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?


Table 2 Commonly Reported Dosage Recommendations for Unfractionated Heparin and Low-Molecular-Weight Heparin Products and Protamine Sulfate
Treatment and monitoring. Several unfractionated heparin dosing schedules exist for prophylaxis of thromboembolism in dogs and cats (Table 2).29,34 Unfractionated heparin is usually administered subcutaneously every six to eight hours.35 In people, treatment is monitored most commonly by APTT. In certain instances, APTT might not provide an accurate evaluation of anticoagulation status because of interfering substances in the patient's blood (e.g. plasma proteins or certain clotting factors) or laboratory variability (reagents and timing).36 Human clinical pathology laboratories can improve the predictability of APTT testing to evaluate heparin drug activity by correlating APTT values with plasma heparin concentrations by using in vitro or ex vivo testing; however, this correlation would have to occur with each new batch of testing supplies for APTT and is not practical in the veterinary setting.

Studies have shown that dogs and cats, like people, have variable responses to unfractionated heparin and require individualized dosing regimens and monitoring to achieve a target drug concentration and avoid bleeding complications.37,38 In addition, APTT reagents are also variable when being used to evaluate canine samples, necessitating monitoring by the same laboratory using the same reagents over time to accurately evaluate therapeutic response.14,39-41 In dogs, the desired APTT target range is 1.5 to 2.5 times greater than the patient baseline.34 Heparin activity can also be assessed by evaluation of active factor X. In this test, heparin binds with antithrombin included in the reagent. Bovine active factor X is also included in the reagent, and the heparin-antithrombin complexes neutralize active factor X. The remaining active factor X is inversely proportional to the heparin content of the sample. The target range for heparin activity as measured by the active factor X assay (also referred to as the anti-activated factor X assay) is 0.3 to 0.6 U/ml for people.36 This assay is not widely available to practicing veterinarians but has been reported in research and academic practice settings. Anti-activated factor X assay is essential as a monitoring tool when low-molecular-weight heparins are administered to animals with renal insufficiency since the drug is renally cleared and renal disease alters reported kinetics.

Low-molecular-weight heparin

In people, low-molecular-weight heparins elicit a more predictable anticoagulant response than does unfractionated heparin because of better bioavailability, a longer half-life, and dose-independent clearance. The half-life of low-molecular-weight heparin is two to four times longer than that of unfractionated heparin. Low-molecular-weight heparins are less likely to bind plasma proteins than is unfractionated heparin, thus increasing bioavailability. Low-molecular-weight heparins are cleared primarily by renal elimination, and their biological half-life is increased in patients with renal disease.17 Administration of low-molecular-weight heparin results in less bleeding than does unfractionated heparin in people. In dogs, the half-life of dalteparin, one type of low-molecular-weight heparin, has been found to be shorter than in people.42 Cats demonstrate more rapid kinetics with low-molecular-weight heparin, necessitating dosing three to four times a day.43

Types and indications. Three different low-molecular-weight heparins have been approved in the United States for use in people: enoxaparin (Lovenox—Sanofi Aventis), dalteparin (Fragmin—Pfizer), and tinzaparin (Innohep—Pharmion).2 Of these, enoxaparin and dalteparin are commonly available and have been used in dogs and cats.31


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