Warfarin Dose Adjustment Based on INR Levels
When to Decrease Warfarin Dose
For INR 5.0-9.0 without bleeding, withhold warfarin for 1-2 doses until INR returns to therapeutic range, then resume at a 10-20% lower weekly dose. 1, 2
Vitamin K is NOT routinely needed for INR 5.0-9.0 without bleeding unless the patient has high bleeding risk factors (age >65-75 years, history of bleeding, concurrent antiplatelet drugs, renal failure, or alcohol use), in which case give oral vitamin K 1-2.5 mg 1, 3
For INR >9.0-10.0 without bleeding, immediately withhold warfarin and administer oral vitamin K 2.5-5 mg, then recheck INR within 24 hours 1, 3
Small incremental adjustments of 5-10% of the weekly dose are preferred for minor INR deviations rather than aggressive dose reductions, which cause INR instability 4
For a single INR reading 0.5 above therapeutic range (e.g., INR 3.5 when target is 2.0-3.0), continuing the current dose without adjustment is reasonable, as randomized trials show no significant difference in outcomes for isolated INRs between 1.5-4.4 4
When to Increase Warfarin Dose
For subtherapeutic INR (below target range), increase the weekly warfarin dose by 5-20% based on how far below target the INR is, then recheck INR in 1-2 weeks. 4, 2
The target INR depends on indication: INR 2.0-3.0 (target 2.5) for most indications including atrial fibrillation, venous thromboembolism, and bileaflet mechanical aortic valves 2, 5
INR 2.5-3.5 (target 3.0) for mechanical mitral valves, tilting disk valves, or caged ball/disk valves 2, 5
Maximum efficacy in atrial fibrillation requires INR >2.0, though some benefit remains at INR 1.5-1.9 6
INR <2.0 carries greater risk of thromboembolism than the bleeding risk associated with INR 2.0-3.0 1, 6
Critical Monitoring Parameters
Check INR daily after initiation until stable in therapeutic range, then extend intervals gradually up to maximum of 4 weeks once stable. 2
After any dose adjustment, recheck INR within 1-2 weeks to confirm stability 4, 1
Additional INR testing is mandatory when other medications are initiated, discontinued, or taken irregularly, as drug interactions are common 2, 5
During amiodarone therapy, monitor INR at least weekly for the first 6 weeks due to potent inhibition of warfarin metabolism through CYP2C9 5
Bleeding Risk Stratification
Bleeding risk increases exponentially with INR >3.0 and becomes clinically unacceptable once INR exceeds 5.0. 6, 1
INR >4.0 provides no additional therapeutic benefit in most patients and is associated with higher bleeding risk 2
Elderly patients (>65 years) have higher bleeding risk at any given INR level 1
For patients >75 years with atrial fibrillation, consider reducing target INR to 2.0-2.5 or even 1.5-2.0 to balance stroke prevention against bleeding risk 6
Management of Elevated INR With Bleeding
For major bleeding at any INR level, 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, 3
PCC achieves INR correction within 5-15 minutes versus hours with fresh frozen plasma 1, 3
Always co-administer vitamin K with PCC because factor VII in PCC has only a 6-hour half-life, requiring vitamin K to stimulate endogenous production of clotting factors 1, 3
For life-threatening bleeding, use PCC 50 U/kg IV (for INR >6) plus vitamin K 10 mg IV, targeting INR <1.5 1, 3
Common Pitfalls to Avoid
Never use loading doses >5 mg, as they increase hemorrhagic complications without offering faster protection against thrombosis. 2
Avoid aggressive dose changes (e.g., reducing from 5 mg to 2 mg) as this causes INR instability and increases time out of therapeutic range 4
Do not exceed 10 mg vitamin K, as higher doses create a prothrombotic state and prevent re-warfarinization for days 1, 3
IV vitamin K carries risk of anaphylactoid reactions (3 per 100,000 doses) and should be given by slow infusion over 30 minutes; oral route is preferred for non-emergency situations 1, 3
Warfarin resistance is rare but should be suspected if large daily doses (>10 mg) are required to maintain therapeutic INR 2