لخّصلي

The VWF/ADAMTS13 axis exerts a pivotal role in vascular inflammation and thrombosis [21].This was the "dominant scientific view" until the new concept of "immunothrombosis" was intro- duced [22]. Several studies suggest how thrombosis can be considered a mechanism of intravascular immunity, limiting bacteria from spreading in the bloodstream. On the other hand, systemic inflammation and uncontrolled immunity response (i.e., sepsis) can lead to the extreme "pathological" activation of thrombotic cascade and disseminated intravas- cular coagulation (DIC) [22].Thrombosis, with the recruitment of platelets to the site of vessel's injury, and immune response, with the recruitment of leukocytes in inflamed tissues, have traditionally been considered two distinct pathways.

The VWF/ADAMTS13 axis exerts a pivotal role in vascular inflammation and thrombosis [21]. Thrombosis, with the recruitment of platelets to the site of vessel’s injury, and immune response, with the recruitment of leukocytes in inflamed tissues, have traditionally been considered two distinct pathways. This was the “dominant scientific view” until the new concept of “immunothrombosis” was intro- duced [22]. Several studies suggest how thrombosis can be considered a mechanism of intravascular immunity, limiting bacteria from spreading in the bloodstream. On the other hand, systemic inflammation and uncontrolled immunity response (i.e., sepsis) can lead to the extreme “pathological” activation of thrombotic cascade and disseminated intravas- cular coagulation (DIC) [22]. VWF may represent a possible “connection bridge” between the hemostatic and the inflam- matory pathway (Figures 1 and 2) mediating adhesion and recruitment of both platelets and leukocytes: the network of cell interactions and aggregation is becoming more intriguing [22, 23].
4.1. VWF Secretion in Inflammation. Like C-reactive protein [24–27], VWF is an acute phase reactant [28], and its level increases in inflammatory and metabolic disorders (i.e., glu- cose intolerance, diabetes, and obesity) [29, 30]. In contrast, similar to negative acute phase proteins, ADAMTS13 activity declines in patients with systemic inflammation [31]. As a result, inflammation may potentially activate thrombosis, inducing a marked imbalance between VWF and ADAMTS13. Different mediators of inflammation (cytokines, superoxide anions, histamine, and thrombin) produce an increase in VWF levels through various mech- anisms [32, 33]; for example, IL-8 and TNF-α significantly stimulate the release of UL-VWF by ECs, whereas IL-6 inhibits the UL-VWF cleavage by ADAMTS13. These data suggest that cytokines may potentially affect VWF metabo- lism, and in inflammatory disease, active UL-VWF multimers may accumulate in plasma and induce a prothrombotic state. However, this fascinating hypothesis needs confirma- tory studies.