Unfractionated and low-molecular-weight heparin for hypercoagulability in dogs and cats - Veterinary Medicine
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Unfractionated and low-molecular-weight heparin for hypercoagulability in dogs and cats
A new type of heparin, low-molecular-weight heparin, shows promise as an effective and easier-to-use form of therapy for people prone to thromboembolism. Does the same hold true for dogs and cats?


VETERINARY MEDICINE


Low-molecular-weight heparin has been found to not alter platelet aggregability in dogs.15 In a research model of deep vein thrombosis in dogs, the effects of enoxaparin and dalteparin in thrombus propagation were compared with those of unfractionated heparin. Doses were extrapolated from the human literature for all drugs. This study found that unfractionated heparin was more effective at limiting thrombus growth than either of the low-molecular-weight heparins.44 However, doses used were not based on pharmacokinetic data from dogs, and activated factor X activity was not monitored. In another study, a canine model of aortic thromboembolism was created, and the effects of enoxaparin vs. unfractionated heparin were compared with a control (saline) group. In this model, enoxaparin was found to prevent repetitive platelet-dependent thrombus formation better than unfractionated heparin.45 Regarding literature reports of veterinary clinical use of low-molecular-weight heparin, one case report exists in which low-molecular-weight heparin was administered concurrently with streptokinase in a dog with a thromboembolic event secondary to trauma in which the dog recovered.46

The anticoagulant effects of dosing of dalteparin and enoxaparin have been studied in cats.13,43,47 These studies measured the antithrombotic effect of these drugs by increased detection of inhibition of active factor X, which is a marker for heparin concentration. The studies showed that cats have a shorter duration of heparin activity than dogs or people do, necessitating dosing three to four times a day to achieve similar results. A single retrospective study reports the use of dalteparin in cats for a variety of clinical conditions associated with thromboembolism.48 The most common indication for treatment was evidence of cardiac disease predisposing cats to arterial thromboembolism. The dose averaged 98.8 U/kg, and the administration frequency was once or twice a day. Routine coagulation testing (prothrombin time, APTT) was at the discretion of the attending veterinarians and was infrequently performed. Activated factor X activity was not measured in these cats. Administration of medication was tolerated by the cats' owners. Eight cats of the 57 studied had apparent arterial thromboembolism while receiving dalteparin. The study cats were followed for variable lengths of time, and there was no control population to determine the effectiveness of therapy. Bleeding complications were infrequent; however, dalteparin's role in causing bleeding could not be determined from this report.48

Treatment and monitoring. In people, low-molecular-weight heparin is as effective as unfractionated heparin and can be used as a once-daily therapy. Treatment with low-molecular-weight heparin in people requires minimal or no therapeutic monitoring in most patient populations since the anticoagulant activity is highly correlated with dosage by body weight.17 Although low-molecular-weight heparins are considerably more expensive than unfractionated heparin, less frequent dosing, the ability to perform outpatient therapy, and a reduced need to rely on adjusting treatment with blood monitoring make using low-molecular-weight heparin economically practical in certain settings in people.17

Doses for low-molecular-weight heparin products have been extrapolated from human dosages and research in healthy animals (Table 2). The biggest difference between small animals and people is that the dosing interval for low-molecular-weight heparin is shortened in small animals. Therefore, the once-daily dosing regimens that make these drugs advantageous in people do not appear to exist for veterinary patients. When dalteparin was administered at 100 IU/kg subcutaneously in healthy dogs, the plasma half-life was two hours, and anti-activated factor X activity returned to baseline by 12 hours.49 When repeated doses of dalteparin were administered in dogs, a dose of 150 U/kg every eight hours produced anti-activated factor X assay results of 0.4 to 0.8 U/ml.42 In greyhounds, enoxaparin administered subcutaneously at 0.8 mg/kg every six hours appeared to effectively and consistently maintain therapeutic levels of anti-activated factor X activity.50 In healthy cats administered dalteparin at 180 IU/kg subcutaneously, anti-activated factor X activity peaked 95 minutes after subcutaneous administration. Enoxaparin was administered at a dosage of 1.25 mg/kg subcutaneously, and anti-activated factor X activity peaked 101 minutes after administration and returned toward baseline eight hours after administration.43


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Source: VETERINARY MEDICINE,
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