Coagulation and endothelial dysfunction associated with NAFLD: Current status and therapeutic implications
image: CRP, C-reactive protein; F, factor; IL-6, interleukin 6; NO, nitric oxide; PAI-1, plasminogen activator inhibitor-1; ROS, reactive oxygen species; TNF-α, tumor necrosis factor-α; vWF, von Willebrand factor.
Credit: By Doris Ogresta & Lucija Virovic-Jukic
Hemostasis, the process to prevent and stop bleeding, involves three phases: formation of a platelet plug, activation of the coagulation cascade resulting in fibrin clot formation, and fibrinolysis. In NAFLD, there's a shift towards a procoagulant state. This shift is influenced by factors such as obesity, insulin resistance, chronic inflammation, and an imbalance of adipokines. The progression of NAFLD severity is associated with a corresponding increase in hemostatic abnormalities, indicating a higher risk of thrombotic events.
There is evidence that endothelial vascular dysfunction, platelet abnormalities, and alterations in factors involved in the coagulation cascade and fibrinolysis may all contribute to a prothrombotic state in patients with NAFLD. The alterations could be triggered by low-grade chronic inflammation. Involvement of multiple organs and organ systems results in high morbidity and mortality of NAFLD patients.
Endothelial cells, crucial for maintaining vascular health, are affected in NAFLD. They regulate blood flow, vascular tone, and balance prothrombotic and anticoagulant factors. Insulin resistance, a core aspect of NAFLD, impairs endothelial nitric oxide synthase (eNOS) function, reducing nitric oxide production, crucial for endothelial function. This leads to endothelial dysfunction (ED), connecting NAFLD to cardiovascular diseases. Intrahepatic endothelial dysfunction in NAFLD, crucial for liver pathology, also contributes to systemic cardiovascular risk, marking NAFLD as an independent risk factor for cardiovascular diseases.
We have just started to scratch the surface of numerous possibilities revealed by the role of platelets, ED, and changes in the coagulation system and liver damage in terms of treatment, and management of NAFLD. As some data suggest that hypercoagulability is associated with NAFLD, it would be prudent to estimate benefits from anticoagulant and/or antiaggregation therapy in patients with NAFLD.