bivalirudin

Bivalirudin is a synthetic, reversible direct thrombin inhibitor derived from hirudin (originally found in leech saliva). Mechanism: it binds directly to the active catalytic site and exosite-1 of thrombin (factor IIa), inhibiting both circulating and clot-bound thrombin, thereby preventing fibrinogen cleavage to fibrin and inhibiting platelet activation. Unlike heparin, it does not require antithrombin III as a cofactor, and it is not neutralized by platelet factor 4, making it safe in heparin-induced thrombocytopenia (HIT). Pharmacokinetics: short half-life (~25 minutes), administered IV, cleared partially by proteolytic cleavage and renal excretion (dose adjustment needed in renal impairment). Clinical uses: anticoagulation during PCI (alternative to heparin + GP IIb/IIIa inhibitors), and in patients with HIT requiring anticoagulation (as an off-label alternative to argatroban). Monitoring: activated clotting time (ACT) during PCI, aPTT in other settings. Adverse effects: primarily bleeding; no specific reversal agent exists (unlike dabigatran, which has idarucizumab), so management of bleeding is supportive given its short half-life. Compared to heparin, bivalirudin has more predictable pharmacokinetics and lower bleeding risk in some trials (e.g., HORIZONS-AMI), though cost and need for continuous infusion are limitations. Other DTIs include lepirudin, argatroban (preferred in renal failure since hepatically cleared), and oral dabigatran (used for long-term anticoagulation in atrial fibrillation/VTE).