What is the role of heparin (unfractionated heparin) in the management of patients with large cortical stroke?

Heparin in Large Cortical Stroke

Unfractionated heparin is not recommended for routine treatment of patients with large cortical stroke due to increased risk of serious bleeding complications without proven benefit in improving neurological outcomes or preventing early recurrent stroke. 1, 2

Evidence Against Routine Heparin Use

Lack of Efficacy

• Multiple guidelines consistently demonstrate that urgent anticoagulation with heparin does not improve neurological outcomes or prevent early recurrent stroke in patients with acute ischemic stroke 2
• The American Academy of Neurology and American Stroke Association explicitly recommend against using heparin drip in acute stroke, regardless of stroke subtype 1
• International Stroke Trial (IST) found no significant differences between low-dose heparin and no heparin in 14-day mortality or pulmonary embolism 1

Increased Bleeding Risk

• Parenterally administered anticoagulants (heparin, LMW heparins, or heparinoid) significantly increase the risk of serious bleeding complications 2
• Higher risk of symptomatic hemorrhagic transformation of ischemic strokes, especially among patients with severe strokes 2
• In the IST study, 1.2% of patients given subcutaneous heparin had a hemorrhagic stroke compared with 0.4% of control participants (p < 0.0001) 2
• Systemic hemorrhage requiring transfusion occurred in 1.3% of heparin-treated patients compared with 0.4% for control participants (p < 0.00001) 2

Specific Recommendations for Large Cortical Stroke

Current Guideline Position

• Urgent anticoagulation is specifically not recommended for treatment of patients with moderate-to-severe stroke (which includes large cortical strokes) because of a high risk of serious intracranial bleeding complications (grade A recommendation) 2
• No stroke subgroup, including large cortical strokes, has demonstrated clear benefit from heparin drip therapy 1

Timing Considerations

• Initiation of anticoagulant therapy within 24 hours of treatment with intravenously administered rtPA is contraindicated 2
• Parenteral anticoagulants should not be prescribed until a brain imaging study has excluded the possibility of a primary intracranial hemorrhage 2

Limited Potential Exceptions

Specific Clinical Scenarios

• A subgroup analysis from one trial found that an anticoagulant might improve the chances of favorable outcomes among patients with stroke secondary to large artery atherosclerosis (level II evidence) 2, but this finding requires further validation
• Some research suggests potential benefit in specific subpopulations such as patients with symptomatic large artery stenosis >70%, non-occlusive intraluminal thrombus, and high-risk cardiac conditions 3, 4
• A small study suggested possible benefit when heparin was started within the first 3 hours after onset of symptoms in nonlacunar hemispheric cerebral infarctions, but with increased risk of symptomatic brain hemorrhages 5

Appropriate Alternatives

Recommended Antithrombotic Therapy

• Aspirin (160-325 mg/day) should be administered within 24-48 hours after stroke onset after excluding intracranial hemorrhage 1
• For patients treated with IV alteplase (tPA), aspirin administration should be delayed until 24 hours later 1
• Early aspirin administration reduces stroke mortality and decreases morbidity primarily by reducing early recurrent stroke 1

DVT Prophylaxis

• Low-dose subcutaneous unfractionated heparin or LMWH may be considered only for DVT prophylaxis in at-risk patients, not for stroke treatment 1
• The level of anticoagulation should be closely monitored if a patient is receiving these medications 2

Common Pitfalls to Avoid

• Assuming heparin prevents early recurrent stroke is not supported by evidence 1
• Using heparin for "stroke in evolution" lacks supporting evidence 1
• Assuming benefit in cardioembolic stroke is not supported by evidence, despite theoretical benefits 1
• Confusing low-dose subcutaneous heparin for DVT prevention with therapeutic heparin drip for stroke treatment 1

In conclusion, the evidence strongly advises against the routine use of unfractionated heparin in patients with large cortical stroke, with aspirin being the preferred antithrombotic agent in the acute setting unless specifically contraindicated.