Idarucizumab is the specific reversal agent for dabigatran. Its mechanism differs fundamentally from protamine reversal of heparin. What is idarucizumab's mechanism?

• A Idarucizumab reactivates thrombin by competitively displacing dabigatran from its active site
• B Idarucizumab is a humanized monoclonal antibody fragment (Fab) that binds dabigatran with 350 times higher affinity than thrombin, sequestering free and thrombin-bound dabigatran ✓
• C Idarucizumab activates Protein C pathway to restore normal coagulation
• D Idarucizumab provides exogenous fresh frozen plasma factors to overcome dabigatran effect

Explanation

Idarucizumab (Praxbind) is a humanized monoclonal antibody Fab fragment engineered from an anti-dabigatran antibody. It binds the dabigatran molecule itself — both free dabigatran and dabigatran already bound to thrombin — with a KD of approximately 1 femtomolar (350 times higher affinity than dabigatran's affinity for thrombin). This completely sequesters dabigatran, immediately restoring normal thrombin activity. In contrast, andexanet alfa (recombinant modified Factor Xa decoy) reverses rivaroxaban and apixaban by competitively binding and sequestering anti-Xa DOACs. Protamine reverses heparin through electrostatic neutralization (protamine is strongly positively charged, heparin is polyanionic).

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.