Argatroban

Argatroban is a direct thrombin inhibitor used as an intravenous anticoagulant in humans. It binds directly to the active site of thrombin, thereby inhibiting both free and clot-bound thrombin without the need for antithrombin. As a synthetic small molecule, it acts rapidly after administration and its effects dissipate as the drug is metabolized.

The primary clinical use of argatroban is in the management of heparin-induced thrombocytopenia (HIT) and known HIT during procedures such as percutaneous coronary intervention (PCI). It provides anticoagulation while avoiding heparin in patients who have or are suspected to have HIT. It may also be used in other settings where direct thrombin inhibition is desirable, subject to clinical judgment and guidelines.

Pharmacokinetics and administration are characterized by intravenous delivery with rapid onset. Argatroban is predominantly cleared by hepatic metabolism and biliary excretion; its clearance is markedly reduced in hepatic impairment. Renal function has little effect on its elimination, so dose adjustments are driven mainly by liver function. The drug is monitored by measuring activated partial thromboplastin time (aPTT), with the target typically set at about 1.5 to 3 times the baseline value, and doses adjusted to reach that range.

When transitioning to other anticoagulants, particularly warfarin, argatroban should be stopped and INR monitored carefully, since argatroban can artificially elevate INR and complicate warfarin dosing. Bleeding is the principal adverse effect; other risks include hypotension and headache. Contraindications include active major bleeding and significant hepatic impairment. Careful patient selection and monitoring are essential to balance thrombosis and bleeding risks.