Sartori Pacini Gabriel, Eick Renato George, Schuchmann Renata Asnis, Fernandes Mário Sergio, da Luz Lucas Gobetti, Balestrin Illan George, Pêgas Karla Lais, Kalil Milton, Lutzky Maurício
Division of Nephrology, Hospital Moinhos de Vento de Porto Alegre, Porto Alegre, Brazil.
Division of Nephrology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
Nephron. 2025 Aug 2:1-6. doi: 10.1159/000547796.
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.
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 was started due to 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 the diagnosis of CM-TMA. Notably, the patient showed sustained clinical improvement without the use of eculizumab.
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.
血栓性微血管病(TMA)是一组罕见的、危及生命的疾病,其特征为微血管病性溶血性贫血、血小板减少和器官损害,最常累及肾脏。补体介导的TMA(CM-TMA)是TMA的一种亚型,常因基因突变导致补体系统失调。登革病毒已被认为是继发性TMA的潜在触发因素,可能在具有遗传易感性的个体中引发CM-TMA。
我们报告一例47岁有血栓性血小板减少性紫癜(TTP)病史的女性患者,其出现发热、胃肠道症状、贫血、血小板减少和急性肾损伤。NS1抗原阳性证实登革热感染。实验室检查和外周血涂片结果提示TMA。由于既往有TTP病史,开始进行治疗性血浆置换,临床症状有部分改善。ADAMTS13活性维持在60.7%。肾脏活检显示TMA特征。基因检测在CD46基因中发现一个杂合致病性变异,支持CM-TMA的诊断。值得注意的是,该患者未使用依库珠单抗病情持续改善。
本病例说明了具有重叠临床特征和潜在感染触发因素的患者中TMA的诊断挑战。在登革热流行地区,应认识到该病毒可能是TMA的诱发因素,特别是在携带补体基因突变的个体中。采用多学科方法——整合临床、实验室、组织病理学和基因数据——对于TMA综合征的准确诊断和个性化管理至关重要。