Anticoagulant effects of low-molecular-weight heparins in healthy cats.
BACKGROUND
Low-molecular-weight heparin (LMWH) has potential benefit in cats at risk for thromboembolic disease. However, LMWH pharmacokinetics has not been characterized in the cat. Drug effect with LMWH may be evaluated with analysis of factor Xa inhibition (anti-Xa) or thromboelastography (TEG).


OBJECTIVE
Administration of LMWH at previously recommended dosages and schedules to healthy cats will result in inhibition of factor Xa and hypocoagulable TEG.


METHODS
In vivo research with heparin was performed in 5 purpose-bred cats.


METHODS
In a prospective study with randomized crossover design, heparin or placebo was administered. Treatments were unfractionated heparin (UFH), 250 IU/kg q6h; dalteparin, 100 IU/kg q12h; enoxaparin, 1 mg/kg q12h; or 0.9% saline, 0.25 mL/kg q6h. Each drug was administered for 5 consecutive days followed by a minimum washout of 14 days. Baseline and post-treatment analyses included anti-Xa, TEG, and prothrombin time/activated partial thromboplastin time.


RESULTS
Mean anti-Xa activity 4 hours after enoxaparin (0.48 U/mL) approached the human therapeutic target (0.5-1.0 U/mL); however, mean trough anti-Xa activity was below detection limits. Mean anti-Xa activity 4 hours after dalteparin was lower, and only 1 cat attained therapeutic target at a single time point. Cats receiving UFH attained target anti-Xa activity and changes in TEG at trough and 4 hours.


CONCLUSIONS
Cats have rapid absorption and elimination kinetics with LMWH therapy. On the basis of pharmacokinetic modeling, cats will require higher dosages and more frequent administration of LMWH to achieve human therapeutic anti-factor Xa activity of 0.5-1 U/mL. Peak anti-Xa activity is predicted at 2 hours after administration of LMWH.
Alwood
Amy J
AJ
Department of Clinical Studies Philadelphia, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA. alwood@avets.us
Downend
Amanda B
AB
Brooks
Marjory B
MB
Slensky
Kimberly A
KA
Fox
Julia A
JA
Simpson
Stephen A
SA
Waddell
Lori S
LS
Baumgardner
James E
JE
Otto
Cynthia M
CM
D000042:Absorption; D000818:Animals; D000925:Anticoagulants / Q000493:pharmacokinetics*; D000990:Antithrombin III / Q000493:pharmacokinetics; D002415:Cats / Q000097:blood / Q000378:metabolism*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D015951:Factor Xa / Q000187:drug effects / Q000378:metabolism; D006495:Heparin, Low-Molecular-Weight / Q000493:pharmacokinetics*; D010314:Partial Thromboplastin Time / Q000662:veterinary; D011446:Prospective Studies; D011517:Prothrombin Time / Q000662:veterinary; D011897:Random Allocation; D013916:Thrombelastography / Q000379:methods / Q000662:veterinary*
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D000990:Antithrombin III; D015951:Factor Xa