Management of Warfarin Based on INR Results
The management of warfarin depends critically on the INR level, presence of bleeding, and patient-specific bleeding risk factors—with most adjustments requiring only dose modification or temporary withholding rather than reversal agents. 1
INR Monitoring Schedule
The frequency of INR monitoring must be adjusted based on therapy phase and stability:
- Initiation phase: Check INR daily after the first dose until therapeutic (2.0-3.0) for 2 consecutive days 2, 3
- Stabilization phase (weeks 2-4): Monitor 2-3 times weekly for 1-2 weeks after achieving therapeutic range 1, 3
- Early maintenance (first month): Check weekly 1, 3
- Stable maintenance: Every 2-4 weeks initially, extending up to 12 weeks for patients with consistently stable INRs 2, 4
- After any dose adjustment: Resume weekly monitoring until 2 consecutive therapeutic values are achieved 4, 3
Dose Adjustment Algorithm for Stable Patients
Use a structured weekly dose adjustment based on INR values: 4, 3
| INR Range | Action | Weekly Dose Adjustment |
|---|---|---|
| <1.5 | Continue warfarin | Increase by 15% [4,3] |
| 1.5-1.9 | Continue warfarin | Increase by 10% [4,3] |
| 2.0-3.0 | Therapeutic range | No change [4,3] |
| 3.1-3.5 | Continue warfarin | Decrease by 10% [1] |
| 3.6-4.9 | Hold 1 dose | Restart at 10% reduction [4,3] |
| 5.0-9.0 (no bleeding) | Hold 1-2 doses | Restart at 15% reduction when INR 2.0-3.0 [1,4] |
| >10 (no bleeding) | Hold warfarin | Give oral vitamin K 2.5-5 mg, recheck in 24 hours [1,4] |
Important caveat: For a single INR slightly out of range (e.g., 3.1) in a previously stable patient, continue the current dose and recheck in 1-2 weeks rather than making immediate adjustments 1, 3
Management of Elevated INR Without Bleeding
INR 5.0-9.0 (No Bleeding)
Withhold warfarin for 1-2 doses and monitor serial INRs—vitamin K is NOT routinely recommended. 1
- Standard approach: Hold warfarin, monitor closely, resume at 15% lower weekly dose when INR returns to 2.0-3.0 1, 4
- Add oral vitamin K 1-2.5 mg ONLY if high bleeding risk factors present: 1
Evidence note: Pooled analysis of 4 RCTs showed vitamin K accelerates INR normalization but does NOT reduce major bleeding (2% vs 0.8%, not significant), supporting selective rather than routine use 1
INR >10 (No Bleeding)
Immediately stop warfarin and administer oral vitamin K 2.5-5 mg; recheck INR within 24 hours. 1, 4
- Expect INR reduction within 24-48 hours 4, 3
- Resume warfarin at 15% lower weekly dose once INR returns to therapeutic range 4
Management of Active Bleeding
Major Bleeding (Any INR)
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, targeting INR <1.5. 1
PCC dosing algorithm based on INR: 1
| INR Range | PCC Dose |
|---|---|
| 2.0-4.0 | 25 U/kg IV [1] |
| 4.0-6.0 | 35 U/kg IV [1] |
| >6.0 | 50 U/kg IV [1] |
Critical points:
- PCC is superior to fresh frozen plasma (FFP): Achieves INR correction in 5-15 minutes vs hours with FFP 1
- Always co-administer vitamin K with PCC: Factor VII in PCC has only 6-hour half-life; vitamin K needed for sustained reversal 1
- FFP only if PCC unavailable: Contains 25-times less clotting factors than PCC 1
- Recheck INR 30 minutes after PCC administration to assess correction 1
Minor Bleeding with Elevated INR
Give vitamin K 5-10 mg IV by slow infusion over 30 minutes. 1
- Consider adding PCC if bleeding at critical sites (intracranial, intraspinal, intraocular, pericardial, retroperitoneal) or hemodynamic instability 1
Special Considerations
Mechanical Heart Valves
Target INR 2.5-3.5 for most mechanical valves; use low-dose vitamin K (1-2 mg oral) if reversal needed to avoid difficulty re-anticoagulating. 2, 1
- Higher INR targets may be needed for caged ball or caged disc valves 5
- Consider bridging anticoagulation if warfarin held for extended periods 1
Elderly Patients (>65 Years)
Elderly patients require lower maintenance doses (typically 2-4 mg daily vs standard 5 mg) and are more sensitive to dose changes. 1
- Reduce weekly dose by 20-30% when resuming after supratherapeutic INR 1
- Advanced age amplifies bleeding risk at any given INR level 1
Poor Oral Intake
Reduced vitamin K absorption from poor intake potentiates warfarin effect—hold warfarin until intake stabilizes and INR is stable for 24-48 hours. 1
Common Pitfalls to Avoid
Do not:
- Make immediate dose changes for single slightly out-of-range INR in previously stable patients 4, 3
- Use routine vitamin K for INR 4.5-10 without bleeding (no reduction in major bleeding demonstrated) 1
- Give high-dose vitamin K (≥10 mg) for non-bleeding situations—causes warfarin resistance for up to one week 1, 3
- Use routine heparin bridging for single subtherapeutic INR (thromboembolism risk only 0.3-0.4%) 4
- Stop heparin/LMWH until INR therapeutic for 2 consecutive days 3
- Administer PCC for asymptomatic INR 4-6 without bleeding 1
Factors Requiring Investigation When INR Unstable
Identify and correct precipitating factors before resuming therapy: 1, 3
- Medication changes: Especially antibiotics (most common cause in elderly), NSAIDs, antifungals 1, 3
- Dietary changes: Fluctuations in vitamin K intake (green vegetables, supplements) 4, 3
- Intercurrent illness: Fever, diarrhea, reduced oral intake 1
- Organ function changes: Liver or renal function alterations 1
- Medication non-adherence 1
Resuming Warfarin After Bleeding
Do not restart warfarin until ALL of the following criteria are met: 1
- Bleeding completely controlled 1
- Source of bleeding identified and treated 1
- Patient hemodynamically stable 1
- Indication for anticoagulation still exists 1
For high thromboembolic risk patients (e.g., mechanical valves), consider early restart after day 3—retrospective data show restarting days 7-30 reduces thromboembolism and mortality without increasing rebleeding, whereas restarting within 7 days doubles rebleeding risk. 1