A 72-year-old woman presents with ecchymoses and melena. She has been on warfarin for atrial fibrillation and recently started a course of broad-spectrum antibiotics for pneumonia. PT is 45 seconds (INR 5.2), aPTT is mildly prolonged, platelet count and fibrinogen are normal. Which mechanism explains the exaggerated anticoagulation?
- A Antibiotics reduce intestinal vitamin K synthesis by gut flora and displace warfarin from albumin ✓
- B Antibiotics directly inhibit factor Xa, synergizing with warfarin
- C Warfarin-induced immune-mediated destruction of vitamin K-dependent factors
- D Antibiotics activate protein C and protein S, overriding warfarin effect
Correct answer: A. Antibiotics reduce intestinal vitamin K synthesis by gut flora and displace warfarin from albumin
Explanation
Broad-spectrum antibiotics (especially cephalosporins with N-methylthiotetrazole side chain) reduce vitamin K-producing gut flora and can also displace warfarin from albumin binding sites, increasing free drug. Warfarin inhibits vitamin K epoxide reductase. Reduced vitamin K availability amplifies the functional deficiency of factors II, VII, IX, and X. PT prolongs first because factor VII has the shortest half-life (6 hours).
Reference: Katzung Basic and Clinical Pharmacology, 15th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.