What's the best approach for treating a patient with an intracranial hemorrhage who's on anticoagulants like warfarin or aspirin?

Management of Intracranial Hemorrhage in Anticoagulated Patients

Immediately reverse anticoagulation with 4-factor prothrombin complex concentrate (4F-PCC) plus intravenous vitamin K for warfarin-associated ICH, or andexanet alfa for factor Xa inhibitors like apixaban, and discontinue all anticoagulant and antiplatelet agents. 1, 2

Immediate Reversal of Anticoagulation

For Warfarin-Associated ICH

• Administer 4-factor prothrombin complex concentrate (4F-PCC) to rapidly normalize clotting factors, targeting INR <1.5 1, 2
• Give 5-10 mg intravenous vitamin K concurrently, though this takes hours to work 1, 3
• Fresh frozen plasma (FFP) is an alternative but requires larger volumes (200-500 mL) and much longer infusion times, making it inferior to PCC 1, 3
• Protamine sulfate reverses heparin-associated ICH, with dosing dependent on time from heparin cessation 1

The 2015 AHA/ASA guidelines prioritize PCC over FFP because it normalizes INR more rapidly with lower fluid volumes, though both carry thromboembolism risk 1. Warfarin-associated ICH carries approximately 50% mortality and has a prolonged bleeding duration of 12-24 hours, making urgent reversal critical 4, 5.

For Novel Oral Anticoagulants (NOACs)

• Andexanet alfa is the specific reversal agent for factor Xa inhibitors (apixaban, rivaroxaban) 6, 2
• If andexanet alfa is unavailable, use prothrombin complex concentrate or activated PCC 6
• Consider activated charcoal if NOAC ingestion occurred within 2-4 hours 6

NOACs carry lower ICH risk than warfarin (2.6% vs 10.2%) but still substantially higher than no anticoagulation 6, 2, 7.

Discontinuation of Antiplatelet Agents

• Immediately discontinue all antiplatelet agents including aspirin, clopidogrel, prasugrel, ticagrelor, and NSAIDs when ICH is present or suspected 8
• Do NOT transfuse platelets in patients with ICH on antiplatelet agents who are not undergoing neurosurgical procedures—this is potentially harmful (Class 3: Harm) 8
• The PATCH trial demonstrated higher mortality and dependence in patients receiving platelet transfusion without scheduled surgery 8

This applies regardless of hematoma volume or neurological examination 8. Clopidogrel carries particularly high mortality risk (OR 14.7) in traumatic ICH 1.

Imaging and Monitoring Protocol

Initial Assessment

• Obtain immediate non-contrast head CT for any anticoagulated patient with head trauma, regardless of mechanism severity 6, 2
• Anticoagulated patients have 3.9% risk of significant intracranial injury versus 1.5% in non-anticoagulated patients 6, 2
• Even ground-level falls in elderly anticoagulated patients can cause fatal ICH—30% of deaths from ground-level falls involved anticoagulated patients 1

Follow-Up Imaging

• Obtain repeat head CT within 6-24 hours if initial CT shows hemorrhage, as anticoagulated patients have 3-fold increased risk of hemorrhage expansion (26% vs 9%) 1, 6, 2
• Most hematoma expansion occurs within first 6 hours after onset 6
• Immediate repeat CT is mandatory for any neurological deterioration regardless of time since injury 6

Patients with Negative Initial CT

• Neurologically intact patients with negative initial CT can be safely discharged without repeat imaging or admission, as delayed ICH requiring intervention is extremely rare (<1%) 6, 2
• Brief observation (4-6 hours) may be considered for high-risk features: age >80 years, loss of consciousness, amnesia, or GCS <15 6, 2

Resumption of Anticoagulation After ICH

Timing Considerations

• Delay resumption at least 10 weeks for optimal balance of thromboembolism versus rebleeding risk based on survival modeling 1
• The AHA/ASA suggests minimum delay of 1 month after ICH 1
• Risk of rebleeding with early resumption exceeds thromboembolism risk initially, but this reverses over time 1

Risk Stratification

• Lobar ICH location carries highest rebleeding risk and warrants longer delay or alternative therapy 1
• Deep (non-lobar) ICH with strong anticoagulation indication may allow earlier resumption (3-7 days after clinical stability) 8
• Presence of microbleeds on gradient echo MRI significantly increases ICH recurrence risk (OR 12.1) 1
• Older age and ongoing anticoagulation are independent risk factors for recurrence 1

Alternative Strategies

• Antiplatelet monotherapy or left atrial appendage closure may be safer alternatives to warfarin in atrial fibrillation patients after ICH 1
• Antiplatelet agents do not dramatically increase hematoma expansion risk and appear generally safe after ICH 1
• For non-lobar hematomas with strong indications, aspirin may restart 3-7 days after stability 8
• For lobar hematomas, delay antiplatelet agents at least 4-6 weeks 8

Prosthetic Heart Valves

• Early resumption may be necessary due to high embolism risk, typically within 7-10 days 1
• Reversal with FFP or PCC for 7-10 days carries low embolic event rate (5%) with low rebleeding on warfarin resumption (0.8%) 1

Critical Pitfalls to Avoid

• Never delay reversal while waiting for INR results—treat empirically based on medication history 2, 5
• Never use FFP alone without vitamin K, as this provides inadequate reversal 1, 3
• Never transfuse platelets in antiplatelet-associated ICH without planned neurosurgery 8
• Never fail to obtain initial CT in anticoagulated patients after any head trauma, even minor mechanisms 6, 2
• Never unnecessarily admit patients with negative initial CT and normal neurological exam for repeat imaging 6, 2
• Never discontinue anticoagulation without considering indication—thromboembolic risk may outweigh delayed hemorrhage risk in stable patients with negative CT 6, 2
• Never restart anticoagulation before confirming hemorrhage stability with neuroimaging 8
• Never use dual antiplatelet therapy after ICH due to elevated bleeding risk 8

Transport and Consultation

• Transport anticoagulated patients with head injury to facilities capable of rapid CT imaging and anticoagulation reversal 1
• Anticoagulated patients with head injury can undergo rapid decompensation even with initially normal examination 1
• Immediate neurosurgical consultation is required if CT shows hemorrhage 6, 2
• 29% of anticoagulated patients with minor head injuries and GCS 15 had intracranial hemorrhage on imaging 1