What are the dose adjustments for warfarin (coumarin) in patients with a deranged Prothrombin Time (PT) International Normalized Ratio (INR)?

Warfarin Dose Adjustments for Deranged PT/INR

For elevated INR without bleeding, omit warfarin doses and restart at a reduced dose when INR approaches therapeutic range; for INR 5-9, consider oral vitamin K 1-2.5 mg; for INR ≥9, give oral vitamin K 3-5 mg; and for life-threatening bleeding, administer IV vitamin K 10 mg plus prothrombin complex concentrate. 1

Structured Management Algorithm Based on INR Level

INR Above Therapeutic Range but <5.0

• Without bleeding or need for urgent surgery: Reduce the warfarin dose or omit the next dose, then resume at a lower dose when INR approaches the desired therapeutic range 1, 2
• No vitamin K is required at this level unless rapid reversal is needed 1

INR 5.0-9.0

• Without bleeding and no high-risk factors: Omit the next 1-2 doses of warfarin and restart at a lower dose when INR falls into therapeutic range 1
• With bleeding risk factors present: Omit the next dose AND give oral vitamin K₁ 1-2.5 mg to more rapidly lower the INR 1
• This approach reduces INR to <4 in 85% of patients within 24 hours without causing warfarin resistance 1

INR ≥9.0 Without Bleeding

• Give oral vitamin K₁ 3-5 mg, anticipating INR will fall within 24-48 hours 1, 2
• Monitor INR closely and repeat vitamin K as necessary 1
• Larger doses (5 mg) are specifically required when INR is ≥10 1

INR ≥9.0 With Serious Bleeding or Major Overdose (INR ≥20)

• Give vitamin K₁ 10 mg by slow IV infusion (over 30 minutes) 1
• Supplement with fresh frozen plasma or prothrombin complex concentrate according to urgency 1
• May require additional vitamin K doses every 12 hours 1

Life-Threatening Bleeding

• Prothrombin complex concentrate is the treatment of choice, supplemented with vitamin K₁ 10 mg IV 1
• This can be repeated according to INR response 1
• For warfarin-related intracranial hemorrhage, rapid INR normalization is critical to reduce mortality 1

Dose Adjustment Algorithm for Subtherapeutic INR

INR <1.5

• Increase weekly warfarin dose by 15% 2

INR 1.6-1.9

• Increase weekly warfarin dose by 10% 2
• For a single INR ≤0.5 below therapeutic range with previously stable INRs, you may continue current dose and retest within 1-2 weeks 2

INR 2.0-2.9 (Therapeutic for Most Indications)

• No dose change required 2, 3

INR 3.0-3.9

• Decrease weekly warfarin dose by 10% 2

INR 4.0-4.9

• Hold 1 dose, then restart with dose decreased by 10% per week 2

INR ≥5.0

• Hold warfarin until INR is 2-3, then restart with dose decreased by 15% per week 2

Critical Considerations for Vitamin K Administration

Oral vitamin K₁ is the preferred route for non-urgent reversal due to predictable effectiveness and safety advantages over parenteral routes 1, 2

Route-Specific Considerations:

• Oral administration: Predictably effective, convenient, and safe; reduces INR to ≤5 within 24 hours in 95% of patients when given as 1 mg 1
• IV administration: Rapid response but carries risk of anaphylactic reactions; reserve for life-threatening situations 1
• Subcutaneous administration: Unpredictable and sometimes delayed response; not recommended 1

Avoiding Warfarin Resistance:

• Do not use high-dose vitamin K (≥10 mg oral) unless absolutely necessary, as it may cause warfarin resistance for up to one week 1, 2
• Low-dose vitamin K (1-2.5 mg) effectively reduces INR without causing resistance when warfarin is resumed 1

Monitoring Frequency After Dose Adjustment

• Check INR within 24 hours after vitamin K administration for elevated INR 1
• Recheck INR within 1-2 weeks after dose adjustment for subtherapeutic levels 2
• Resume more frequent monitoring (2-4 times weekly) after any dose change until stable 3, 4
• Once stable in therapeutic range, can extend to weekly monitoring for 1 month, then every 1-4 weeks 2, 3

Common Pitfalls to Avoid

• Do not overreact to minor INR deviations with immediate large dose changes when the patient has been previously stable 2
• Avoid loading doses when initiating warfarin, as they increase hemorrhagic complications without providing faster protection 3, 4
• Do not ignore drug interactions: NSAIDs, antibiotics, and other medications significantly affect warfarin response 2
• Assess for bleeding even with "acceptable" INR: Bleeding at INR <3.0 suggests underlying pathology requiring investigation 1, 5
• Consider patient-specific factors: Elderly patients (≥75 years) require approximately 1 mg/day less warfarin than younger individuals and have higher bleeding risk even at therapeutic INR 1

Special Clinical Scenarios

Warfarin-Related Intracranial Hemorrhage:

• Requires immediate aggressive reversal with prothrombin complex concentrate plus IV vitamin K 10 mg 1
• The decision to restart anticoagulation after 7-10 days must balance 5% annual embolic risk against rebleeding risk 1

Urgent Surgery or Procedures:

• Stop warfarin 4-5 days preoperatively to allow INR to return to ≤1.2 1
• Alternatively, give vitamin K₁ 2.5 mg orally 2 days before procedure to shorten the period off warfarin 1
• Consider bridging with heparin in high-risk patients, though not routinely needed for single subtherapeutic INR 2