Complement Blockade Is a Promising Therapeutic Approach in a Subset of Critically Ill Adult Patients with Complement-Mediated Hemolytic Uremic Syndromes

Abstract

Thrombotic microangiopathy (TMA) gathers consumptive thrombocytopenia, mechanical haemolytic anemia, and organ damage. Hemolytic uremic syndromes (HUS) are historically classi-fied as primary or secondary to another disease once thrombotic thrombocytopenic purpura (TTP), Shiga-toxin HUS, and cobalamin C-related HUS have been ruled out. Complement genetics studies reinforced the link between complement dysregulation and primary HUS, contributing to reclassifying some pregnancy-and/or post-partum-associated HUS and to revealing complement involve-ment in severe and/or refractory hypertensive emergencies. By contrast, no firm evidence allows a plausible association to be drawn between complement dysregulation and Shiga-toxin HUS or other secondary HUS. Nevertheless, rare complement gene variants are prevalent in healthy individuals, thus providing an indication that an investigation into complement dysregulation should be care-fully balanced and that the results should be cautiously interpreted with the help of a trained ge-neticist. Several authors have suggested reclassifying HUS in two entities, regardless of they are complement-mediated or not, since the use of eculizumab, an anti-C5 antibody, dramatically lowers the proportion of patients who die or suffer from end-stage renal disease within the year following diagnosis. Safety and the ideal timing of eculizumab discontinuation is currently under investiga-tion, and the long-term consequences of HUS should be closely monitored over time once patients exit emergency departments.