Review: Antiphospholipid Antibodies and Cardiovascular Thrombosis

Antiphospholipid antibodies (aPL) are directed against phospholipids and phospholipid-binding proteins. Laboratory assays used to detect aPL include serological tests for aPL against β₂-glycoprotein 1, cardiolipin and other molecules, as well as functional assays for lupus anticoagulant. The presence of aPL can lead to endothelial dysfunction or a hypercoagulable state through prothrombotic and antifibrinolytic mechanisms. These processes, often in conjunction with a ‘second hit’, such as trauma, surgery, or other causes of hypercoagulability or stasis, can lead to venous or arterial thrombosis. The thrombotic risk associated with aPL is best recognized in thrombotic antiphospholipid syndrome, characterized by a persistently positive test for lupus anticoagulant or seropositivity for aPL associated with venous, arterial or microvascular thrombosis. However, aPL seropositivity and its clinical effect on thrombotic events have been increasingly recognized in a broader group of individuals who do not meet traditional research criteria for thrombotic antiphospholipid syndrome. In this Review, we provide an overview of the evidence related to aPL seropositivity in individuals with or without previous thrombosis and the clinical relevance of aPL seropositivity in predicting the risk of thrombotic cardiovascular events. We discuss potential management strategies and identify key knowledge gaps that warrant further research.

• Antiphospholipid antibodies (aPL) are directed against phospholipids and phospholipid-binding proteins, including β₂-glycoprotein 1 (β₂-GP1), cardiolipin, phosphatidylserine and prothrombin; lupus anticoagulant is assessed by functional tests that identify aPL.
• Thrombotic antiphospholipid syndrome (APS) is a rare condition associated with persistently elevated aPL, thrombotic events, and a high risk of recurrent events.
• In patients with thrombotic APS, direct oral anticoagulants are less effective than vitamin K antagonists for reducing the risk of subsequent thrombotic events.
• Emerging data indicate that seropositivity for aPL is common among patients not fulfilling the traditional criteria for APS and portends an excess risk of venous and arterial thrombotic events.
• Studies are needed to identify the best treatment options for patients with aPL seropositivity who do not fulfil the traditional criteria for APS.