What is the management for a post coronary artery bypass graft (CABG) patient with elevated International Normalized Ratio (INR) and how can blood products be used to correct it?

Management of Elevated INR Post-CABG

For post-CABG patients with elevated INR requiring urgent reversal, immediately administer 4-factor prothrombin complex concentrate (PCC) 25-50 U/kg IV plus vitamin K 5-10 mg by slow intravenous infusion over 30 minutes, targeting INR <1.5. 1, 2

Emergency Reversal Protocol

For life-threatening bleeding or emergency surgery:

• Administer 4-factor PCC as first-line therapy at weight-based dosing: 25 U/kg for INR 2-4,35 U/kg for INR 4-6, or 50 U/kg for INR >6 1, 2
• Simultaneously give vitamin K 5-10 mg IV by slow infusion over 30 minutes 1, 2
• Target INR <1.5 for surgical hemostasis 1, 2
• Recheck INR 15-30 minutes after PCC administration to assess correction 2

PCC is vastly superior to fresh frozen plasma (FFP): PCC achieves INR correction within 5-15 minutes versus hours with FFP, requires no ABO matching, carries minimal fluid overload risk, and has lower infection transmission risk. 2 In the INCH trial, 67% of PCC-treated patients achieved INR ≤1.2 within 3 hours versus only 9% with FFP. 2

Why Vitamin K Must Be Co-Administered

Always give vitamin K with PCC because factor VII in PCC has only a 6-hour half-life—vitamin K is required to stimulate endogenous production of vitamin K-dependent clotting factors for sustained reversal. 1, 2 Without vitamin K, the anticoagulant effect will return as PCC factors are metabolized. 2

Critical dosing caveat: Never exceed 10 mg vitamin K, as higher doses create a prothrombotic state and prevent re-warfarinization for days. 2

Management Based on INR Level and Bleeding Status

INR 5.0-9.0 without active bleeding:

• Withhold warfarin for 1-2 doses and monitor serial INR 2
• Add oral vitamin K 1-2.5 mg only if high bleeding risk factors present (age >65-75 years, prior bleeding history, concomitant antiplatelet drugs, renal failure, alcohol use) 2

INR >10 without bleeding:

• Immediately withhold warfarin and administer oral vitamin K 5 mg 2
• If active bleeding develops, add 4-factor PCC 50 U/kg IV plus vitamin K 5-10 mg IV 2

Major bleeding at any INR:

• Administer 4-factor PCC 25-50 U/kg IV plus vitamin K 5-10 mg IV immediately 1, 2
• Provide local hemostatic measures, volume resuscitation, and packed RBC transfusion as needed 2

Post-CABG Specific Considerations

CABG in fully anticoagulated patients carries increased bleeding risk. 1 For non-emergent CABG, warfarin should be interrupted 5 days preoperatively to allow INR normalization. 1

For emergency CABG with elevated INR: The combination of 4-factor PCC (25 IU/kg) and oral/IV vitamin K is required to obtain fast and sustained restoration of hemostasis at the time of surgery. 1

Interestingly, one observational study of 103 patients undergoing CABG during therapeutic anticoagulation (INR 2.0-3.5) showed no excess major complications compared to controls with INR ≤1.5, though postoperative blood loss was higher (941 vs 754 mL) and more FFP was required. 3 However, this approach is not guideline-recommended and should not be considered standard practice.

Monitoring and Follow-Up

• Recheck INR 30 minutes after PCC administration 2
• Monitor INR serially every 6-8 hours for the first 24-48 hours 2
• Continue monitoring regularly over the next week, as some patients require >1 week to clear warfarin and may need additional vitamin K 2
• Monitor hemoglobin every 4-6 hours until stable if bleeding occurred 2

Thromboprophylaxis Considerations

PCC use increases thrombotic risk during the recovery period—thromboprophylaxis must be considered as early as possible after bleeding control is achieved. 2 Three-factor PCC carries higher thrombotic risk than 4-factor PCC in trauma patients. 2

Resuming anticoagulation: After CABG in patients with established indication for oral anticoagulation, resume anticoagulation as soon as bleeding is controlled, possibly with single antiplatelet therapy, while triple antithrombotic therapy should be avoided. 1

Critical Safety Warnings

Anaphylactic reactions to IV vitamin K occur in 3 per 100,000 doses via a non-IgE mechanism (likely due to polyoxyethylated castor oil solubilizer) and can result in cardiac arrest, severe hypotension, bradycardia/tachycardia, dyspnea, and bronchospasm. 2 Administer by slow infusion over 30 minutes. 1, 2

When FFP Is Acceptable

Use FFP only if PCC is unavailable. 1, 2 If using FFP, typical doses are 200-500 mL of fresh frozen plasma, though this carries risks of fluid overload, transfusion reactions, and delayed INR correction. 4

Recombinant activated factor VII (rFVIIa) is not recommended as first-line therapy due to increased risk of thromboembolic events, especially in elderly patients. 2