title: Unexpected frequency of Upshaw-Schulman syndrome in pregnancy-onset thrombotic thrombocytopenic purpura.
abstract: Pregnancy may be complicated by a rare but life-threatening disease called thrombotic thrombocytopenic purpura (TTP). Most cases of TTP are due to an acquired autoimmune or hereditary (Upshaw-Schulman syndrome [USS]) severe deficiency of a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13 (ADAMTS13). In the present study, we performed a cross-sectional analysis of the national registry of the French Reference Center for Thrombotic Microangiopathies from 2000-2010 to identify all women who were pregnant at their initial TTP presentation. Among 592 adulthood-onset TTP patients with a severe ADAMTS13 deficiency, 42 patients with a pregnancy-onset TTP were included. Surprisingly, the proportion of USS patients (n = 10 of 42 patients [24%]; confidence interval, 13%-39%) with pregnancy-onset TTP was much higher than that in adulthood-onset TTP in general (less than 5%) and was mostly related to a cluster of ADAMTS13 variants. In the present study, subsequent pregnancies in USS patients not given prophylaxis were associated with very high TTP relapse and abortion rates, whereas prophylactic plasmatherapy was beneficial for both the mother and the baby. Pregnancy-onset TTP defines a specific subgroup of patients with a strong genetic background. This study was registered at www.clinicaltrials.gov as number NCT00426686 and at the Health Authority, French Ministry of Health, as number P051064.
authors.affiliation: Service d'Hématologie Biologique, Hôpital Antoine Béclère, Assistance Publique-Hôpitaux de Paris (AP-HP), Clamart, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Moatti-Cohen
authors.forename: Céline
authors.initials: C
authors.lastname: Garrec
authors.forename: Martine
authors.initials: M
authors.lastname: Wolf
authors.forename: Pierre
authors.initials: P
authors.lastname: Boisseau
authors.forename: Lionel
authors.initials: L
authors.lastname: Galicier
authors.forename: Elie
authors.initials: E
authors.lastname: Azoulay
authors.forename: Alain
authors.initials: A
authors.lastname: Stepanian
authors.forename: Yahsou
authors.initials: Y
authors.lastname: Delmas
authors.forename: Eric
authors.initials: E
authors.lastname: Rondeau
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bezieau
authors.forename: Paul
authors.initials: P
authors.lastname: Coppo
authors.forename: Agnès
authors.initials: A
authors.lastname: Veyradier
mesh_terms: D051722:ADAM Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000071120:ADAMTS13 Protein; D000328:Adult; D015331:Cohort Studies; D003937:Diagnosis, Differential; D005260:Female; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D030342:Genetic Diseases, Inborn / Q000175:diagnosis / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D011697:Purpura, Thrombotic Thrombocytopenic / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D012042:Registries; D016896:Treatment Outcome
chemical_list: D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human