In vitro heparinization of canine whole blood with low molecular weight heparin (dalteparin) significantly and dose-dependently prolongs heparinase-modified tissue factor-activated thromboelastography parameters and prothrombinase-induced clotting time.
BACKGROUND
Low-molecular-weight heparin (LMWH) is being used increasingly in veterinary medicine for both treatment and prophylaxis of thromboembolic disease, but no predictable patient-side method exists to monitor its effect.


OBJECTIVE
The aim of this study was to evaluate thromboelastography (TEG) and prothombinase-induced clotting time (PiCT) assays for detecting hemostatic alterations following in vitro heparinization of canine whole blood with dalteparin (Fragmin).


METHODS
Citrated whole-blood samples were collected from 7 clinically healthy dogs. Dalteparin was added at concentrations of 0, 0.156, 0.625, 1.25, and 2.5 U/mL of whole blood. TEG was performed using heparinase cups with tissue factor (TF, 1:50,000) and kaolin as activators. Reaction time (R), clotting time (K), angle (alpha), and maximum amplitude (MA) were recorded. PiCT and anti-FXa activity were measured in plasma.


RESULTS
With TF, increasing concentrations of dalteparin significantly prolonged R and K and significantly decreased alpha and MA. K, alpha, and MA ratios were significantly different from baseline at all dalteparin concentrations and R was significantly different from baseline at concentrations of 0.625, 1.25, and 2.5 U/mL. With kaolin, only R was significantly different from baseline at dalteparin concentrations of 0.625 and 2.5 U/mL. PiCT detected dalteparin concentrations < or = 0.625 U/mL, with a good linear correlation (r(2)=.96, P<.0001).


CONCLUSIONS
These results suggest that TF-activated TEG and PiCT assays should be further evaluated as promising new methods for evaluating the effect of LMWH, using doses in the recommended clinical range and prospective clinical studies.
Jessen
Lisbeth R
LR
Department of Small Animal Clinical Sciences, Faculty of Life Sciences, University of Copenhagen, Denmark. lrmj@life.ku.dk
Wiinberg
Bo
B
Jensen
Asger L
AL
Kjelgaard-Hansen
Mads
M
Jensen
Kate H
KH
Pedersen
Lotte B
LB
Kristensen
Annemarie T
AT
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D017985:Dalteparin / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D019763:Heparin Lyase / Q000378:metabolism*; D007616:Kaolin; D008297:Male; D013916:Thrombelastography / Q000662:veterinary*; D013925:Thromboplastin / Q000378:metabolism*
D000925:Anticoagulants; D007616:Kaolin; D013925:Thromboplastin; D019763:Heparin Lyase; D017985:Dalteparin