Management and follow-up of pregnancy-onset thrombotic thrombocytopenic purpura: the French experience.

Pregnancy onset-thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening disease which diagnosis and management requires experienced multidisciplinary teams. The mechanisms responsible for ADAMTS13 deficiency leading to pregnancy-onset TTP may be congenital or acquired and studying ADAMTS13 conformation could be of interest. The differential diagnosis between TTP and other pregnancy-associated thrombotic microangiopathies (TMA) is often challenging. Our retrospective multicenter study highlights the significance and the challenges associated with pregnancy-onset TTP and childbirth in terms of diagnosis, obstetric management and follow-up aspects. Among 1174 pregnancy-onset TMA enrolled in the French Registry for TMA from 2000 to 2020, we identified 108 pregnancy-onset TTP: 52 immune-mediated TTP (iTTP, 48.1%), 27 acquired TTP of unidentified mechanism (uTTP, 25%) and 29 congenital TTP (cTTP, 26.9%). Maternal outcome is good (survival rate: 95%) and fetal outcome is linked to the gestational age at the onset of the disease (survival rate: 75.5%). Three distinct entities with different natural histories emerge. Pregnancy-onset iTTP appears similar to idiopathic iTTP, with an open ADAMTS13 conformation, and is marked by a relapse risk independent of subsequent pregnancies. Pregnancy-onset uTTP appears to have a different pathophysiology with an unexpected open ADAMTS13 conformation and a very low relapse risk independent of subsequent pregnancies. Finally, pregnancy-onset cTTP is characterized by the necessity of pregnancy as a systematic and specific trigger and a need for prophylactic plasmatherapy for subsequent pregnancies. This study was registered at www.clinicaltrials.gov (number NCT00426686) and at the Health Authority and the French Ministry of Health (number P051064/PHRC AOM05012).