Schematic presentation of the main links between the complement and coagulation systems and platelets in formation of microthrombi in aHUS. Complement activation leads to release of the C5a peptide, inducing tissue factor activity on endothelial cells leading to a procoagulative state of the endothelium. Activation of the coagulation cascade leads to generation of active thrombin that is able to cleave not only fibrinogen but also complement C5, which thereby enables coagulation-enhanced complement activation. Formation of membrane attack complexes on endothelial cells and platelets can cause endothelial cell damage and platelet activation. Finally, activation of the coagulation system leads to platelet activation via various mechanisms. Together, the coagulation system and platelet activation/aggregation lead to formation of microthrombi. The importance of complement in this process in aHUS is clearly demonstrated by rapid inhibition of microvascular thrombosis by therapeutic complement inhibition.