Direct thrombin inhibitors

Direct thrombin inhibitors

1. Direct thrombin inhibitors Dr Aditya nag

2. INTRODUCTION Class of medication that act as anticoagulants (delaying blood clotting) by directly inhibiting the enzyme thrombin (factor IIa ). Their mechanism of action differs from that of heparin and the synthetic pentasaccharides in that they directly inhibit the active site of thrombin and do not require interaction with antithrombin to produce an anticoagulant effect

3. Types Bivalent Bivalirudin (transient inhibition - is cleaved by thrombin) Lepirudin Desirudin Univalent Argatroban Inogatran Melagatran (and its prodrug ximelagatran ) Dabigatran

4. Uses Bivalent DTIs enjoy limited use in circumstances where heparin would be indicated such as the acute coronary syndrome ("unstable angina"), but cannot be used Argatroban is used for heparin-induced thrombocytopenia Dabigatran is used in prevention of ischemic stroke, as well as intracranial hemorrhage risk and overall mortality for non-valvular atrial fibrillation

5. LEPIRUDIN Prophylaxis or treatment of thrombosis complicating HIT Thrombin affinity (Ki) : Highest Intravenous, subcutaneous Bolus of 0.4 mg kg followed by 0.15 mg kg /h Monitor with aPTT for target ratio 1.5–2.5

6. DESIRUDIN DVT prevention after THR Thrombin affinity (Ki) : Highes t Intravenous, subcutaneous s.c. injection 15 mg twice daily No monitoring necessary

7. Bivalirudin Patients with UA undergoing PTCA; PCI with provisional use of GPI; patients with/at risk of HIT/HITTS undergoing PCI Thrombin Affinity: Intermediate Intravenous Bolus of 0.75 mg /kg followed by 1.75 mg kg /h× 4 h Monitor with ACT after 5 min

8. Argatroban Prophylaxis or treatment of thrombosis complicating HIT Thrombin Affinity: Lowest Intravenous 2 µg /kg /h Monitor with aPTT for target ratio 1.5–3.0

9. dabigatran Oral Selective, reversible DTI VTE prophylaxis after hip- or knee- replacement surgery 150 or 220 mg once daily Monitoring not needed