What is the management for a patient experiencing a cerebral hemorrhage headache while on Lovenox (enoxaparin) and warfarin?

Management of Intracranial Hemorrhage in Patients on Lovenox and Warfarin

Immediately discontinue both anticoagulants, urgently reverse warfarin with 4-factor prothrombin complex concentrate (4F-PCC) plus intravenous vitamin K, and reverse therapeutic-dose Lovenox with protamine sulfate. 1

Immediate Anticoagulation Reversal

Warfarin Reversal

• Administer 4-factor prothrombin complex concentrate (4F-PCC) to achieve INR <1.5, along with 5mg intravenous vitamin K. 2
• Vitamin K alone is inadequate as it does not reverse the hemostatic defect for many hours. 3
• The goal is urgent reversal given the 50% mortality rate associated with warfarin-related intracranial hemorrhage. 3, 4

Lovenox (Enoxaparin) Reversal

• 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

Prophylactic vs. Therapeutic Dosing Considerations

• Do not routinely reverse prophylactic subcutaneous heparin/enoxaparin unless the activated partial thromboplastin time (aPTT) is significantly prolonged. 1
• However, therapeutic-dose LMWH in the setting of intracranial hemorrhage requires reversal. 1

Immediate Diagnostic and Monitoring Steps

Imaging Protocol

• Obtain immediate non-contrast head CT to confirm and characterize the hemorrhage. 1, 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, 5
• Consider CT angiography to identify patients at risk for hematoma expansion based on contrast extravasation. 1

Laboratory Monitoring

• 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

Neurosurgical Consultation

• Obtain immediate neurosurgical consultation for all patients with confirmed intracranial hemorrhage on anticoagulation. 2, 6
• Surgical intervention may be necessary depending on hemorrhage location, size, and clinical deterioration. 1

Additional Hemostatic Measures

Antifibrinolytic Therapy

• Consider tranexamic acid 1g IV over 10 minutes if treatment can be given within 3 hours of symptom onset. 2
• This reduces head injury-related death with a risk ratio of 0.78 (95% CI 0.64-0.95). 2

Cryoprecipitate

• If thrombolytic agents were recently administered (within 24 hours), administer cryoprecipitate 10 units as initial dose. 1

Common Pitfalls to Avoid

• Do not rely on vitamin K alone for warfarin reversal—it takes many hours to work and is inadequate for acute intracranial hemorrhage. 3
• 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

Resumption of Anticoagulation

• For patients with mandatory indications for anticoagulation (mechanical heart valves), consider resuming warfarin within 3-10 days if the patient is stable and hemorrhage is not expanding. 3
• For patients with atrial fibrillation, the decision to resume anticoagulation is more controversial and should be individualized based on thromboembolic risk versus bleeding risk. 3
• Arrange outpatient follow-up for reassessment of anticoagulation risk/benefit ratio and fall risk assessment. 2, 6

Observation and Follow-Up

• Admit all patients with intracranial hemorrhage on anticoagulation to an intensive care unit with dedicated neurological specialists. 7
• Monitor neurologically with documented half-hourly checks until stable. 5
• Any neurological deterioration requires immediate repeat CT imaging. 5