Fig. 2: The target sites of oral and parenteral anticoagulants on the clotting system.
From: Being precise with anticoagulation to reduce adverse drug reactions: are we there yet?
Vitamin K antagonists (VKAs), notably warfarin, inhibit hepatic vitamin K 2,3 epoxide reductase complex 1 (VKORC1) within the vitamin K cycle. This inhibition decreases active reduced vitamin K, which restricts the post-translational gamma-carboxylation activity of vitamin K-dependent γ-glutamyl carboxylase required by clotting factors II, VII, IX and X to become fully functional. Apixaban, edoxaban and rivaroxaban are direct factor Xa inhibitors, whilst dabigatran inhibits factor IIa (thrombin). A unique pentasaccharide sequence within unfractionated heparin, low molecular weight heparins (LMWHs) and fondaparinux enables high-affinity binding to antithrombin (AT). Heparin chains containing this pentasaccharide sequence and at least 18 saccharide units in length are needed to inactivate factor IIa because bridging to form the ternary heparin/AT/thrombin complex is necessary. Shorter chains containing the pentasaccharide chain can still inactivate Xa and so LMWHs have reduced anti-IIa compared to anti-Xa activity; fondaparinux inhibits Xa but not IIa. Bivalirudin and argatroban are two less frequently used parenterally administered anticoagulants; both are direct thrombin inhibitors. TF tissue factor. Drugs within ovals are orally administered; drugs within rectangles are parenterally administered.
