Lp(a) and thromboembolism: current state of knowledge and unsolved issues

Lipoprotein(a) [Lp(a)], a low-density lipoprotein-like particle containing apolipoprotein(a) [apo(a)], is a genetically determined independent risk factor for cardiovascular disease. Elevated Lp(a) levels, present in ~20% of Europeans, are linked to myocardial infarction, ischemic stroke, calcific aortic valve disease, and other cardiac events. Its role in venous thromboembolism (VTE) remains controversial despite shared arterial and venous mechanisms. Elevated Lp(a), particularly smaller apo(a) isoforms, exhibits antifibrinolytic effects by inhibiting plasminogen activation via interactions with plasminogen, tissue-type plasminogen activator, and fibrin. Prothrombotic mechanisms include increased plasminogen activator inhibitor-1 (PAI-1) production, formation of denser fibrin networks, platelet activation, enhanced oxidation of phospholipids, and tissue factor dysregulation. Emerging therapies targeting Lp(a) could reduce thromboembolic risks. This review summarizes Lp(a)'s prothrombotic and antifibrinolytic actions, clinical associations with thromboembolism, and the role of oxidized phospholipids in explaining discrepancies in VTE-related findings.