In an adult with a traumatic intracranial hemorrhage, when can aspirin (acetylsalicylic acid) and clopidogrel (Plavix) be safely restarted?

Restarting Aspirin and Plavix After Traumatic Brain Bleed

For patients with traumatic intracranial hemorrhage who have a compelling indication for antiplatelet therapy, aspirin and clopidogrel can be safely restarted at 7–10 days after the hemorrhage if repeat imaging confirms hematoma stability, though waiting 4 weeks is more conservative for most patients. 1

Immediate Management (First 24–48 Hours)

• Stop all antiplatelet agents immediately upon diagnosis of traumatic intracranial hemorrhage to limit ongoing bleeding and prevent hematoma expansion. 1, 2

• Obtain urgent neurosurgical consultation to evaluate hematoma stability and determine if operative intervention is needed. 2

• Consider platelet transfusion for patients on clopidogrel with substantial bleeding or intracranial hemorrhage, though retrospective data show no clear mortality benefit from platelet transfusion in this setting. 3

• Perform repeat head CT at 12–24 hours to assess for delayed hemorrhage progression, particularly in patients who were on clopidogrel, as they have a 5.1-fold higher risk of progression on repeat imaging compared to controls. 4, 5

Risk Stratification for Resumption Timing

Very High Thromboembolic Risk (Resume at 7–10 Days)

Patients in this category may restart antiplatelet therapy as early as 7–10 days if repeat imaging shows hemorrhage stability: 1, 2

• Mechanical prosthetic heart valves (especially cage-ball valves in mitral position, with annual thromboembolism risk >7%) 1
• CHADS₂ score ≥4 (annual thromboembolism risk >7%) 2
• Recent coronary or carotid stenting within 1–3 months (high acute stent thrombosis risk) 2
• Multiple prior ischemic strokes (documented high recurrent stroke risk) 2

Standard Risk (Resume at 4 Weeks)

For patients with standard cardiovascular indications but not meeting very high-risk criteria: 1

• Wait at least 4 weeks (28 days) before resuming antiplatelet therapy
• Confirm hemorrhage stability on repeat imaging before restarting
• This timing balances the 0.6% risk of delayed traumatic intracranial hemorrhage in warfarin patients (none observed in clopidogrel patients) against thrombotic risk 5

Contraindications to Resumption

Do not restart antiplatelet therapy in patients with: 1, 2

• Lobar hemorrhage location (15% annual recurrence risk, likely cerebral amyloid angiopathy)
• Multiple microbleeds on MRI (very high rebleeding risk)
• Cerebral amyloid angiopathy (extremely high recurrence risk)
• Ongoing hemorrhage expansion on repeat imaging

Agent Selection and Dosing

Monotherapy (Preferred)

• Aspirin 75–100 mg once daily as first-line option 1, 2
• Clopidogrel 75 mg once daily as alternative (slightly lower GI bleeding risk) 2
• Use maintenance dosing only—no loading dose is required when restarting after traumatic brain bleed 6

Dual Antiplatelet Therapy

• Avoid dual antiplatelet therapy (aspirin + clopidogrel) after traumatic intracranial hemorrhage due to significantly increased bleeding risk without proven benefit in this population 2
• Exception: If patient has a drug-eluting stent placed within 1–3 months, continue P2Y12 inhibitor (clopidogrel preferred) and consider stopping aspirin to reduce bleeding risk 2

Evidence Supporting Early Resumption

• The RESTART trial (2019) demonstrated that resuming antiplatelet therapy after intracranial hemorrhage did not increase recurrent hemorrhage risk (adjusted HR 0.51,95% CI 0.25–1.03), and may even reduce it. 2, 7

• A 2023 retrospective cohort study of 1,584 patients showed early antiplatelet resumption (≤30 days) had similar 1-year recurrent intracranial hemorrhage risk compared to late resumption (31–365 days): 3.12% vs 3.27%, adjusted HR 0.967 (95% CI 0.522–1.791). 8

• Delayed traumatic intracranial hemorrhage after normal initial CT is rare: 0.6% in warfarin patients and 0% in clopidogrel patients, supporting safe discharge with appropriate instructions after 24-hour observation. 5

Location-Specific Considerations

Deep Hemorrhage (Basal Ganglia, Thalamus, Brainstem)

• Antiplatelet resumption is reasonable as recurrence risk is substantially lower than lobar hemorrhages 1
• Follow standard timing guidelines (7–10 days for very high risk, 4 weeks for standard risk)

Lobar Hemorrhage (Cortical/Subcortical)

• Generally avoid long-term antiplatelet therapy due to 15% annual recurrence risk, likely from underlying cerebral amyloid angiopathy 1, 2
• Only resume if thromboembolism risk dramatically exceeds bleeding risk (e.g., mechanical mitral valve)

Special Populations

Patients on Clopidogrel Pre-Injury

• Clopidogrel patients have 2.3-fold higher prevalence of immediate traumatic intracranial hemorrhage (12.0%) compared to warfarin patients (5.1%) 5
• Clopidogrel patients are 5.1 times more likely to have progression on repeat CT and 1.8 times more likely to require neurosurgical intervention 4
• No delayed traumatic intracranial hemorrhage was observed in 243 clopidogrel patients followed for 2 weeks 5

Elderly Patients with Lobar Hemorrhage

• Higher risk of cerebral amyloid angiopathy warrants more conservative approach to antiplatelet resumption 2
• Consider aspirin as bridge therapy only if anticoagulation indication exists (e.g., atrial fibrillation) until safer timepoint for anticoagulation 1

Critical Pitfalls to Avoid

• Never resume antiplatelet therapy before repeat imaging confirms hemorrhage stability 1, 2
• Never restart dual antiplatelet therapy routinely after traumatic intracranial hemorrhage—bleeding risk outweighs benefit 2
• Never resume before 7 days unless patient has mechanical prosthetic valve with extreme thrombosis risk 1
• Never ignore hemorrhage location—lobar hemorrhages have dramatically higher recurrence risk than deep hemorrhages 1, 2
• Do not automatically restart therapy without reassessing the original indication—if indication was primary prevention only, consider withholding permanently 1