Mechanisms of thrombosis in obesity

Abstract

Purpose of review: Obesity has become a worldwide epidemic that is driving increased morbidity and mortality from thrombotic disorders such as myocardial infarction, stroke, and venous thromboembolism. Effective prevention and treatment of thrombosis in obese patients is limited by an incomplete understanding of the underlying prothrombotic mechanisms and by uncertainties about risks, benefits, and dosing of anticoagulant drugs in this patient population.

Recent findings: This review summarizes our current understanding of established and emerging mechanisms contributing to the obesity-induced prothrombotic state. The mechanistic impact of chronic inflammation and impaired fibrinolysis in mediating obesity-associated thrombosis is highlighted. Recent data demonstrating the aberrant expression of adipokines and microRNAs, which appear to function as key modulators of proinflammatory and prothrombotic pathways in obesity, are also reviewed. Finally, some challenges and new approaches to the prevention and management of thrombotic disorders in obese and overweight patients are discussed.

Summary: Obesity-driven chronic inflammation and impaired fibrinolysis appear to be major effector mechanisms of thrombosis in obesity. The proinflammatory and hypofibrinolytic effects of obesity may be exacerbated by dysregulated expression and secretion of adipokines and microRNAs, which further increase the risk of thrombosis and suggest new potential targets for therapy.

FIGURE 1

Major mechanisms of obesity-associated thrombosis. Obesity promotes chronic inflammation and impaired fibrinolysis, both of which lead to an increased risk of thrombosis. The prothrombotic effects of obesity on inflammatory and antifibrinolytic pathways are modulated, or ‘fine-tuned’ by adipokines and microRNAs. Effector mechanisms include endothelial dysfunction, plaque rupture with exposure of tissue factor, activation of platelets, and delayed clot lysis.

FIGURE 2

Aberrant adipokine expression profile in obesity. Obesity leads to disruption of the balance between prothrombotic adipokines such as leptin, plasminogen activator inhibitor-1 (PAI-1), resistin, and visfatin, and antithrombotic adipokines such as adiponectin and apelin.