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In vitro effects of dalteparin on thrombin generation in canine plasma
Author(s) -
GaraBoivin Carolyn,
del 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.12510
Subject(s) - beagle , partial thromboplastin time , thrombin generation , thromboplastin , tissue factor , platelet poor plasma , heparin , thrombin , chemistry , anticoagulant , thrombin time , in vitro , prothrombin time , pharmacology , fissipedia , medicine , platelet , coagulation , biochemistry
Background The calibrated automated thrombogram ( CAT ) is a functional thrombin generation ( TG ) assay that may provide a new approach for monitoring anticoagulant therapy in dogs. The effects of dalteparin on TG variables in dogs are unknown. Objectives Objectives were to establish normal TG variable ranges in dogs and measure the in vitro TG variables in canine pooled platelet‐poor plasma ( PPP ) spiked with different dalteparin concentrations. Methods In the first experiment, plasma samples from 25 adult healthy Beagle dogs and 11 client‐owned healthy dogs of multiple breeds was measured individually for obtaining normal TG values. In the second experiment, separate pools of the remaining PPP from 24 of the 25 previous adult Beagles and from 45 different client‐owned dogs were spiked with dalteparin at 9 concentrations with increasing anti‐factor Xa (anti‐ FX a) activity. Activated partial thromboplastin time, tissue factor‐induced TG , and anti‐ FX a activity were measured for each concentration. Concentration–response relationships were determined with ADAPT v.5, using various nonlinear regression models for stimulatory or inhibitory effects. Results Thrombin generation ranges of client‐owned dogs and Beagles were equivalent only for time‐to‐peak ( P < .05). In vitro dalteparin resulted in a concentration‐dependent decrease in endogenous thrombin potential ( ETP ) in pooled PPP . The estimated dalteparin concentration that produced half the maximal inhibition of baseline ETP ( IC 50 ) was 0.289 U/ mL . Thrombin generation and anti‐ FX a activity were more sensitive than APTT to detect the effects of dalteparin. Conclusions The CAT assay can measure the effects of dalteparin in canine plasma, resulting in significant dose‐dependent decreases in ETP , prompting further in vivo investigation.