Management of Intracranial Hemorrhage in Patients on Anticoagulants

Immediate Anticoagulation Reversal

The American College of Critical Care Medicine recommends immediately discontinuing both anticoagulants, urgently reversing warfarin with 4-factor prothrombin complex concentrate (4F-PCC) plus intravenous vitamin K, and reversing therapeutic-dose Lovenox with protamine sulfate in patients with intracranial hemorrhage on Lovenox and Warfarin 1
Administer 4-factor prothrombin complex concentrate (4F-PCC) to achieve INR <1.5, along with 5mg intravenous vitamin K for warfarin reversal 2
Reverse therapeutic-dose enoxaparin with protamine sulfate administered by slow IV injection over 10 minutes 1
If enoxaparin was given within 8 hours, administer 1 mg protamine per 1 mg of enoxaparin (maximum single dose 50 mg) 1
If enoxaparin was given within 8-12 hours, administer 0.5 mg protamine per 1 mg of enoxaparin 1
After 3-5 half-lives have elapsed, protamine is probably not needed 1
If life-threatening bleeding persists or the patient has renal insufficiency, redose protamine at 0.5 mg per 1 mg of enoxaparin 1
Do not routinely reverse prophylactic subcutaneous heparin/enoxaparin unless the activated partial thromboplastin time (aPTT) is significantly prolonged 1
Therapeutic-dose LMWH in the setting of intracranial hemorrhage requires reversal 1

Obtain immediate non-contrast head CT to confirm and characterize the hemorrhage 3, 2
Obtain repeat head CT within 24 hours, as anticoagulated patients have a 3-fold increased risk of hemorrhage expansion (26% versus 9% in non-anticoagulated patients) 2, 4
Consider CT angiography to identify patients at risk for hematoma expansion based on contrast extravasation 3
Check INR, PT, aPTT, and fibrinogen levels immediately 1
Recheck INR after reversal agents are administered to confirm adequate reversal 1
If fibrinogen is less than 150 mg/dL after reversal, administer additional cryoprecipitate 1

Obtain immediate neurosurgical consultation for all patients with confirmed intracranial hemorrhage on anticoagulation 2, 5
Surgical intervention may be necessary depending on hemorrhage location, size, and clinical deterioration 3

Consider tranexamic acid 1g IV over 10 minutes if treatment can be given within 3 hours of symptom onset, which reduces head injury-related death with a risk ratio of 0.78 (95% CI 0.64-0.95) 2
If thrombolytic agents were recently administered (within 24 hours), administer cryoprecipitate 10 units as initial dose 1

Do not use protamine for reversal of pentasaccharides (fondaparinux)—it is ineffective 1
Do not delay reversal while waiting for laboratory confirmation if clinical suspicion is high 1
Do not assume prophylactic-dose enoxaparin is safe to leave unreversed—check the aPTT and consider reversal if significantly prolonged 1

Monitor neurologically with documented half-hourly checks until stable 4
Any neurological deterioration requires immediate repeat CT imaging 4
Arrange outpatient follow-up for reassessment of anticoagulation risk/benefit ratio and fall risk assessment 2, 5