Thrombosis, Inflammation, and Lipoprotein(a): Clinical Implications

Multiple mechanisms mediate thrombus formation, including activation of platelets, coagulation, and fibrinolysis. This chapter discusses the complexity of interactions between lipoprotein(a) (Lp(a)), coagulation, fibrinolytic, and inflammatory factors. Lp(a), apo(a), and its fragments can bind to the extracellular matrix of arterial and venous walls. Elevated levels of Lp(a) mediate thrombus formation and slow plasmin generation, while apo(a) can inactivate tissue factor pathway inhibitor promoting blood coagulation. Changing conditions of blood flow and high shear stress impact the interplay between thrombus development in the arterial and venous systems. Oxidation of Lp(a) increases clot density. The oxidized phospholipids (oxPL)-Lp(a) complex has been shown to upregulate adhesion molecules, increase secretion of chemo-attractants and cytokines, interact with various signal transduction receptors on the cell surface, and modulate binding of leukocytes to endothelial cells. Smaller apo(a) isoforms demonstrate stronger association with oxPL. In this chapter, we review clinical relevance and implications of pro-thrombotic and pro-inflammatory states associated with Lp(a). Further investigation of the role of Lp(a)-targeted therapies in mediating levels of pro-inflammatory, pro-thrombotic, and antifibrinolytic markers and their effects on clinical outcomes is needed.