in healthy dogs
Author(s) -
GaraBoivin Carolyn,
Castillo Jérôme R.E.,
Dunn Marilyn E.,
Bédard Christian
Publication year - 2017
Publication title -
veterinary clinical pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 51
eISSN - 1939-165X
pISSN - 0275-6382
DOI - 10.1111/vcp.12489
Subject(s) - medicine , thrombin generation , placebo , pharmacology , heparin , anesthesia , low molecular weight heparin , therapeutic index , platelet , thrombin , drug , pathology , alternative medicine
Background Dalteparin is used to prevent thrombotic complications in dogs. Measurement of anti‐factor Xa (anti‐FXa) activity is currently used for monitoring therapy, but remains a nonfunctional test. The calibrated automated thrombogram ( CAT ) could be a suitable approach for functional monitoring. Objectives We hypothesized that the CAT will detect decreased endogenous thrombin potential ( ETP ) in healthy dogs receiving dalteparin. Methods Twenty‐four healthy adult Beagles were randomly allocated to 4 equal groups. A single subcutaneous ( SC ) dose of 50 U/kg, 100 U/kg, or 150 U/kg of dalteparin was given. Platelet‐poor plasma ( PPP ) was collected over a 24‐hour period and evaluated by thrombin generation (TG) via CAT , anti‐FXa activity, and APTT . Analysis was performed with a repeated‐measures general linear mixed model, and the treated groups were compared to a placebo group. Results Time, dose, and time–dose interaction significantly affected ETP ( P < .0001 for all effects), peak ( P < .0001 for all effects), rate index ( P < .0006 for all effects), and anti‐ FX a activity ( P < .0001 for all effects). No significant time trend was detected in the control group. Dogs receiving the 100 U/kg dalteparin SC injection showed the most homogeneous response of ETP inhibition among treated groups. The % inhibition of ETP from baseline increased nonlinearly as a function of anti‐ FX a activity ( r 2 = .8186). Conclusions The CAT assay can be employed to measure the effects of dalteparin at different doses in healthy dogs, showing sensitivity to time‐ and dose‐dependent changes in ETP and other TG variables. Further investigation of the CAT as a tool for monitoring low molecular weight heparin therapy in dogs is warranted.