How to manage a patient with a supratherapeutic International Normalized Ratio (INR) due to warfarin (coumarin) in the emergency department?

Management of Supratherapeutic INR from Warfarin in the Emergency Department

For patients with supratherapeutic INR without active bleeding, management depends on the INR level: withhold warfarin alone for INR 4.5-10, add oral vitamin K 1-2.5 mg for INR 5-10 with bleeding risk factors, and give oral vitamin K 5 mg for INR >10; for active major bleeding at any INR, immediately administer 4-factor prothrombin complex concentrate (PCC) 25-50 U/kg IV plus vitamin K 5-10 mg by slow IV infusion over 30 minutes. 1

Risk Stratification by INR Level

INR 4.5-5.0 Without Bleeding

• Withhold warfarin for 1-2 doses and monitor with serial INR determinations without administering vitamin K for most patients 2
• Recheck INR within 24-48 hours to confirm appropriate decline 2
• Resume warfarin at a reduced weekly dose (10-20% lower) once INR returns to therapeutic range 1

INR 5.0-9.0 Without Bleeding

• Omit the next 1-2 doses of warfarin as the primary intervention 1, 2
• Add oral vitamin K 1-2.5 mg only if the patient has increased bleeding risk factors including advanced age (>65 years), history of bleeding, concomitant antiplatelet drugs, renal failure, or alcohol use 1, 2
• For patients without these risk factors, simply withholding warfarin is sufficient 1
• Randomized trials demonstrate no reduction in major bleeding with routine vitamin K use in this range, despite faster INR normalization 1
• Recheck INR within 24-48 hours 2

INR >10 Without Bleeding

• Immediately withhold warfarin and administer oral vitamin K 5 mg 1, 2
• The bleeding risk becomes clinically significant at this level, with one prospective series showing 3.9% major bleeding rate at 90 days 1
• Recheck INR within 24 hours 1
• A retrospective study showed patients given oral vitamin K 2 mg were less likely to have INR >5 by day 3 compared to those who only had warfarin withheld (11.1% vs 46.7%) 3

Management of Active Bleeding

Major Bleeding (Any INR Level)

• Stop warfarin immediately 1
• Administer vitamin K 5-10 mg by slow IV infusion over 30 minutes to avoid anaphylactoid reactions (occurs in 3 per 100,000 doses) 1, 4
• Consider 4-factor PCC 25-50 U/kg IV if bleeding is life-threatening, at critical sites (intracranial, intraspinal, intraocular, pericardial, retroperitoneal, intra-articular, or intramuscular with compartment syndrome), or causing hemodynamic instability 1
• Provide local therapy/manual compression if the bleeding source is accessible 1
• Transfuse packed red blood cells if hemoglobin continues to drop or patient becomes symptomatic 1

Life-Threatening Bleeding

• Immediately administer 4-factor PCC using the following dosing algorithm based on INR: 1
  • INR 2-4: 25 U/kg IV
  • INR 4-6: 35 U/kg IV
  • INR >6: 50 U/kg IV
• Always co-administer vitamin K 10 mg by slow IV infusion because factor VII in PCC has only a 6-hour half-life, requiring vitamin K to stimulate endogenous production of vitamin K-dependent factors 1
• Recheck INR 15-60 minutes after PCC administration to assess degree of correction 1
• PCC achieves INR correction within 5-15 minutes versus hours with fresh frozen plasma (FFP) 1
• In the INCH trial, 67% of PCC-treated patients achieved INR ≤1.2 within 3 hours versus only 9% of FFP-treated patients 1

Vitamin K Administration Routes and Dosing

Oral Route (Preferred for Non-Bleeding)

• Oral vitamin K is the treatment of choice for non-emergency reversal due to predictable effectiveness, convenience, and safety 1, 2
• 95% of patients show INR reduction within 24 hours, with 85% achieving INR <4.0 2
• Oral administration achieves faster partial correction than subcutaneous routes 1

Intravenous Route (Reserved for Bleeding)

• Reserve IV vitamin K only for major bleeding or life-threatening situations 1
• Always administer by slow infusion over 30 minutes to minimize risk of anaphylactoid reactions 1, 4
• IV route achieves faster partial correction: 44% reach INR ≤2 within 12 hours versus only 14% with oral administration 1

Critical Pitfalls and Caveats

Avoid Excessive Vitamin K Dosing

• Do not exceed 10 mg vitamin K for non-bleeding situations, as higher doses create warfarin resistance for up to a week and make re-anticoagulation difficult 1, 2
• High-dose vitamin K (≥10 mg) creates a prothrombotic state and prevents re-warfarinization for days 1

PCC-Specific Considerations

• PCC use increases thrombotic risk during the recovery period; consider thromboprophylaxis as early as possible after bleeding control 1
• Three-factor PCC carries higher thrombotic risk than 4-factor PCC in trauma patients 1
• Fresh frozen plasma should only be used if PCC is unavailable 1, 4
• Recombinant activated factor VII is not recommended as first-line therapy due to increased thromboembolic risk, especially in elderly patients 1, 4

Monitoring Requirements

• Monitor INR serially every 6-8 hours for the first 24-48 hours after intervention 1
• Continue monitoring regularly over the next week, as some patients require >1 week to clear warfarin and may need additional vitamin K 1
• If INR remains ≥1.4 within first 24-48 hours after initial PCC, administer FFP 1

Resuming Anticoagulation

After Bleeding Control

• Do not restart warfarin until: 1
  • Bleeding is completely controlled
  • Source of bleeding is identified and treated
  • Patient is hemodynamically stable
  • Indication for anticoagulation still exists
• Delay restart if: 1
  • Bleeding occurred at a critical site
  • Patient is at high risk of rebleeding
  • Surgical procedures are planned
  • Source of bleeding remains unidentified
• Reduce weekly warfarin dose by 20-30% when restarting to prevent recurrence of supratherapeutic INR 1

Special Populations

• For mechanical valve patients requiring urgent surgery, anticoagulation can be reversed with FFP or IV PCC plus low-dose (1-2 mg) oral vitamin K to avoid difficulty achieving therapeutic INR post-procedure 1
• Elderly patients (>65-75 years) have amplified bleeding risk at any given INR level and require more cautious management 1