Pharmacological modulation

The mechanism of action of anticoagulant drugs is based on modulation of the activity of clotting factors involved in coagulation: 

• Inhibit their post-translational modification (e.g. warfarin),
• increase the activity of endogenous coagulation inhibitors (e.g. heparin)
• anticoagulants can directly inhibit the action of clotting factors (e.g. rivaroxaban) [23].

Vitamin K antagonists

Vitamin K antagonists (VKA) function by inhibiting a specific enzyme—vitamin K epoxide reductase— and is found in the pathway that results in active forms of four coagulation factors (II, VII, IX, and X). In blocking this enzyme, VKAs such as warfarin reduce the thrombotic activity of Factors II, VII, IX and X, resulting in a dose-dependent anticoagulant effect. Warfarin has a long history of use as an anticoagulant and until recently was the only oral anticoagulant available [23].

Heparins

Heparins function by indirectly inhibiting anticoagulation by increasing the ability of an endogenous coagulation inhibitor—antithrombin—to inhibit FXa and FIIa. Low-molecular weight heparins (LMWHs) also enhance antithrombin function, but resulting in a predominant inhibition of FXa. Fondaparinux is a synthetic form of heparin that is composed of the antithrombin binding sequence of heparin [23].

Direct Factor Xa and Factor IIa inhibitors

The ‘non-vitamin K antagonist oral anticoagulants’ or sometimes called ‘NOACs’ are direct anticoagulants that target a single clotting enzyme, either FXa or FIIa thereby inhibiting thrombin generation or thrombin activity [24].

Figure: VKAs inhibit the synthesis of FII, FVII, FIX, and FX (green arrows). Heparins inhibit FXa and FIIa indirectly through antithrombin, and fondaparinux indirectly inhibits FXa also via antithrombin. Rivaroxaban and apixaban directly inhibit FXa, and several anticoagulants, including dabigatran, directly inhibit FIIa.