Direct thrombin inhibitors (DTIs) directly inhibit thrombin and do not require interaction with antithrombin. There are bivalent and univalent DTIs. Bivalent DTIs like bivalirudin and lepirudin are used where heparin is contraindicated, while argatroban is used for heparin-induced thrombocytopenia. Dabigatran is an oral DTI used to prevent stroke from atrial fibrillation. Each DTI has a specific indication, dosing, and monitoring approach depending on its affinity for thrombin.

1. DIRECT
THROMBIN
INHIBITORS

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

5. 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

6. 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

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

8. 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

9. 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

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