UHS and UTHSCSA
Department of Pathology
An Educational Publication Sponsored by the Blood Utilization Review Committee
27 May 2005
THE REVERSAL OVERANTICOAGULATION CAUSED BY DIRECT THROMBIN INHIBITORS
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.
• 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)
• 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
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.
1. The information in the DOLS web site is developed for and intended
to help the clinicians of our academic medical community: The University
Health System; The University of Texas Health Science Center at San Antonio;
The South Texas Veterans Healthcare System: Audie Murphy Memorial Veterans
2. If you are from outside of our community and you find that the information is helpful, you are welcome to it, however, we encourage you to consult with their local experts and their health science center libraries for more information.
Last updated on 07 July, 2005 by John D. Olson, M.D.,