Administration of Low-Molecular-Weight Heparin After Hemorrhagic Stroke: What Is the Appropriate Timing?
Hemorrhagic stroke (HS) is a condition that raises doubts and concerns about anticoagulation. Is early prevention of thromboembolic complications appropriate?
Introduction
Patients with primary intracerebral hemorrhage are at a proven increased risk of venous thromboembolism. It appears that without preventive measures, deep vein thrombosis will occur in about half of stroke patients (47−53%), and 3−16% of them will die from pulmonary embolism. Especially in those with hemiparesis/hemiplegia, the risk of developing thromboembolic disease is very high (75%). VTE represents a potentially fatal complication entering a clinical condition that is already life-threatening for the patient, and it increases the monthly fatality rate from 35 to 52%.
Thromboembolic disease following primary intracerebral hemorrhage worsens the patient's prognosis. Early administration of low-molecular-weight heparin (LMWH) for the prevention of VTE theoretically can increase the size of the hematoma, while late administration may reduce the effectiveness in preventing thromboembolism.
Based on randomized controlled trials, intermittent pneumatic compression along with long compression stockings and LMWH is recommended in American and European guidelines for the prevention of thromboembolic disease in patients with acute stroke. However, these guidelines are based on studies with small cohorts of subjects and a heterogeneous approach to stroke diagnosis without restriction to intracerebral hemorrhage only. Therefore, the question of timing for administering low-molecular-weight heparin in patients with hemorrhagic stroke remained unclear.
Methodology and Study Course
A recent multicenter double-blind placebo-controlled study in Finland aimed to define the correct timing for low-molecular-weight heparin application in preventing thromboembolic disease in patients with hemorrhagic stroke and a paretic lower limb. The authors practically focused on answering which risk (hematoma enlargement associated with LMWH vs. thromboembolic complication) poses a greater threat to the patient.
Patients older than 18 years with a paretic lower limb admitted to the emergency room within 12 hours of the onset of symptomatic intracerebral hemorrhage were included. They were randomized into 2 groups: subjects in the enoxaparin group received 20 mg of this drug 2× daily from 24 hours after admission to hospitalization, while in the placebo group, the active drug was administered only from the 72nd hour after admission. Both groups were immediately given pneumatic compression stockings. Patients were examined for deep vein thrombosis and hemorrhagic complications 1 day after study entry and again before discharge.
Results
A total of 139 patients entered the study. Only 3 of them developed deep vein thrombosis, one in the group that received early enoxaparin and two in the group that started receiving it after 72 hours. No participant in the study developed pulmonary embolism. The occurrence of thromboembolic events (p = 0.901), the risk of hematoma enlargement (p = 0.927), and the overall clinical outcome (p = 0.904) did not significantly differ between the groups.
Conclusion
The administration of enoxaparin at a dose of 40 mg daily for the prevention of thromboembolism in patients with spontaneous intracerebral hemorrhage is safe regardless of whether it was started 24 or 72 hours after hemorrhage. Early administration of enoxaparin is not associated with the risk of enlarging the hemorrhagic lesion.
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Source:
Qian C., Huhtakangas J., Juvela S. et al. Early vs. late enoxaparin for the prevention of venous thromboembolism in patients with ICH: a double blind placebo controlled multicenter study. Clin Neurol Neurosurg 2021 Mar; 202: 106534, doi: 10.1016/j.clineuro.2021.106534.
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