Bivalirudin

Bivalirudin works as a direct thrombin inhibitor, binding specifically to both the catalytic site and the anion-binding exosite of thrombin, whether the thrombin is circulating freely or already bound within a clot. Thrombin is a serine proteinase that sits at the center of the clotting process: it cleaves fibrinogen into fibrin monomers and activates Factor XIII to Factor XIIIa, which lets fibrin build a covalently cross-linked framework that stabilizes the thrombus. Thrombin also activates Factors V and VIII, which drives further thrombin generation, and it activates platelets, triggering aggregation and granule release. Bivalirudin's binding to thrombin is reversible, since thrombin gradually cleaves the bivalirudin-Arg3-Pro4 bond, allowing thrombin's active site functions to recover over time.

In laboratory (in vitro) studies, bivalirudin inhibited both soluble (free) and clot-bound thrombin, was not neutralized by substances released during the platelet release reaction, and prolonged the activated partial thromboplastin time (aPTT), thrombin time (TT), and prothrombin time (PT) of normal human plasma in a concentration-dependent manner. The clinical significance of these findings is not yet known.