title: Incidence of obstetrical thrombotic thrombocytopenic purpura in a retrospective study within thrombocytopenic pregnant women. A difficult diagnosis and a treatable disease.
abstract: BACKGROUND
  Thrombotic thrombocytopenic Purpura (TTP) defined as ADAMTS-13 (A Disintegrin And Metalloprotease with ThromboSpondin type 1 domain 13) activity <10 % is a rare aetiology of thrombocytopenia during pregnancy, although the precise incidence is unknown. During pregnancy, the diagnosis of TTP is crucial as it has high feto-maternal morbidity-mortality and requires urgent plasma exchange. The purpose of this study was to assess the incidence of TTP retrospectively and to describe case presentations and follow-up.
  
  
  METHODS
  A monocentric retrospective study (2008-2009) was conducted among pregnant women followed in a tertiary care obstetrical unit who experienced at least one episode of severe thrombocytopenia (platelets ≤75 G/L) during 2008 and 2009. In cases of uncertain aetiology of thrombocytopenia, ADAMTS-13 activity was assessed by the full length technique.
  
  
  RESULTS
  Among 8,908 deliveries over the 2 year period, 79 women had a platelet count nadir ≤75 G/L. Eighteen had a known aetiology of thrombocytopenia and 11 were lost to follow-up. Among 50 remaining patients, ADAMTS-13 activity was undetectable (<5 %) in 4, consistent with the diagnosis of TTP. Platelet count spontaneously normalized in 3 patients after delivery. None presented focal cerebral involvement. Three of the four, who were primipara patients, had a sustained severe deficiency in the absence of anti-ADAMTS-13 antibodies, and ADAMTS-13 gene sequencing indicated a constitutive deficiency. The fourth, a multipara patient, had an acquired, auto-immune TTP. Placental pathology in the three primipara patients showed severe and non-specific ischemic lesions. Two patients lost their babies shortly after birth. In subsequent pregnancies in these two patients, prophylactic plasma infusion initiated early with increasing volume throughout pregnancy prevented TTP relapse, improved placental pathology, and led to normal delivery.
  
  
  CONCLUSIONS
  The prevalence of TTP among thrombocytopenic pregnant women is high, up to 5 % in a tertiary unit. Platelet count normalization after delivery does not eliminate TTP. Clinicians should be aware of TTP during pregnancy, and, even if assessed retrospectively, ADAMTS-13 assessment is of particular importance for identifying patients with congenital TTP. In these patients, preventive plasma infusion and/or exchange can dramatically improve foetal prognosis, resulting in successful childbirth.
authors.affiliation: Service de Néphrologie Transplantation Dialyse, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France. yahsou.delmas@chu-bordeaux.fr.|Centre de Compétence des Microangiopathies Thrombotiques, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France. yahsou.delmas@chu-bordeaux.fr.
authors.forename: Yahsou
authors.initials: Y
authors.lastname: Delmas
authors.affiliation: Service de Néphrologie Transplantation Dialyse, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France. helou@clinique-delay.fr.|Université Bordeaux Segalen, Bordeaux, France. helou@clinique-delay.fr.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Helou
authors.affiliation: Centre de Compétence des Microangiopathies Thrombotiques, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France. pierre.chabanier@chu-bordeaux.fr.|Pôle Gynécologie-Obstétrique-et Médecine Foetale, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France. pierre.chabanier@chu-bordeaux.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Chabanier
authors.affiliation: Centre de Compétence des Microangiopathies Thrombotiques, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France. anne.ryman@chu-bordeaux.fr.|Service d'Hémostase Spécialisée, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France. anne.ryman@chu-bordeaux.fr.
authors.forename: Anne
authors.initials: A
authors.lastname: Ryman
authors.affiliation: Service d'Anatomie Pathologique, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France. fanny.pelluard@chu-bordeaux.fr.|Université Bordeaux Segalen, Bordeaux, France. fanny.pelluard@chu-bordeaux.fr.
authors.forename: Fanny
authors.initials: F
authors.lastname: Pelluard
authors.affiliation: Service d'Anatomie Pathologique, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France. dominique.carles@u-bordeaux.fr.|Université Bordeaux Segalen, Bordeaux, France. dominique.carles@u-bordeaux.fr.
authors.forename: Dominique
authors.initials: D
authors.lastname: Carles
authors.affiliation: Service de Génétique Médicale, Centre Hospitalier Universitaire de Nantes Hôtel Dieu, Nantes, France. pierre.boisseau@chu-nantes.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Boisseau
authors.affiliation: Service d'hématologie, Centre Hospitalier Universitaire de Lariboisière, Assistance Publique Hôpitaux de Paris, Université Paris 7 Denis Diderot, Paris, France. agnes.veyradier@lrb.aphp.fr.|Centre de Référence des Microangiopathies Thrombotiques, Paris, France. agnes.veyradier@lrb.aphp.fr.
authors.forename: Agnès
authors.initials: A
authors.lastname: Veyradier
authors.affiliation: Pôle Gynécologie-Obstétrique-et Médecine Foetale, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France. jacques.horovitz@chu-bordeaux.fr.|Université Bordeaux Segalen, Bordeaux, France. jacques.horovitz@chu-bordeaux.fr.
authors.forename: Jacques
authors.initials: J
authors.lastname: Horovitz
authors.affiliation: Centre de Référence des Microangiopathies Thrombotiques, Paris, France. paul.coppo@sat.aphp.fr.|Service d'Hématologie Hôpital Saint Antoine, Assistance Publique Hôpitaux de Paris, Paris, France. paul.coppo@sat.aphp.fr.|Université Pierre et Marie Curie (UPMC), Univ Paris 6, Paris, France. paul.coppo@sat.aphp.fr.
authors.forename: Paul
authors.initials: P
authors.lastname: Coppo
authors.affiliation: Service de Néphrologie Transplantation Dialyse, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France. christian.combe@chu-bordeaux.fr.|Centre de Compétence des Microangiopathies Thrombotiques, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France. christian.combe@chu-bordeaux.fr.|Université Bordeaux Segalen, Bordeaux, France. christian.combe@chu-bordeaux.fr.
authors.forename: Christian
authors.initials: C
authors.lastname: Combe
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors / Q000097:blood; D000071120:ADAMTS13 Protein; D000328:Adult; D005260:Female; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D010298:Parity; D066087:Perinatal Death; D010920:Placenta / Q000473:pathology; D010956:Plasmapheresis; D010976:Platelet Count; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000097:blood / Q000453:epidemiology* / Q000628:therapy; D011256:Pregnancy Outcome; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood / Q000453:epidemiology* / Q000628:therapy; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human