Trombine

Trombine, typically known as thrombin in English, is a serine protease that sits at the heart of the blood coagulation cascade. It is generated in blood plasma as the zymogen prothrombin (factor II) and activated to thrombin by the prothrombinase complex, a combination of factor Xa and factor Va on a phospholipid surface in the presence of calcium ions. The activation of prothrombin is the converging point of the extrinsic and intrinsic pathways, linking tissue factor–VIIa signaling to the formation of active thrombin.

Thrombin has several key substrates and roles. It cleaves fibrinogen to fibrin, which polymerizes to form a clot, and it activates factor XIII to XIIIa, which cross-links fibrin to stabilize the clot. It also amplifies coagulation by proteolytically activating factors V and VIII and by promoting platelet activation and aggregation.

Regulation of thrombin activity is tight. Antithrombin III, with the help of heparin, neutralizes thrombin. Thrombin bound to thrombomodulin changes its substrate preference to activate protein C, which, together with protein S, inactivates factors Va and VIIIa. The tissue factor pathway inhibitor (TFPI) also modulates the initiation of coagulation by the tissue factor pathway.

Clinical relevance: excessive thrombin generation can lead to thrombosis, while deficient thrombin activity can cause bleeding. Anticoagulants such as heparin and direct thrombin inhibitors (e.g., dabigatran) target thrombin activity. Thrombin itself is also used in topical hemostatic preparations during surgery.

Name note: trombine is the term used in some languages for the same enzyme that English sources call thrombin.