Direct Thrombin Inhibitors (Argatroban, Dabigatran, Bivalirudin)

Summary

Direct thrombin inhibitors or DTIs inhibit blood clot formation by blocking the actions of thrombin, also known as factor 2. This medication class includes the drugs dabigatran, argatroban, and the drugs that end in the suffix -rudin, like bivalirudin, lepirudin, and hirudin. DTIs are used to prevent blood clots in patients with atrial fibrillation, deep vein thrombosis, and heparin-induced thrombocytopenia.

Key Points

• Direct Thrombin Inhibitors (DTIs)
  • Drug Names
    • Bivalirudin, lepirudin, hirudin (-rudin ending)
    • Argatroban
    • Dabigatran
  • Mechanism
    • Directly blocks thrombin (Factor IIa) binding
      • Binds to free and clot-associated thrombin
      • Prolongs thrombin time (TT)
      • Prevents formation of clots (secondary hemostasis)
    • Administered orally (dabigatran) or IV (bivalirudin, argatroban)
  • Clinical Use
    • Heparin-induced thrombocytopenia (HIT)
      • Argatroban (parenteral) and lepirudin are primarily used for management of heparin-induced thrombocytopenia.
      • Majorly high-yield (!!!!): you will see a question about this on test day.
    • DVT (Venous thromboembolism/VTE) prophylaxis and atrial fibrillation
      • Dabigatran (oral) is used for DVT prevention and treatment and for stroke prevention in atrial fibrillation.
  • Laboratory Findings
    • No change in PT/PTT
    • Do not require routine lab monitoring
      • Allows dabigatran to be used for long-term oral anticoagulation
  • Reversal
    • Dabigatran: Idarucizumab (monoclonal antibody)
      • This is relatively new - not high-yield yet
    • No reversal agents for argatroban/bivalirudin
      • If life-threatening bleeding, give prothrombin complex concentrate (PCC), which contains factors II (thrombin), IX, and X