Fig. 1.

The role of complement in thrombotic microangiopathies. A mutation or autoantibody resulting in complement dysregulation predisposes to complement-mediated aHUS. Complement-mediated aHUS frequently only manifests upon exposure to an environmental trigger, which can include other causes of TMA. In some TMAs, a high proportion of individuals carry a mutation (e.g., pregnancy associated aHUS, ~ 70%, and de novo post-transplant TMA, ~ 30%) but in others the incidence of mutations is unknown or low (e.g., STEC-HUS). In other TMAs, complement activation may be seen in vivo but whether it plays a role as a disease modifier or is simply a bystander is yet to be clarified