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Understanding this phenomenon in the clinical setting has been limited by incomplete data and a lack of uniform diagnostic and reporting criteria. While apparently rare based on available information, AAV-associated TMA\/aHUS can pose a substantial risk to patients including one published fatality. Reported cases were originally limited to pediatric Duchenne muscular dystrophy patients receiving micro- or mini-dystrophin transgenes via AAV9 but have subsequently been reported in both pediatric and adult patients across a range of disorders, transgenes, promoters, and AAV capsid types. This article provides an introduction to the complement system, TMA and aHUS, and anticomplement therapies, then presents clinical reviews of AAV-associated TMA\/aHUS cases that have been reported publicly. Finally, exploration of risk factors and current and future mitigation approaches are discussed.<\/jats:p>","DOI":"10.1089\/hum.2024.156","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T10:00:41Z","timestamp":1737021641000},"page":"64-76","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":32,"title":["Thrombotic Microangiopathy Associated with Systemic Adeno-Associated Virus Gene Transfer: Review of Reported Cases"],"prefix":"10.1177","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0888-271X","authenticated-orcid":false,"given":"Genevieve A.","family":"Laforet","sequence":"first","affiliation":[{"name":"BridgeBio Gene Therapy, Palo Alto, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,2,10]]},"reference":[{"key":"e_1_3_5_2_2","unstructured":"FDA News Release. 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