Can I give Low Molecular Weight Heparin (LMWH) twice a day in embolic stroke?

LMWH Dosing in Embolic Stroke

For prophylactic VTE prevention in embolic stroke, LMWH should be given once daily, not twice daily, with the preferred regimen being enoxaparin 40 mg subcutaneously once daily starting 24-48 hours after stroke onset. 1

Prophylactic Dosing (VTE Prevention)

The standard prophylactic approach uses once-daily dosing:

• Enoxaparin 40 mg subcutaneously once daily is the evidence-based regimen that proved superior to unfractionated heparin 5000 IU twice daily in the PREVAIL trial 1
• Prophylactic-dose LMWH is defined as 3,000-6,000 International Units per day, typically given as a single daily injection 1
• LMWH is preferred over unfractionated heparin for thromboprophylaxis in stroke patients with restricted mobility 1, 2

Timing Considerations

Critical timing restrictions apply:

• Initiate prophylactic LMWH within 24-48 hours after stroke onset 1, 2
• Do not use within the first 24 hours after thrombolytic therapy 1
• For large ischemic strokes, delay anticoagulation for 5-7 days due to hemorrhagic transformation risk 2
• For hemorrhagic transformation (HI2, PH1, PH2), prophylactic anticoagulation is absolutely contraindicated 2

Therapeutic Dosing (Not Recommended for Acute Stroke)

Twice-daily therapeutic dosing is NOT recommended for acute embolic stroke treatment:

• The HAEST trial showed dalteparin 100 U/kg subcutaneously twice daily provided no benefit over aspirin in atrial fibrillation-related stroke, with similar rates of recurrent stroke (8.5% vs 7.5%) and hemorrhage (12% vs 14%) 1
• Multiple guidelines conclude that therapeutic anticoagulation with LMWH has not been shown to reduce stroke recurrence and increases hemorrhage risk 1
• Early aspirin therapy (160-325 mg) is recommended over therapeutic parenteral anticoagulation 3, 2

Evidence Against Twice-Daily Dosing in Acute Stroke

The data consistently show no benefit from therapeutic twice-daily regimens:

• Studies testing nadroparin 4100 anti-Xa IU twice daily showed no reduction in death or dependence at 3 months compared to placebo 1
• The TOPAS trial comparing various certoparin doses (including twice-daily regimens) found no benefit in stroke outcomes 1
• Meta-analyses demonstrate that LMWHs significantly reduce DVT but do not improve stroke outcomes when used at therapeutic doses 1

Special Populations

For embolic stroke from atrial fibrillation:

• Start aspirin 160-325 mg within 48 hours, not therapeutic LMWH 3, 2
• Transition to oral anticoagulation within 2 weeks for secondary prevention 3
• Bridging with therapeutic-dose LMWH is not routinely recommended 1

For large artery occlusive disease:

• One post-hoc analysis suggested LMWH may reduce early neurologic deterioration in this subgroup 4
• However, this remains investigational and is not standard practice 1

Common Pitfalls

Avoid these errors:

• Do not confuse prophylactic (once daily) with therapeutic (twice daily) dosing - the question likely refers to prophylaxis, which is once daily 1
• Do not use therapeutic-dose LMWH to prevent early recurrent embolism - trials show increased hemorrhage without proven benefit 1
• Do not start LMWH immediately after thrombolysis - wait at least 24 hours 1
• Do not use in patients with hemorrhagic transformation or large infarcts at high risk for bleeding 2

Bottom Line Algorithm

For embolic stroke patients:

1. If immobilized and at risk for DVT: Give enoxaparin 40 mg subcutaneously once daily starting 24-48 hours post-stroke 1, 2
2. If received thrombolysis: Wait 24 hours before starting prophylactic LMWH 1
3. If large infarct (>1/3 MCA territory): Delay 5-7 days 2
4. If hemorrhagic transformation on imaging: Contraindicated 2
5. For stroke prevention: Use aspirin or oral anticoagulation, not therapeutic LMWH 3, 2