Complement activation in thrombotic microangiopathy

The endothelium lining the vascular lumen is continuously exposed to complement from the circulation. When erroneously activated on host cells, complement may generate a deleterious effect on the vascular wall leading to endothelial injury, exposure of the subendothelial matrix and platelet activation. In this review the contribution of complement activation to formation and maintenance of the pathological lesion termed thrombotic microangiopathy (TMA) is discussed. TMA is defined by vessel wall thickening affecting mainly arterioles and capillaries, detachment of the endothelial cell from the basement membrane and intraluminal thrombosis resulting in occlusion of the vessel lumen. The TMA lesion occurs in haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). HUS is further sub-classified as associated with Shiga toxin-producing Escherichia coli (STEC-HUS) or with complement dysregulation (atypical HUS) as well as other less common forms. The contribution of dysregulated complement activation to endothelial injury and platelet aggregation is reviewed as well as specific complement involvement in the development of HUS and TTP.