In an adult with acute ischemic (thrombotic) stroke, what enoxaparin dose is recommended for venous‑thromboembolism prophylaxis and for therapeutic anticoagulation, including renal‑function adjustments and timing after intravenous alteplase?

Enoxaparin Dosing in Acute Ischemic Stroke Patients

VTE Prophylaxis: Standard Dosing

For venous thromboembolism prophylaxis in acute ischemic stroke patients, administer enoxaparin 40 mg subcutaneously once daily, starting after neurological stability is confirmed and continuing throughout hospitalization or until the patient regains independent mobility. 1

Evidence Supporting Enoxaparin Over Unfractionated Heparin

• The PREVAIL trial demonstrated that enoxaparin 40 mg once daily reduced VTE risk by 43% compared to unfractionated heparin 5000 U every 12 hours (10% vs 18%; relative risk 0.57,95% CI 0.44–0.76; P=0.0001), with similar bleeding rates between groups. 2

• Enoxaparin provides superior VTE prevention without increasing symptomatic intracranial hemorrhage compared to UFH (1% vs 1%; P=0.55), though major extracranial bleeding was slightly higher (1% vs 0%; P=0.015). 2

• A 2024 observational study found that enoxaparin prophylaxis resulted in significantly fewer intracranial hemorrhages compared to UFH (0% vs 3.9%; P<0.05) in stroke patients, with comparable VTE rates. 3

Duration and Timing

• Continue prophylactic enoxaparin throughout the acute hospitalization and rehabilitation stay, or until the patient regains full mobility. 1

• For patients discharged directly home with mild motor impairments, VTE prophylaxis may not be needed. 1

Critical Timing After IV Alteplase

Do not administer any anticoagulant—including prophylactic enoxaparin—for at least 24 hours after IV alteplase administration, and only after follow-up CT or MRI confirms no hemorrhagic transformation. 4

Post-Thrombolysis Protocol

• Obtain mandatory follow-up neuroimaging exactly 24 hours after alteplase before starting any antithrombotic therapy. 4

• Maintain blood pressure below 180/105 mm Hg throughout the first 24 hours post-alteplase. 4

• Perform neurological assessments every 15 minutes during and for 2 hours after alteplase infusion, then every 30 minutes for 6 hours, then hourly until 24 hours. 4

• The restriction on anticoagulation within 24 hours of alteplase is based on increased bleeding risk demonstrated in clinical trials; early administration does not reduce early recurrent stroke or neurological worsening. 1

Renal Function Adjustments

For patients with severe renal impairment (creatinine clearance <30 mL/min), reduce the prophylactic dose to 30 mg subcutaneously once daily. 1, 4

Pharmacokinetic Rationale

• Enoxaparin clearance is reduced by 44% in severe renal impairment, increasing bleeding risk 2- to 3-fold with standard dosing. 1, 4

• For moderate renal impairment (CrCl 30–60 mL/min), enoxaparin clearance decreases by 31%; some evidence supports dose reduction, though not universally mandated. 1

• Monitor anti-Xa levels (target 0.5–1.5 IU/mL) in patients with CrCl <30 mL/min receiving prolonged therapy, measured 4–6 hours after the dose following 3–4 consecutive doses. 1, 4

Obesity Considerations

For patients with BMI >30 kg/m² or class III obesity, consider intermediate-dose prophylaxis of 40 mg subcutaneously every 12 hours or weight-based dosing at 0.5 mg/kg every 12 hours. 4

• A 2024 study found that 19% of rehabilitation patients receiving fixed 40 mg daily dosing had sub-prophylactic anti-Xa levels, with weight inversely correlating with enoxaparin activity. 5

• Standard fixed dosing may be inadequate in obese patients and excessive in very low-weight patients (<50 kg). 4

Therapeutic Anticoagulation: Reserved for Specific Indications

Therapeutic-dose enoxaparin (1 mg/kg subcutaneously every 12 hours) is NOT indicated for routine stroke management but should be used only for established indications such as acute coronary syndrome, atrial fibrillation with high stroke risk, or confirmed venous thromboembolism. 4

Therapeutic Dosing When Indicated

• For confirmed VTE in stroke patients, administer enoxaparin 1 mg/kg subcutaneously every 12 hours or 1.5 mg/kg once daily. 4

• In severe renal impairment (CrCl <30 mL/min), reduce therapeutic dosing to 1 mg/kg once every 24 hours. 1, 4

• The usefulness of urgent anticoagulation for arterial dissection or vertebrobasilar disease has not been established. 1

Safety Monitoring

• Monitor platelet counts every 2–3 days from day 4 through day 14 to screen for heparin-induced thrombocytopenia, though enoxaparin carries substantially lower HIT risk than UFH (≈1% vs up to 5%). 4

• Routine anti-Xa monitoring is not necessary for patients with normal renal function receiving standard prophylactic dosing. 4, 5

Common Pitfalls to Avoid

• Never start enoxaparin before 24 hours post-alteplase without imaging confirmation of no intracranial hemorrhage—this can cause catastrophic bleeding. 4

• Do not use standard dosing in severe renal impairment—failure to adjust for CrCl <30 mL/min leads to drug accumulation and 2- to 3-fold increased bleeding risk. 1, 4

• Avoid elastic compression stockings—they are not useful for VTE prophylaxis in ischemic stroke and increase skin complications. 1

• Do not confuse prophylactic with therapeutic indications—therapeutic-dose enoxaparin is not indicated for routine stroke management and does not prevent early recurrent stroke. 1, 4