What is the management for warfarin (Coumadin) induced bleeding?

Management of Warfarin-Induced Bleeding

For life-threatening or major warfarin-induced bleeding, immediately administer 4-factor prothrombin complex concentrate (PCC) at 25-50 U/kg IV plus vitamin K 5-10 mg by slow intravenous infusion over 30 minutes, targeting INR <1.5. 1

Immediate Reversal Strategy for Active Bleeding

Life-Threatening or Major Bleeding

• Administer 4-factor PCC as first-line therapy at doses based on INR: 25 U/kg for INR 2-4,35 U/kg for INR 4-6, and 50 U/kg for INR >6 1
• Always co-administer vitamin K 5-10 mg IV by slow infusion over 30 minutes because factor VII in PCC has only a 4-6 hour half-life, requiring vitamin K to stimulate endogenous production of clotting factors 1
• PCC achieves INR correction within 5-15 minutes versus hours with fresh frozen plasma (FFP), with no need for ABO matching and minimal risk of fluid overload 1, 2
• Recheck INR 15-60 minutes after PCC administration to assess degree of correction 1

Why PCC Over Fresh Frozen Plasma

• In the landmark INCH trial, 67% of PCC-treated patients achieved INR ≤1.2 within 3 hours versus only 9% of FFP-treated patients 1
• PCC reduced hematoma expansion (18.3% vs 27.1% with FFP) in patients with intracranial hemorrhage 1
• FFP should only be used if PCC is unavailable 2, 3

Management Based on Bleeding Severity

Non-Life-Threatening Bleeding with Elevated INR

• For major bleeding requiring urgent reversal but not immediately life-threatening, administer vitamin K 5-10 mg IV by slow infusion over 30 minutes 1
• Withhold warfarin completely until bleeding is controlled 2
• Transfuse packed red blood cells if hemoglobin continues to drop or patient becomes symptomatic 1
• Monitor hemoglobin every 4-6 hours until stable and bleeding source is controlled 1

Elevated INR Without Active Bleeding

• For INR 5.0-9.0 without bleeding: Withhold 1-2 doses of warfarin and monitor serial INR determinations; add oral vitamin K 1-2.5 mg only if patient has increased bleeding risk factors (advanced age >65 years, history of bleeding, concomitant antiplatelet drugs, renal failure) 1, 2
• For INR >10 without bleeding: Withhold warfarin and administer oral vitamin K 5 mg immediately, with INR recheck within 24 hours 1
• Oral vitamin K achieves INR <4.0 within 24 hours in 85% of patients 1

Critical Vitamin K Dosing Considerations

Dose Selection to Avoid Warfarin Resistance

• Use low-dose vitamin K (<5 mg) in patients requiring early re-anticoagulation to reduce risk of hypercoagulability and warfarin resistance 4, 2
• High-dose vitamin K (≥10 mg) creates a prothrombotic state and prevents re-warfarinization for days 1
• Randomized trials demonstrate optimal doses for INR normalization are between 1-2.5 mg for non-bleeding scenarios 4

Route of Administration

• Oral route is preferred for non-emergency situations due to lower risk of anaphylactoid reactions (3 per 100,000 IV doses) 1
• IV route achieves faster partial correction: 44% reach INR ≤2 within 12 hours versus 14% with oral administration 1
• IV vitamin K must be given by slow infusion over 30 minutes to minimize anaphylactoid reaction risk 1

Resuming Anticoagulation After Bleeding

Timing Considerations

• Do not restart warfarin within the first 3 days due to twofold increased risk of rebleeding 4, 2
• Early resumption of warfarin after day 3 is recommended for patients with high thromboembolic risk (mechanical valves, atrial fibrillation with high CHADS2 score) 4
• Resumption between 7-30 days significantly reduces thromboembolism and death without increasing rebleeding risk 4
• Delay restart if bleeding occurred at critical sites (intracranial, intraspinal, intraocular, pericardial, retroperitoneal) or if bleeding source remains unidentified 1

Bridging Therapy

• Use unfractionated heparin (not LMWH) as bridging therapy after emergency bleeding in high-risk patients because of its shorter half-life (1-2 hours) allowing rapid reversal if rebleeding occurs 4
• Consider thromboprophylaxis as early as possible after bleeding control, as PCC use increases thrombotic risk during recovery 1

Common Pitfalls and Caveats

Do Not Delay Endoscopy for GI Bleeding

• Do not routinely normalize INR before endoscopy for GI bleeding, as retrospective studies show >95% endoscopic hemostasis success rates even at INR 1.5-2.5 4, 2
• A systematic review of over 1800 patients found INR at presentation did not predict recurrent non-variceal upper GI bleeding 4
• Only reverse anticoagulation for serious life-threatening GI bleeding irrespective of INR level 4

Monitoring Requirements

• Monitor INR serially every 6-8 hours for the first 24-48 hours after reversal 1
• Continue monitoring regularly over the next week, as some patients require >1 week to clear warfarin and may need additional vitamin K 1
• If INR remains ≥1.4 within first 24-48 hours after initial PCC, administer FFP 1

Thrombotic Risk Management

• PCC use is associated with increased venous and arterial thrombosis risk during recovery period 1
• Three-factor PCC carries higher thrombotic risk than 4-factor PCC in trauma patients 1
• When restarting warfarin after high-dose vitamin K, may require bridging with heparin until vitamin K effects reverse 1

Dose Reduction Upon Restart

• Reduce weekly warfarin dose by 20-30% when restarting therapy to prevent recurrence of supratherapeutic INR 1
• Investigate and address the cause of INR elevation before resuming therapy 1