When should prophylactic enoxaparin be started after IV alteplase thrombolysis for stroke, and how should the dose be adjusted for renal impairment?

When to Start DVT Prophylaxis Enoxaparin After IV Alteplase for Stroke

Delay enoxaparin prophylaxis for at least 24 hours after IV alteplase administration for acute ischemic stroke, and only after obtaining a follow-up CT or MRI scan to exclude hemorrhagic transformation. 1

Timing of Anticoagulation After Thrombolysis

The 2018 AHA/ASA Stroke Guidelines provide clear direction on this critical safety issue:

• Obtain a follow-up CT or MRI scan at 24 hours after IV alteplase before starting anticoagulants or antiplatelet agents 1
• The risk of antithrombotic therapy within the first 24 hours after IV alteplase treatment is uncertain (Class IIb, Level B-NR) 1
• Use of anticoagulation within 24 hours might be considered only in the presence of concomitant conditions where withholding treatment is known to cause substantial risk 1

Critical Safety Window

• No anticoagulation or antiplatelet therapy should be initiated for at least 24 hours post-alteplase unless there is a compelling indication that outweighs hemorrhagic risk 1
• Blood pressure must be maintained below 180/105 mm Hg for the entire first 24 hours after alteplase treatment 1
• Neurological assessments should be performed every 15 minutes during and for 2 hours after infusion, then every 30 minutes for 6 hours, then hourly until 24 hours 1

Standard Enoxaparin Dosing for DVT Prophylaxis

Once the 24-hour window has passed and imaging excludes hemorrhage:

• Standard prophylactic dose: 40 mg subcutaneously once daily 2
• Continue for the duration of hospital stay or until the patient is fully ambulatory 2

Dose Adjustments for Renal Impairment

For patients with severe renal impairment (creatinine clearance <30 mL/min), reduce the dose to 30 mg subcutaneously once daily 2, 3, 4

Renal Function Considerations

• Enoxaparin clearance is reduced by 31% in moderate renal impairment and 44% in severe renal impairment 2
• Failure to adjust dosing in severe renal impairment results in a 2-3 fold increased bleeding risk 3
• For moderate renal impairment (CrCl 30-60 mL/min), standard dosing may be used but consider monitoring anti-Xa levels in high-risk patients 5, 6

Monitoring Requirements in Renal Impairment

• For severe renal impairment on prolonged therapy, monitor anti-Xa levels targeting 0.2-0.5 IU/mL for prophylaxis 2, 3
• Measure anti-Xa levels 4-6 hours after dosing, after 3-4 consecutive doses have been given 2

Special Populations and Additional Adjustments

Obesity

• For patients with BMI >30 kg/m² or class III obesity, consider 40 mg subcutaneously every 12 hours or 0.5 mg/kg every 12 hours 2

Elderly Patients

• Elderly patients (≥70 years) with renal insufficiency require extreme caution due to drug accumulation risk 3

Common Pitfalls to Avoid

• Never start enoxaparin before 24 hours post-alteplase without imaging confirmation of no hemorrhage – this is the most critical error that can lead to catastrophic intracranial bleeding 1
• Do not use standard 40 mg daily dosing in patients with CrCl <30 mL/min – this leads to drug accumulation and 4-fold increased bleeding risk 3
• Avoid placement of indwelling catheters if possible during the first 24 hours to minimize bleeding complications 1
• Do not initiate enoxaparin if blood pressure cannot be maintained below 180/105 mm Hg 1

Clinical Algorithm

1. Administer IV alteplase for eligible acute ischemic stroke patients 1
2. Monitor blood pressure and neurological status intensively for 24 hours 1
3. Obtain follow-up CT or MRI at 24 hours to exclude hemorrhagic transformation 1
4. If imaging is clear and patient requires DVT prophylaxis:
   • Calculate creatinine clearance
   • If CrCl ≥30 mL/min: start enoxaparin 40 mg SC once daily 2
   • If CrCl <30 mL/min: start enoxaparin 30 mg SC once daily 2, 3
   • If BMI ≥40 kg/m²: consider 40 mg SC every 12 hours 2
5. Continue prophylaxis until fully ambulatory or hospital discharge 2