Clinical factors influencing the sensitivity to warfarin when restarted after surgery

J Intern Med. 2008 Apr;263(4):412-9. doi: 10.1111/j.1365-2796.2007.01913.x. Epub 2008 Jan 16.


Background and objective: Resumption of oral anticoagulation after surgery may result in a different maintenance dose of warfarin than before the procedure. Knowledge of the clinical determinants of postoperative response could help avoid excessive anticoagulation in sensitive patients or avoid extended delays in achieving a therapeutic level in resistant patients.

Design: Retrospective review.

Subjects: Two hundred warfarin-treated patients who were managed by our clinic for surgery.

Outcome: Two independent adjudicators classified the postoperative response to warfarin as Resistant, Normal or Sensitive, based on previous maintenance dose, international normalized ratio (INR) on the day of resumption, number of days until INR of >1.9 and doses of warfarin given. A third adjudicator resolved disagreements. Clinical data were extracted from the patient records and correlated with the response.

Results: Interobserver agreement for classification of postoperative response was moderate (weighted kappa 0.46) with 37 (18.5%) considered resistant, 135 (67.5%) normal, 27 (13.5%) sensitive and one patient was not classifiable. The main type of surgery was cardiac. In univariable analysis only addition of amiodarone after surgery was associated with a sensitive response (P = 0.04). After adjustment for all other factors with an ordered categorical response, amiodarone remained as the sole independent risk factor (P = 0.02) for a sensitive response, odds ratio 0.41 (95% confidence interval 0.19-0.89) for Normal instead of Sensitive or for Resistant instead of Normal.

Conclusion: Altered sensitivity to warfarin occurs in about one-third of patients after surgery and can be predicted by the introduction of concomitant amiodarone therapy but not by patient factors or the nature of the procedure. Changes in concomitant medications after surgery should alert doctors of the potential for increased sensitivity to warfarin.

MeSH terms

  • Aged
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects*
  • Aryl Hydrocarbon Hydroxylases / metabolism*
  • Cytochrome P-450 CYP2C9
  • Dose-Response Relationship, Drug
  • Drug Resistance
  • Female
  • Heparin / economics
  • Heparin / therapeutic use
  • Humans
  • International Normalized Ratio*
  • Male
  • Polymorphism, Genetic / genetics
  • Postoperative Period
  • Retrospective Studies
  • Sensitivity and Specificity
  • Thromboembolism / prevention & control*
  • Treatment Outcome
  • Vitamin K / antagonists & inhibitors
  • Warfarin / administration & dosage
  • Warfarin / adverse effects*
  • Warfarin / metabolism


  • Anticoagulants
  • Vitamin K
  • Warfarin
  • Heparin
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases