Management and Follow-Up of Pregnancy-Onset Thrombotic Thrombocytopenic Purpura: The French Experience

Authors: Beranger, Nicolas; Coppo, Paul; Tsatsaris, Vassilis; Boisseau, Pierre; Provot, Francois; Delmas, Yahsou; Poullin, Pascale; Vanhoorelbeke, Karen; Veyradier, Agnes; Joly, Berangere S.

Affiliations: Paris Cite, Hop Lariboisiere, Assistance Publ Hop Paris Nord, Serv Hematol Biol, Paris, France. Univ Paris Cite, Inst Rech St Louis, EA 3518, Paris, France. Sorbonne Univ, Hop St Antoine, Assistance Publ Hop Paris, Serv Hematol,Ctr Reference Microangiopathies Thro, Paris, France. Rech Cordeliers, INSERM, UMRS1138, Paris, France. Univ Paris, Hop Cochin, Assistance Publ Hop Paris Ctr, Matern Port Royal,FHU PREMA, Paris, France. Univ Paris Cite, INSERM, UMR S 1139, Physiopathol & Pharmacotoxicol Placentaire Humain, Paris, France. CHU Nantes, Serv Genet, Nantes, France. [Provot, Francois] CHRU Lille, Serv Nephrol, Lille, France. CHU Bordeaux, Serv Nephrol, Bordeaux, France.] Hop Conception, Assistance Publ Hop Marseille, Serv Hemapherese, Marseille, France. Katholieke Univ Leuven, Lab Thrombosis Res, Campus Kulak Kortrijk, Kortrijk, Belgium.

 

Publication: Blood Adv.2024. 8. 183–193

ABSTRACT: Pregnancy-onset thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening disease of which diagnosis and management requires experienced multidisciplinary teams. The mechanisms responsible for a deficiency in the disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13 (ADAMTS13) leading to pregnancy-onset TTP maybe 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%). Data show that 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 emerged: 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 trial was registered at www. clinicaltrials.gov as #NCT00426686, and at the Health Authority and the French Ministry of Health (P051064/PHRC AOM05012).