Direct Oral Anticoagulants- DTIs

Question 1

Oral Direct Thrombin Inhibitor (DTI)Dabigatran
MOA

Answer 1

Mechanism of Action:
* Directly inhibits thrombin (both free and fibrin-bound).
* Advantage over heparin: inhibits clot-bound thrombin.

Question 2

Pharmacokinetics

Answer 2

• Oral prodrug, rapidly converted to active form.
  
  • Onset: Peak plasma levels in ~1.5 hours.
  • Half-life: 12–14 hours.
  • Elimination: 80% renal → requires dose adjustment in renal impairment.

Question 3

Indications

Answer 3

1. VTE prophylaxis and treatment.
   
   2. Thromboembolic prophylaxis in nonvalvular atrial fibrillation.
   • Not approved for use in mechanical heart valve patients.

Question 4

Efficacy
RCT evidence

Answer 4

Efficacy (RCT Evidence):
* 150 mg BID superior to warfarin for stroke prevention (AF patients at risk).
* No increase in major bleeding, but:
* Higher GI bleeding risk.
* Some risk of ischemic stroke and intracerebral hemorrhage (ICH).

Question 5

Monitoring challanges

Answer 5

• No reliable clinical test to monitor drug levels.
  
  • Thrombin time (TT): overly sensitive.
  • aPTT: does not correlate well with drug levels.
  • Ecarin clotting time (ECT): accurate but not widely available.

Question 6

Reversal

Answer 6

• Idarucizumab (Praxbind): specific reversal agent.
  
  • Monoclonal antibody to dabigatran.
  • Cost: $3000–$5000 per dose.
  • Used selectively based on:
    Site/severity of bleeding (e.g., ICH vs. minor).
    Time since last dose.
    Renal function.
  • Plasma and PCCs are ineffective or unproven for reversal.