Supratherapeutic INR

Author: Michelle Lin, MD
Updated: 8/10/2012

Overanticoagulation and Supratherapeutic INR from Warfarin

ACCP treatment guidelines for managing supratherapeutic INR (2012, 9th ed)

INR Therapeutic Intervention
≤10 If no bleeding: Hold coumadin. Restart when INR is therapeutic
>10 If no bleeding: Hold coumadin. Give oral vitamin K (2.5 mg)
Major bleed Hold coumadin. Give vitamin K (5-10 mg slow IVP), 4-factor PCC (FFP not of added benefit with 4-factor PCC)

Higher bleeding risk associated with coumadin

  • NSAIDS: non-selective and COX-2 selective
  • Antiplatelet agents: aspirin, clopidogrel
  • Clotrimoxazole
  • Antibiotics (especially fluoroquinolones)


  • Risk of intracranial hemorrhage doubles for every 1-point increase in INR

Causes for supratherapeutic INR >6

Hylek et al. JAMA 1998 study

  • Retrospective case-control study of patients with INR >6
  • Enrolled 93 cases, 196 controls
Risk Factor / Explanation Odds Ratio
Advanced malignancy 16.4

Acetaminophen intake
• 4.5-9.1 g/wk
• > 9.1 g/wk

New medication 8.5
Excess coumadin intake 8.1
Decreased oral intake 3.6
Acute diarrheal illness 3.5
Vitamin K intake 0.7
Alcohol use
(1 drink QOD-2 drinks daily)


  • Hylek EM, Heiman H, Skates SJ, Sheehan MA, Singer DE. Acetaminophen and other risk factors for excessive warfarin anticoagulation. JAMA. 1998 Mar 4;279(9):657-62 [PubMed]
  • Holbrook A, Schulman S, Witt DM, Vandvik PO, Fish J, Kovacs MJ, Svensson PJ, Veenstra DL, Crowther M, Guyatt GH; American College of Chest Physicians.Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.Chest. 2012 Feb;141(2 Suppl):e152S-84S. doi: 10.1378/chest.11-2295. [PubMed]