The Pharmacodynamics of Enoxaparin in Normal Cats
ACVIM 2008
C.M. Van De Wiele; D.F. Hogan; H.W. Green III; K. Dreher
Purdue University, School of Veterinary Medicine
West Lafayette, IN, USA

Systemic arterial thromboembolic disease is common in the cat most often associated with underlying cardiac disease. Many antithrombotic drugs have been considered in the prevention of thromboembolic disease in cats with the low-molecular weight heparins (LMWH) gaining particular interest over the past decade. The LMWH are fragments of standard heparin which allow continued inhibition of factor Xa with greatly reduced inhibition of factor IIa. For this reason, standard coagulation assays such as aPTT are not altered during LMWH therapy. Pharmacokinetic monitoring of LMWH therapy utilizing anti-Xa assays has been evaluated in veterinary studies with the conclusion that very frequent dosing is required to maintain a therapeutic drug effect. However, it has been established in humans and other animal species that there is no correlation between anti-Xa levels and antithrombotic effect. Additionally, there have been no clinical trials in cats to evaluate a therapeutic drug effect. The purpose of this study was to determine if enoxaparin (Lovenox®) demonstrated an antithrombotic effect in the cat when dosed at the current standard dosing protocol of 1 mg/kg SQ q 12 hrs for 5 consecutive days.

Ten normal, purpose bred cats were used for this venous stasis model and divided into 3 groups: Group A; (n=4) control (untreated), group B; (n=3) 4 hrs post final dose (peak), and group C; (n=3) 12 hours post final dose (trough). The model was created by injecting 5 µCi of 125I-fibrinogen (125I-fib) IV followed by 500 µg/kg tissue thromboplastin IV and subsequent isolation of a segment of the abdominal vena cava. The isolated venous segment was maintained for 20 minutes then removed and the amount of thrombus formed was determined. The extent of thrombus formation was objectively measured by the wet weight of the thrombus normalized to segment length and the percent of 125I-fib accreted within the thrombus compared to the 125I-fib within the entire segment. The degree of thrombus inhibition, as well as anti-Xa levels, were determined for groups B and C.

The median normalized thrombus wet weight and %125I-fib were 0.565 mg/mm and 42.0%, 0.000 mg/mm and 0.0%, and 0.390 mg/mm and 12.2% for group A, group B and group C, respectively. The median percent thrombus inhibition for groups B and C were 100.0% and 72.5%, respectively. Anti-Xa levels were not available at the time of writing so final statistical analyses are pending.

The population numbers are very small in this study and this will most likely negatively impact statistical analysis. However, we conclude that this data suggests that enoxaparin does result in a measurable antithrombotic effect in the normal cat at a dosing interval commonly employed, and at a dosing interval less frequent than suggested from previous studies within the literature.

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Carrie Van De Wiele

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