Heparin has been used for prophylactic and therapeutic anticoagulation in both human and veterinary medicine for many years. Initially large bolus doses of relatively crude heparin were used, with limited success in controlling thrombosis. This problem lead to the use of lower doses of heparin given several times a day, along with regular monitoring of the patient's APTT and PT. Today, significant clinical improvement in this approach has been achieved with use of low-molecular weight heparin (LMWH). In veterinary medicine, promising results are being obtained with the use of LMWH in both the research and clinical setting.

Unfractionated heparin is the standard 'heparin' that has been used by veterinarians for years. This product is a "soup" of heparin molecules of various sizes, and so has variable biological activity. It contains antithrombin, thrombin and various other proteins in addition to heparin.

Mechanism of action: Interacts with antithrombin III (AT-III) and markedly accelerates the ability of AT-III to inactivate the activated forms of coagulation factors IIa, IXa, and Xa. Of these, factor IIa (thrombin) is most sensitive to inhibition by heparin, and the APTT and PT are prolonged.

Human patients given UFH can develop thrombocytopenia, a phenomenon occasionally seen in dogs and cats.

Because of the unpredictable bioavailability and coagulation system response, the dose of UFH required to achieve a similar degree of anticoagulation is highly variable, and often requires therapy be given every 6 hours.

Low molecular weight heparins such as enoxaparin (Lovenox®) and dalteparin (Fragmin®) contain depolymerized fragments of commercial grade heparin, and have far less variability in molecule size, and far fewer large heparin molecules. Most heparin fragments in LMWH are unable to bind AT-III and factor IIa simultaneously, as this function is size-dependent, and are therefore unable to accelerate the inactivation of thrombin by AT-III. However, LMWH still catalyzes inhibition of factor Xa by AT-III.

Advantages: LMWH has a more consistent pharmacokinetic profile than UFH (due to less variability in factors such as protein binding), and affects the coagulation cascade at only one site (inhibiton of factor Xa), and therefore has a far more predictable bioavailability and effect on coagulation.

Disadvantages: LMWH is far more expensive than UFH. Use of LMWH is also more difficult to monitor because it has much less effect on the APTT and PT. The effects need to be monitored via a factor Xa inhibition assay (presently offered at Cornell's Comparative Coagulation Lab; 607-275-0622).

In research studies, healthy greyhounds were administered enoxaparin, initially starting at a dose of 1 mg/kg SQ q12h (dose extrapolated from use in people). The resulting anticoagulation response was monitored via factor Xa inhibition assay, with the goal of achieving 0.5-2.0 factor Xa inhibition units. Results indicated that the required dose to achieve this degree of anticoagulation was in fact 0.8 mg/kg SQ q6h, a dose very different than the dose that is used in people. A very consistent response was observed, and all dogs were at steady state within 2-3 days, and maintained stable factor Xa inhibition activity. The peak effect was seen at ~2 h post administration, with the trough is reached just prior to the next dosing. None of the treated dogs had prolonged APTT or PT or clinical signs of bleeding.