Livson Sivan, Heikkinen-Eloranta Jenni, Messing Marcel, Lokki A Inkeri, Meri Seppo
Department of Bacteriology and Immunology and Translational Immunology Research Program, Helsinki, Finland; Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Pregnancy Hypertens. 2025 Jun;40:101212. doi: 10.1016/j.preghy.2025.101212. Epub 2025 Apr 29.
Pregnancy-associated Thrombotic Microangiopathy (pTMA) encompasses disorders leading to significant maternal morbidity and mortality and risks to the newborn. The complement system plays a key role in TMA pathogenesis, with pregnancy triggering susceptibility in women. Due to its rarity, timely diagnosis and management of pTMA remain challenging. This study aimed at identifying potential triggers and mechanisms in pregnant women with severe TMA, from an obstetric perspective.
Clinical and molecular data from 11 women with pregnancy-related TMA complications (2012-2022) were analyzed. Blood samples during acute TMA stages were tested for anti-factor H (FH) and anti-ADAMTS13 antibodies using ELISA and Western blotting. Next-generation sequencing and MLPA assays evaluated genetic variants in TMA-related genes.
Clinical records showed similar presentations despite diverse diagnoses, including preeclampsia, HELLP syndrome, AFLP, atypical HUS, and autoimmune TTP, primarily in the third trimester. Eight patients had postpartum hemorrhage (mean blood loss 1312 ml) with normal activated partial thromboplastin times but reduced fibrinogen levels. Genetic findings included two mutations in the C3 gene in one patient, one DGKE mutation, one factor V Leiden mutation, and CFHR3-1 gene deletions (two homozygous, one heterozygous). ADAMTS13 autoantibodies were detected in the TTP case.
The rarity and overlapping criteria of pTMA with other syndromes complicate diagnosis. Early recognition of coagulation abnormalities, hemorrhage, and cardiovascular disorders can help identify at-risk patients. Genetic mutations indicating complement dysregulation suggest that targeted therapies could improve outcomes. Comprehensive diagnostics, timely management, and close follow-up are crucial for optimizing the maternal and fetal health.
Pregnancy-associated thrombotic microangiopathy is a rare life-threatening condition that requires prompt diagnosis and treatment. This study helps obstetricians to identify at-risk patients. In a proportion of cases rare complement gene variants can be identified. The broad spectrum on underlying causes highlights the need for comprehensive diagnostic testing to improve management and outcomes.
妊娠相关血栓性微血管病（pTMA）包括导致孕产妇严重发病和死亡以及对新生儿有风险的疾病。补体系统在TMA发病机制中起关键作用，妊娠会引发女性的易感性。由于其罕见性，pTMA的及时诊断和管理仍然具有挑战性。本研究旨在从产科角度确定重度TMA孕妇的潜在触发因素和机制。
分析了11例妊娠相关TMA并发症患者（2012 - 2022年）的临床和分子数据。在急性TMA阶段采集的血样使用ELISA和蛋白质印迹法检测抗因子H（FH）和抗ADAMTS13抗体。下一代测序和MLPA分析评估TMA相关基因的遗传变异。
临床记录显示，尽管诊断多样，包括先兆子痫、HELLP综合征、急性脂肪肝、非典型溶血尿毒综合征和自身免疫性血栓性血小板减少性紫癜，但主要在孕晚期的表现相似。8例患者发生产后出血（平均失血量1312毫升），活化部分凝血活酶时间正常，但纤维蛋白原水平降低。基因检测结果包括1例患者C3基因的两个突变、1个DGKE突变、1个因子V莱顿突变以及CFHR3 - 1基因缺失（2例纯合子，1例杂合子）。在血栓性血小板减少性紫癜病例中检测到ADAMTS13自身抗体。
pTMA的罕见性以及与其他综合征的重叠标准使诊断复杂化。早期识别凝血异常、出血和心血管疾病有助于识别高危患者。表明补体失调的基因突变提示靶向治疗可能改善预后。全面的诊断、及时的管理和密切的随访对于优化母婴健康至关重要。
妊娠相关血栓性微血管病是一种罕见的危及生命的疾病，需要及时诊断和治疗。本研究有助于产科医生识别高危患者。在一部分病例中可以识别出罕见的补体基因变异。潜在病因的广泛范围凸显了进行全面诊断检测以改善管理和预后的必要性。
