Bleeding or High INR on Warfarin or other Anticoagulation

🩸 Key Principle: In any patient with life-threatening bleeding on anticoagulants, stop all anticoagulants immediately and reverse their effect without delay. If unsure, take senior or Haematology advice early — especially if multiple agents or complex comorbidity are involved.

🧭 Assessment

• Identify bleeding severity — major vs non-major (haemodynamic instability, Hb drop ≥2 g/dL, intracranial or retroperitoneal site).
• Assess thrombotic risk:
  • Low risk: AF with low CHA₂DS₂-VASc, provoked DVT, postoperative prophylaxis.
  • High risk: Mechanical heart valve, recurrent unprovoked VTE, AF with prior stroke, antiphospholipid syndrome.
• 📈 Check INR urgently if on warfarin. Investigate causes of over-anticoagulation (drug interactions, antibiotics, liver dysfunction, excess dosing).
• ⚗️ Common interacting drugs: amiodarone, macrolides, fluconazole, metronidazole, and cranberry juice.

💥 Major Bleeding on Warfarin

• Bleeding may be due to warfarin, but if INR is normal, seek alternative causes (ulcer, malignancy, thrombocytopenia, DIC).
• Definition: limb-, sight-, or life-threatening bleeding, or active bleeding with shock (SBP <90 mmHg), oliguria, or Hb fall >2 g/dL.
• Immediate management:
  • Prothrombin Complex Concentrate (PCC, e.g. Beriplex): 25–50 units/kg (round to nearest 500 U, max 5000 U)
  • Vitamin K 5 mg IV
  • Recheck INR and coagulation 15 minutes post PCC.
  • If inadequate correction → consider liver disease, DIC, or underdosing.
  • Recheck at 4–6 hours post-reversal.
• ⚠️ PCC corrects INR rapidly within minutes but has a short duration — vitamin K ensures sustained reversal.

🩹 Non-Major Bleeding on Warfarin

• Give 1–3 mg IV Vitamin K.
• Recheck INR daily (or after 6 hours if bleeding persists).
• IV Vitamin K works within 4–6 hours and is more reliable than oral in active bleeding.

⚖️ No Bleeding – INR 5–8

• Omit warfarin until INR <5 and reduce maintenance dose.
• Consider 1 mg oral Vitamin K if high bleeding risk:
  • Age >70, uncontrolled hypertension, liver/renal disease, recent surgery, concurrent antiplatelets or NSAIDs.
• Recheck INR daily until stable.

⚠️ No Bleeding – INR >8

• Omit warfarin until INR <5 and lower maintenance dose.
• Give 1–5 mg oral Vitamin K (higher dose if very high INR or comorbid risk).
• Monitor INR daily until therapeutic.

🧠 New Neurological Deficit on Warfarin

• Perform an urgent INR and CT head within 1 hour.
• If suspicion of intracranial bleed is high → give PCC + IV Vitamin K immediately while awaiting imaging.
• Do not delay reversal if haemorrhage is clinically probable.

🔪 Warfarin and Surgery

• If surgery can be delayed 6–12 hours → give IV Vitamin K to lower INR.
• If urgent or emergency surgery → give PCC + IV Vitamin K for rapid reversal.
• PCC can induce a transient prothrombotic state — caution in DIC or decompensated liver disease.

📋 BCSH (British Committee for Standards in Haematology) 2011 – Key Recommendations

• All hospitals managing warfarin patients must stock a licensed 4-factor PCC.
• Major bleeding → PCC (25–50 u/kg) + 5 mg IV Vitamin K.
• Do not use recombinant factor VIIa for reversal.
• Fresh frozen plasma (FFP) only if PCC unavailable.
• Non-major bleeding → 1–3 mg IV Vitamin K.
• INR >5 (no bleed) → hold warfarin 1–2 doses and reduce maintenance dose.
• INR >8 (no bleed) → 1–5 mg oral Vitamin K.
• Head injury on warfarin → measure INR urgently, have a low threshold for CT head.
• Suspected intracranial bleed → reverse before imaging if clinically likely.

🧾 Algorithm Summary

💉 Bleeding on Unfractionated Heparin (UFH)

• Stop heparin immediately. Check FBC, platelets, APTT.
• If uncontrolled bleeding → Protamine sulphate (1 mg per 80–100 U UFH given in last 2 h; max rate 5 mg/min).
• Effect is immediate; repeat if bleeding continues (heparin half-life ~1 hour).

💉 Significant Bleeding on LMWH

• Stop LMWH. Check FBC, coagulation screen.
• If within 8 h of dose → give Protamine sulphate 1 mg per 100 anti-Xa units over >5 min.
• If partial response only → further 0.5 mg/100 anti-Xa units.
• If ongoing life-threatening bleed → consider rFVIIa after Haematology discussion.

🧬 Bleeding after Thrombolysis

• Agents: Alteplase, Tenecteplase, Reteplase, Streptokinase, Urokinase → all promote plasmin generation and fibrinolysis.
• Major bleeding (e.g. intracranial haemorrhage) usually occurs within 48 h of administration.

⚕️ Management of Thrombolysis-Related Bleeding

• Stop fibrinolytic and any antithrombotic agents.
• Give FFP 12 mL/kg and IV Tranexamic Acid 1 g every 8 hours.
• If fibrinogen <1.5 g/L → give Cryoprecipitate (10 units raises fibrinogen by ~0.7 g/L) or fibrinogen concentrate.
• Cryoprecipitate also replenishes Factor VIII, vWF, and XIII.

📖 Educational Summary

Reversal of anticoagulation is a time-critical intervention balancing haemostasis and thrombosis risk. PCC rapidly restores vitamin K–dependent clotting factors (II, VII, IX, X) and is now preferred over FFP due to predictable potency and lower volume load. Vitamin K ensures sustained correction by restoring hepatic synthesis capacity. For heparins, the antidote is protamine sulphate; for DOACs, specific reversal agents (idarucizumab for dabigatran, andexanet alfa for factor Xa inhibitors) may be considered if available. In all cases, the cause of over-anticoagulation must be investigated to prevent recurrence — common culprits include antibiotics, dietary change, and poor monitoring.

📚 References

• ANTICOAGULATION-RELATED BLEEDING – NHS Cornwall Guideline Summary
• BCSH Guidelines: Oral Anticoagulation with Warfarin (4th Ed, 2011)
• NICE NG158: Venous Thromboembolic Diseases (2020)
• British Haematology Society: Reversal of Anticoagulation in Bleeding (2022)