How I treat thrombotic microangiopathy in the setting of triggers

Abstract Complement-mediated thrombotic microangiopathy can be difficult to recognize when it presents in the setting of an apparent clinical trigger, such as pregnancy, severe hypertension, or kidney transplantation. These conditions can each cause endothelial injury directly but may also unmask complement dysregulation in susceptible individuals. In these situations, the critical question is not whether a trigger exists but whether it fully explains the syndrome and whether urgent complement blockade is warranted to prevent irreversible kidney injury. In this How I Treat article, we use 3 real-world cases to illustrate how we approach this decision in practice. We emphasize the bedside features that most influence our threshold to treat, including the pattern and severity of kidney injury, tempo of disease progression, and lack of improvement with supportive or trigger-directed care. We also address the interpretation of complement genetic findings, pregnancy- and transplant-specific risk stratification, and the individualization of treatment duration. Functional assays can support mechanistic assessment in selected cases but remain an adjunct to diagnosis and should not drive management decisions.