How to manage a patient with high International Normalized Ratio (INR) and hemodynamic instability due to ongoing intracranial (ICD) bleed?

Management of High INR with Hemodynamically Unstable Intracranial Hemorrhage

For patients with high INR and hemodynamic instability due to ongoing intracranial hemorrhage, immediate reversal of anticoagulation with 4-factor prothrombin complex concentrate (PCC) plus intravenous vitamin K is essential to limit hematoma expansion and improve survival.

Initial Assessment and Stabilization

• Immediately discontinue all anticoagulant medications upon diagnosis or suspicion of intracranial hemorrhage 1
• Assess vital signs and hemodynamic stability every 15 minutes until stabilized 1
• Perform rapid neurological assessment using a validated scale such as CNS score at baseline and repeat at least hourly for the first 24 hours 1
• Evaluate for clinical signs of increased intracranial pressure 1

Anticoagulation Reversal Strategy Based on Anticoagulant Type

For Vitamin K Antagonists (e.g., Warfarin)

• For INR ≥1.4 with intracranial hemorrhage: 1

  • Administer 4-factor PCC immediately (preferred over 3-factor PCC) with dosing based on weight and INR:
    • INR 2 to <4: 25 units/kg
    • INR 4-6: 35 units/kg
    • INR >6: 50 units/kg
  • Administer vitamin K 10 mg IV concurrently with PCC 1, 2
  • If 4-factor PCC is unavailable, use fresh frozen plasma (FFP) at 10-15 mL/kg IV, though this is less effective and takes longer to reverse anticoagulation 1

• Repeat INR testing 15-60 minutes after PCC administration and every 6-8 hours for the next 24-48 hours 1

• If repeat INR remains ≥1.4 within 24-48 hours after initial PCC dosing, consider additional FFP 1

For Direct Thrombin Inhibitors (e.g., Dabigatran)

• Administer idarucizumab 5g IV (in two 2.5g/50mL vials) 1
• If idarucizumab is unavailable, use PCC or activated PCC 1
• Consider activated charcoal (50g) if ingestion occurred within 2 hours 1

For Factor Xa Inhibitors (e.g., Apixaban, Rivaroxaban)

• Administer andexanet alfa to reverse anticoagulant effect 1
• If andexanet alfa is unavailable, use 4-factor PCC 50 U/kg IV or activated PCC 1
• Consider activated charcoal (50g) if ingestion occurred within 2 hours 1

Blood Pressure Management

• Assess blood pressure on initial arrival and every 15 minutes until stabilized 1
• Target systolic blood pressure less than 140 mmHg to reduce risk of hematoma expansion 1
• Use labetalol as first-line treatment for acute blood pressure management if no contraindications exist 1
• Continue close blood pressure monitoring (every 30-60 minutes or more frequently if above target) for at least the first 24-48 hours 1

Neurosurgical Consultation

• Obtain urgent neurosurgical consultation, particularly for patients with: 1
  • Cerebellar hemorrhage with altered level of consciousness or new brainstem symptoms
  • Acute hydrocephalus requiring external ventricular drain placement
  • Consideration for decompressive craniectomy

Special Considerations

For Patients with Mechanical Heart Valves

• The risk assessment must consider both the life-threatening nature of intracranial hemorrhage and the risk of valve thrombosis 1
• For intracranial hemorrhage specifically, the risk to life from continued bleeding outweighs the risk of valve thrombosis, necessitating complete reversal of anticoagulation 1
• Consider resuming anticoagulation after approximately 1 week, as the long-term risk of further intracranial bleeding is lower than that of valve thrombosis 1

For Elderly Patients

• Elderly patients on anticoagulation have higher mortality with traumatic intracranial hemorrhage 1
• Use the same aggressive reversal protocol with 4-factor PCC and vitamin K as in younger patients 1, 3
• Studies show PCC provides faster INR reversal (151.6 ± 84.3 minutes vs. 485.0 ± 321 minutes with FFP alone) and decreased incidence of ICH progression (17.2% vs 44.2%) in geriatric patients 3

Ongoing Management

• Admit to a stroke unit or neuro-intensive care unit once medically stable 1
• Continue neurological assessments hourly for the first 24 hours 1
• Monitor for rebound coagulopathy, especially in patients who received PCC without vitamin K 1
• Consult with stroke specialist, cardiologist, or hematologist regarding timing of anticoagulation resumption, which should be determined on a case-by-case basis 1

Common Pitfalls to Avoid

• Delaying anticoagulation reversal while waiting for laboratory results - initiate reversal based on clinical suspicion and medication history 1, 4
• Using FFP as first-line therapy when PCC is available - PCC provides more rapid INR correction and improved outcomes 1, 4
• Administering vitamin K alone without coagulation factor replacement in active bleeding - this is insufficient for immediate reversal 1, 5
• Failing to repeat INR measurements after initial reversal - rebound coagulopathy can occur, especially without vitamin K administration 1
• Neglecting blood pressure control - aggressive BP management is essential to limit hematoma expansion 1