Ten tips for managing complement-mediated thrombotic microangiopathies (formerly atypical hemolytic uremic syndrome): narrative review.

Abstract

Complement-mediated thrombotic microangiopathies (CM-TMA) are rare and life-threatening disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ damage. These conditions result from dysregulation of the alternative complement pathway, often due to genetic variants or autoantibodies. The clinical spectrum is broad, comprising varied presentations and triggers, including infections, malignancies, and pregnancy-related complications. Advances in understanding the genetic and immunological basis of CM-TMA have improved diagnosis and treatment. Diagnosis requires exclusion of other thrombotic microangiopathies like thrombotic thrombocytopenic purpura and secondary causes, with genetic testing recommended to identify underlying susceptibilities. The introduction of C5 inhibitors has transformed the management of CM-TMA, significantly improving outcomes compared to the pre-2011 era when therapeutic plasma exchange was the primary therapy. Despite these advances, challenges remain in determining the optimal duration of therapy. Prophylactic measures against infections, particularly meningococcal disease, are mandatory for patients receiving C5 inhibitors. This article underscores the need for a personalized, multidisciplinary approach in the diagnosis and management of CM-TMA. Advances in genetics and complement biology have led to improved therapeutic strategies, however ongoing research is essential to address unanswered questions regarding relapse risk, treatment duration, and long-term outcomes.