From the Guidelines
Antiphospholipid antibodies cause strokes in young patients primarily through hypercoagulability, which is triggered by the interaction of these antibodies with phospholipids and phospholipid-binding proteins on cell membranes, particularly in platelets and endothelial cells, as supported by the most recent guidelines 1. The pathophysiology involves the activation of platelets, damage to endothelial cells, interference with natural anticoagulant proteins, promotion of complement activation, and impairment of fibrinolysis, creating a high-risk environment for arterial thrombosis in cerebral vessels, resulting in ischemic strokes even in young individuals without traditional cardiovascular risk factors. Key points to consider in the management of antiphospholipid syndrome include:
- The association between antiphospholipid antibodies and stroke is strongest for young adults (<50 years of age) 1.
- Treatment typically involves long-term anticoagulation with warfarin (target INR 2-3), or in some cases, direct oral anticoagulants, though warfarin remains the standard of care for these patients 1.
- The use of direct oral anticoagulants instead of warfarin is still a topic of debate, with some studies suggesting that they may be less effective in reducing the risk of stroke in patients with antiphospholipid syndrome 1.
- The role of dual antiplatelets in antiphospholipid syndrome is also unclear, with some reports suggesting a possible preventive role or in addition to anticoagulation 1. Some of the key recommendations for the management of antiphospholipid syndrome include:
- In patients with ischemic stroke or TIA who have an isolated antiphospholipid antibody but do not fulfill the criteria for antiphospholipid syndrome, antiplatelet therapy alone is recommended to reduce the risk of recurrent stroke 1.
- In patients with ischemic stroke or TIA with confirmed antiphospholipid syndrome treated with warfarin, it is reasonable to choose a target INR between 2 and 3 over a target INR >3 to effectively balance the risk of excessive bleeding against the risk of thrombosis 1.
- In patients with ischemic stroke or TIA who meet the criteria for the antiphospholipid syndrome, it is reasonable to anticoagulate with warfarin to reduce the risk of recurrent stroke or TIA 1.
From the Research
Mechanism of Antiphospholipid Antibodies (aPL) in Causing Stroke
- Antiphospholipid antibodies (aPL) are associated with an increased risk of thrombotic events, including stroke, in patients with antiphospholipid syndrome (APS) 2, 3, 4, 5, 6.
- The exact mechanism by which aPL cause stroke is not fully understood, but it is thought to involve the activation of platelets and the coagulation cascade, leading to the formation of blood clots 3, 6.
- aPL can also cause endothelial damage and inflammation, which can contribute to the development of thrombosis 6.
Risk Factors for Stroke in Patients with aPL
- Patients with aPL are at increased risk of stroke, particularly those with a history of previous thrombotic events 4, 5.
- The risk of stroke is also increased in patients with high levels of aPL, such as those with triple positivity 3, 5.
- Other risk factors for stroke in patients with aPL include the presence of other autoimmune disorders, such as systemic lupus erythematosus, and the use of certain medications, such as oral contraceptives 6.
Treatment and Prevention of Stroke in Patients with aPL
- Anticoagulation therapy, such as warfarin, is the mainstay of treatment for patients with aPL and a history of thrombotic events 2, 3, 4, 5.
- The use of direct oral anticoagulants (DOACs) is not recommended for patients with aPL and a history of arterial thrombosis or triple positivity 3, 5.
- Antiplatelet therapy, such as aspirin, may be used in combination with anticoagulation therapy to prevent recurrent thrombotic events 4, 6.
- Lifestyle modifications, such as smoking cessation and regular exercise, can also help to reduce the risk of stroke in patients with aPL 6.