Novel Insight into Inflammatory Pathways in Acute Pulmonary Embolism in Humans.

Abstract

Accumulating data have shown a pathophysiological association between inflammatory pathways and thrombosis. Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and acute pulmonary embolism (APE), is a significant health burden. It involves not only hemodynamic disturbances due to the emboli occluding the pulmonary arteries, but also platelet activation, endothelial dysfunction, and "firing up" of the inflammatory cascade. In humans, the systemic inflammatory state can also be evaluated using plasma levels of C-reactive protein (CRP) and interleukin (IL)-6, which correlate with venous obstruction, thrombus extension, and clinical VTE complications such as postthrombotic syndrome, recurrent thromboembolism, worse quality of life, and functional impairment. The exaggerated inflammatory state during postthrombotic syndrome aligns with severe alterations in endothelial function, such as activation of intercellular adhesion molecule (ICAM)-1 and E-selectin, as well as vascular proteolysis and fibrinolysis. Moreover, a hypercoagulable state, indicated by higher levels of von Willebrand factor (vWF) and factor VIII, is closely associated with the inflammatory response. We aimed to describe the role of basic inflammatory markers in daily clinical practice as well as the most important cytokines (IL-1β, IL-6, IL-8, tumor necrosis factor-a [TNF-α], growth differentiation factor-15 [GDF-15]). These markers could provide valuable insight into the interplay between thrombosis and inflammation, helping inform better management and treatment strategies.