[Complement-coagulation crosstalk in immunothrombosis]

Venous thrombosis is initiated by endothelial cell activation triggered by reduced blood flow and venous stasis. Innate immune cells (neutrophils and monocytes) and platelets adhere to activated endothelial cells via P-selectin and von Willebrand factor multimers, respectively. Platelet activation involves integrin activation, P-selectin expression, and the release of ADP, polyphosphates, and soluble complement regulators. Neutrophils bind to the activated platelets and endothelial cells and release neutrophil extracellular traps. Activated monocytes express tissue factor. The interplay of these exacerbated immune and thrombotic events ultimately results in thrombosis, a process now referred to as immunothrombosis. Atypical hemolytic uremic syndrome, aHUS, is a thrombotic microangiopathy caused by uncontrolled activation of the alternative pathway of complement. Genetic analyses of Japanese patients with aHUS predominantly identified a unique gain-of-function C3 variant, p.Ile1157Thr. Patients with this variant showed favorable outcomes despite frequent relapses.