Management of INR 6.65 on Warfarin (Jantoven)
For a patient on warfarin with an INR of 6.65 without active bleeding, immediately withhold warfarin and administer oral vitamin K 5 mg, then recheck INR within 24-48 hours. 1
Immediate Actions
Hold all warfarin doses immediately until the INR falls below 3.5, as the bleeding risk becomes clinically unacceptable once INR exceeds 5.0 and increases exponentially at this level. 1, 2
Administer oral vitamin K 5 mg as the primary intervention for INR >6.0 without bleeding. 1 This is the treatment of choice because:
- Oral vitamin K is predictably effective, convenient, and safe compared to parenteral routes 3
- Within 24 hours of oral vitamin K administration, 95% of patients show INR reduction and 85% achieve INR <4.0 3
- The 5 mg dose is appropriate for INR values >6.0, whereas lower doses (1-2.5 mg) are sufficient only for INR 4-10 3, 1
Assessment for Bleeding Risk
Evaluate the patient for high-risk features that warrant closer monitoring or more aggressive management:
- Age >65 years (higher bleeding risk at any INR level) 3, 4
- History of prior bleeding episodes 1
- Mechanical heart valves (thromboembolism risk must be balanced) 3
- Renal failure or alcohol use (associated with increased bleeding) 5
- Concurrent antiplatelet therapy 6
At INR 6.65, the absolute bleeding risk is substantial, with up to 75 adverse events per 100 patient-years. 1 The risk rises steeply and exponentially above INR 6.0. 6
Monitoring Protocol
- Recheck INR within 24-48 hours after vitamin K administration to confirm appropriate reduction 3, 1
- Continue monitoring every 24-48 hours until INR is stable in therapeutic range 1
- More frequent monitoring is indicated until stability is re-established 3
Warfarin Resumption Strategy
When restarting warfarin, reduce the weekly total dose by 10-20% (restart at 80% of previous dose). 1 This is critical to prevent recurrent supratherapeutic INR. 1
- Do not restart warfarin until INR falls below 3.5 1
- The reduced dose accounts for whatever factor caused the initial elevation
- Consider investigating potential causes: drug interactions, dietary changes (vitamin K intake), or compliance issues 3
Important Caveats
Avoid intravenous vitamin K unless life-threatening bleeding is present, as anaphylactic reactions occur in 3 per 100,000 IV doses and can result in cardiac arrest. 1, 4 The subcutaneous route is unpredictable and sometimes delayed in response. 6
Do not use high-dose vitamin K (10 mg) in this non-bleeding scenario, as it may lower INR more than necessary and lead to warfarin resistance for up to a week, making re-anticoagulation difficult. 6, 3
For patients with mechanical heart valves specifically, avoid intravenous vitamin K even at INR >6.0 if not bleeding, as rapid INR reduction increases valve thrombosis risk. 6 These patients should be admitted to hospital, warfarin stopped, and INR allowed to fall gradually. 6
If Active Bleeding Develops
If the patient develops clinically significant bleeding with this INR level:
- Administer vitamin K 5-10 mg by slow intravenous infusion over 30 minutes 6, 4
- For life-threatening bleeding, give 4-factor prothrombin complex concentrate (PCC) 25-50 U/kg plus IV vitamin K 10 mg, targeting INR <1.5 4
- PCC is preferred over fresh frozen plasma due to faster onset (5-15 minutes vs. hours) and no need for blood type matching 3, 4
- Hospital admission with frequent monitoring is required 7
Key Distinction from Lower INR Elevations
The evidence shows conflicting recommendations for INR 5-9: some guidelines suggest vitamin K is optional for INR 5-9 without bleeding 6, 3, while others recommend it for increased bleeding risk. 3 However, at INR 6.65, vitamin K administration is clearly indicated because the bleeding risk becomes substantial above 6.0, and the American Society of Hematology/International Society on Thrombosis and Haemostasis specifically recommends 5 mg oral vitamin K for INR >10. 1 Given that 6.65 approaches this threshold and bleeding risk rises exponentially, the 5 mg dose is appropriate. 6, 1