Supplementary Material for: Differential Diagnosis of Thrombotic Microangiopathy: Overlapping Features of TTP and Complement-Mediated TMA in a Dengue-Infected Patient

Background: Thrombotic microangiopathy (TMA) encompasses a group of rare, life-threatening disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ damage, most commonly affecting the kidneys. Complement-mediated TMA (CM-TMA), a subtype of TMA, is often associated with dysregulation of the complement system due to genetic mutations. Dengue virus has been recognized as a potential trigger of secondary TMA and may precipitate CM-TMA in genetically predisposed individuals.

Case Presentation: We report the case of a 47-year-old woman with a history of thrombotic thrombocytopenic purpura (TTP) who presented with fever, gastrointestinal symptoms, anemia, thrombocytopenia, and acute kidney injury. Dengue infection was confirmed by a positive NS1 antigen. Laboratory and peripheral smear findings indicated TMA. Therapeutic plasma exchange (TPE) was started due to the previous history of TTP, with partial clinical response. ADAMTS13 activity was preserved at 60.7%. Kidney biopsy demonstrated features of TMA. Genetic testing identified a heterozygous pathogenic variant in the CD46 gene, supporting a diagnosis of CM-TMA. Notably, the patient showed sustained clinical improvement without the use of eculizumab.

Conclusion: This case illustrates the diagnostic challenges of TMA in patients with overlapping clinical features and potential infectious triggers. In dengue-endemic regions, the virus should be recognized as a possible precipitating factor for TMA, particularly in individuals harboring complement gene mutations. A multidisciplinary approach—integrating clinical, laboratory, histopathological, and genetic data—is essential for accurate diagnosis and personalized management of TMA syndromes.

背景：血栓性微血管病（Thrombotic microangiopathy, TMA）是一组罕见且危及生命的疾病，以微血管病性溶血性贫血、血小板减少及器官损伤为特征，最常累及肾脏。补体介导型血栓性微血管病（Complement-mediated TMA, CM-TMA）作为TMA的一个亚型，常因遗传突变导致补体系统失调而发病。登革病毒已被认为是继发性TMA的潜在诱因，可能在遗传易感个体中诱发CM-TMA。病例介绍：我们报告1例47岁女性患者，既往有血栓性血小板减少性紫癜（Thrombotic thrombocytopenic purpura, TTP）病史，此次因发热、胃肠道症状、贫血、血小板减少及急性肾损伤就诊。NS1抗原检测阳性证实为登革病毒感染。实验室检查及外周血涂片结果符合TMA表现。鉴于患者既往TTP病史，予以治疗性血浆置换（Therapeutic plasma exchange, TPE）治疗，临床反应部分缓解。ADAMTS13活性维持在60.7%。肾活检显示TMA特征性改变。基因检测发现CD46基因存在杂合致病性变异，支持CM-TMA的诊断。值得注意的是，患者未使用依库珠单抗（eculizumab）即获得持续临床改善。结论：本病例凸显了TMA在临床特征重叠且存在潜在感染诱因患者中的诊断难点。在登革热流行地区，应将该病毒视为TMA的潜在诱发因素，尤其是在携带补体系统基因突变的个体中。整合临床、实验室、组织病理学及遗传学数据的多学科诊疗模式，对于TMA综合征的精准诊断与个体化管理至关重要。