When should anticoagulation be initiated after a watershed stroke?

From the Guidelines

Anticoagulation should be initiated 4-14 days after a watershed stroke, depending on the size of the infarct and risk of hemorrhagic transformation, as recommended by the most recent guidelines 1. The decision to anticoagulate should be based on the underlying cause of the stroke, with atrial fibrillation, hypercoagulable states, and severe carotid stenosis being common indications.

• For small watershed strokes without hemorrhagic components, anticoagulation may be started as early as 4 days after the event,
• while larger strokes may require waiting 7-14 days. Common anticoagulants include warfarin (target INR 2-3), direct oral anticoagulants like apixaban (5mg twice daily), rivaroxaban (20mg daily), or dabigatran (150mg twice daily), or low molecular weight heparins like enoxaparin (1mg/kg twice daily). Before initiating anticoagulation, a follow-up brain imaging study (CT or MRI) should be performed to rule out hemorrhagic transformation, as suggested by the European Heart Rhythm Association practical guide 1. The timing balances the risk of recurrent ischemic events against the risk of hemorrhagic transformation, which is highest in the first few days after a stroke when the blood-brain barrier is compromised and infarcted tissue is most vulnerable to bleeding, as noted in the 2018 Canadian Stroke Best Practice Recommendations 1 and the 2018 Chest guideline 1. It is also important to consider the size of the cerebral infarct, as patients with larger infarcts are at greater risk for hemorrhagic transformation and worse bleeding with early initiation of anticoagulation, as stated in the 2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack 1.

From the Research

Timing of Anticoagulation after Watershed Stroke

The optimal timing for initiating anticoagulation after a watershed stroke is a complex decision that depends on various factors, including the patient's underlying condition, the risk of recurrent stroke, and the risk of bleeding.

• The risk of early recurrent ischemic stroke in patients with atrial fibrillation may be high, and anticoagulation is essential for secondary stroke prevention 2.
• However, the timing of anticoagulation initiation after a watershed stroke is not well established, and current guidelines provide imprecise recommendations 3.
• Some studies suggest that early anticoagulation (within 3-5 days) may be associated with a low frequency of clinically symptomatic intracranial hemorrhage or surrogate hemorrhagic lesions on MRI scans, whereas later anticoagulation initiation (ie, >7 days or >14 days after index stroke) may be associated with an increased frequency of recurrent ischemic stroke 2.
• A case report suggests that anticoagulation can be safely initiated as early as 6 days after the onset of hemorrhage transformation in patients with mechanical heart valves and antithrombin deficiency 4.
• Another study found that anticoagulation may be safely used in some patients with hemorrhagic infarction, even if the CT appearance of hemorrhagic infarction is present 5.

Factors Influencing Anticoagulation Timing

Several factors can influence the timing of anticoagulation after a watershed stroke, including:

• The presence of mechanical heart valves or other cardiac conditions that increase the risk of thromboembolism 4, 3.
• The severity of the stroke and the presence of hemorrhagic transformation 3, 2.
• The patient's bleeding risk profile and the risk of recurrent stroke 6.
• The choice of anticoagulant, with direct oral anticoagulants (DOACs) potentially being preferred over warfarin due to decreased bleeding risks 2, 6.