Monitoring unfractionated heparin therapy in dogs by measuring thrombin generation

The calibrated automated thrombogram (CAT), an assay that permits measurement of thrombin generation in plasma, may be useful in studying hemostatic disorders and anticoagulant therapy in animals.

The aims of the study were to measure thrombin generation in healthy Beagle dogs and to evaluate the potential use of the CAT assay for monitoring therapy with unfractionated heparin (UFH).

Individual platelet-poor plasma samples and a plasma pool from 20 healthy adult Beagles were prepared. Serial UFH plasma dilutions were used to establish an in vitro heparin-sensitivity curve. The pharmacodynamic effects of heparin in vivo were evaluated in Beagles using the CAT assay to measure thrombin generation with tissue factor at a concentration of 5 pM for initiation.

In healthy Beagles, the range of endogenous thrombin potential (ETP) was 238.7-414.0 nM/min (mean ± SD, 340.4 ± 63.1 nM/min). ETP intra-assay and interassay variations were 7.1% and 12.9%, respectively. In vitro, a UFH concentration ≥0.4 U/mL resulted in total inhibition of thrombin generation. In vivo, the maximal effect of UFH on ETP was observed at 170 ± 36 minutes (range, 120-210 minutes) and resulted in a decrease in ETP of 38.5 ± 7.8% (range, 26.5-50.3%). In 210-420 minutes, ETP returned to baseline in 5 dogs.

Our study demonstrates that thrombin generation can be measured in canine plasma and may be useful in assessing the degree of anticoagulation provided by UFH.