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?
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Mar 01, 2007



Hypercoagulability refers to an increased risk of thrombus formation.1 In people, hypercoagulability can be either a congenital or an acquired condition. Congenital hypercoagulability occurs when certain anticoagulant factors such as protein C, protein S, or antithrombin are deficient or because of mutations such as factor V Leiden mutation or prothrombin gene mutation.2,3 Factors causing acquired hypercoagulability include obesity, prolonged recumbency or immobilization, cigarette smoking, contraceptive drugs, pregnancy, malignancy, air travel with prolonged periods of limited activity, tamoxifen therapy, and cardiovascular disease.2,3 Frequently, congenital hypercoagulability in an individual remains undiagnosed until an acquired cause of hypercoagulability occurs concurrently, precipitating a thrombotic event.


Table 1 Diseases or Factors Associated with Thromboembolic Events in Dogs and Cats
Clinical awareness of factors predisposing dogs and cats to hypercoagulable states is increasing. Many conditions have been associated with venous thromboembolic disease in dogs and cats4-7 and arterial thromboembolic disease in cats (Table 1).8-12

With our increased awareness of hypercoagulable states, novel anticoagulant strategies for veterinary use are receiving more attention.13-15 Heparin plays an important role in the prophylaxis of and therapy for venous thromboembolism in people. The traditional therapeutic heparin compound has been unfractionated heparin, but recently a class of heparins known as low-molecular-weight heparins has been developed and FDA-approved for use in people.16 Low-molecular-weight heparins offer therapeutic advantages over unfractionated heparin in people, including less frequent dosing, less intensive therapeutic monitoring of drug effect, and reduced risk of hemorrhage, heparin-induced thrombocytopenia, and paradoxical thrombosis.17 In addition, low-molecular-weight heparins can be administered more easily on an outpatient basis in people than unfractionated heparin can because of once-daily administration.2,17 However, limited information exists in the literature concerning the efficacy and potential therapeutic benefit of low-molecular-weight heparins for treating veterinary patients in the clinical setting.

The goal of this article is to review the physiology of hemostasis, the pathophysiology leading to hypercoagulability, and the mechanism of action, pharmacokinetics, laboratory monitoring, and clinical indications for use of unfractionated heparin and low-molecular-weight heparins.

REVIEW OF HEMOSTASIS

Hemostasis is the process of forming a blood clot to seal an injured vessel and the subsequent removal of this clot when the injury is resolved. The clot prevents ongoing blood loss and also initiates blood vessel repair. Hemostasis can be separated into several phases, which include the formation of a platelet plug (primary hemostasis), stabilization of the platelet plug with cross-linked fibrin (secondary hemostasis), and destruction of the clot by fibrinolysis (tertiary hemostasis).18