**10. Thrombin inhibitors**

Thrombin (FIIa) is central to the coagulation process. It usually converts soluble fibrinogen to fibrin, stimulates platelets and activates FV, FVIII, FXI and FXIII. Thrombin inhibitors can work directly on FIIa, or indirectly by preventing activation of FII.

Heparin is long-established as an anticoagulant, which facilitates endogenous antithrombin to decrease activation of FII. The indirect mechanism has limited activity against thrombin that is bound to fibrin or fibrin degradation products (FDPs). In contrast, direct-acting thrombin inhibitors (DTIs) inhibit bound, as well as free, FIIa.

Heparin remains the most widely used drug in this class, but other agents are being investigated that may offer increased efficacy or a more favourable side-effect profile. Thrombin inhibitors may also have administrative advantages over heparin if they can be given orally and if anticoagulation monitoring is unnecessary.
