Department of Pathology



An Educational Publication Sponsored by the Blood Utilization Review Committee

Tenth Edition
27 May 2005


Rachel Beddard, M.D.

Direct Thrombin Inhibitors (DTI)

Argatroban, Angiomax (bivalirudin), Refludan (lepirudin) and Exanta (ximelagatran)

Route(s) of Administration:
Intravenous injection/infusion for Argatroban and hirudin; oral for Exanta

Mechanism of Action:
All are direct thrombin inhibitors that reversibly bind to the thrombin active site. They do not require the co-factor antithrombin, and exert their anticoagulant effects by inhibiting thrombin-catalyzed or -induced reactions, including fibrin formation; activation of coagulation factors V, VIII, and XIII; activation of protein C; and platelet aggregation.

Usual Indications:
• Prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia (Refludan and Argatroban)
• Anticoagulant in patients with or at risk for heparin-induced thrombocytopenia undergoing percutaneous coronary intervention (Argatroban)
• Anticoagulant in patients with unstable angina undergoing percutaneous transluminal coronary angioplasty and is intended for use with aspirin (Angiomax)
• VTE prophylaxis (Exanta)

Usual Contraindications:
• Use with extreme caution in disease states and other circumstances in which there is an increased danger of hemorrhage
• Patients with overt major bleeding
• Patients with a hypersensitivity to the product

Reversal Agents:
No specific antidote exists for any of the direct thrombin inhibitors. Excessive anticoagulation, with or without bleeding, may be controlled by decreasing the infusion dosage or discontinuing the medication altogether. Anticoagulation parameters generally return to baseline quickly (2-4 hrs for Argatroban; 1 hr for Angiomax; 2.5 hrs for Refludan; and 7 hours for Exanta).

Fresh frozen plasma is ineffective in reversal of DTI effect to achieve hemostasis and should not be used for this purpose.

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Last updated on 07 July, 2005 by John D. Olson, M.D., Ph.D.