Lack of heparin absorption (either unfractionated or low-molecular-weight heparin) after oral ingestion necessitates intravenous or subcutaneous administration. Intramuscular injection can produce large hematomas, so it is avoided. In people, more bleeding occurs when unfractionated heparin is administered by repeated intravenous injection compared with a continuous intravenous infusion.¹⁷ But in general, the efficacy and safety of subcutaneous and intravenous heparin are comparable. However, if immediate anticoagulant activity is required and the subcutaneous route is selected, then an initial intravenous bolus should be administered because the anticoagulant effect of heparin is delayed by one to two hours after subcutaneous injection.¹⁷

Unfractionated heparin

Because unfractionated heparin is highly negatively charged, it binds to a number of plasma proteins as well as proteins secreted by platelets and endothelial cells. Some heparin-binding proteins are acute phase reactants and are increased in patients with thromboembolic disease.¹⁷ The variability of plasma concentrations of heparin-binding proteins in patients with thromboembolic disease causes the unpredictable anticoagulant response of unfractionated heparin and, occasionally, heparin resistance, necessitating increased dosing.¹⁷

In a retrospective study, dogs identified with immune-mediated hemolytic anemia were divided into two groups: dogs receiving heparin prophylaxis and those not receiving heparin prophylaxis. Dogs in the heparin-treated group were less likely to survive hospitalization than were those not receiving heparin.³⁰ Since no statistically significant difference was found between the two treatment groups with regard to initial packed cell volume, total bilirubin concentration, or neutrophil count or toxicity, the authors proposed that the difference in survival between the two groups occurred because heparin treatment blocked the binding of endogenous heparan sulfate to antithrombin, thus the anti-inflammatory effects of this endogenous interaction were lost.³⁰

Heparin therapy in cats is commonly initiated after arterial thromboembolism in an effort to stop additional thromboembolic events. Both unfractionated heparin and low-molecular-weight heparin have been recommended for therapy.³¹

Heparin is ineffective in the absence of adequate antithrombin concentrations, so heparin would not be expected to work as a prophylactic anticoagulant in animals with diseases associated with antithrombin deficiency (e.g. protein-losing nephropathy or enteropathy). Reports identify that administering unfractionated heparin results in the decline of antithrombin activity within 24 hours of administration.^32,33 In a retrospective series of critically ill animals in an intensive care unit, antithrombin activity was normal (> 90%) in three of 24 dogs. A significant decrease in antithrombin activity from baseline occurred within 24 hours of heparin and plasma administration. Administering plasma alone failed to increase antithrombin activity in the dogs in this study.³³ Unfractionated heparin administration also decreased antithrombin activity in a group of healthy research dogs with normal antithrombin activity at the outset of the study.³²