title: Pregnancy-induced thrombocytopenia and TTP, and the risk of fetal death, in Upshaw-Schulman syndrome: a series of 15 pregnancies in 9 genotyped patients.
abstract: Upshaw-Schulman syndrome (USS) is a congenital thrombotic thrombocytopenic purpura (TTP) due to mutations in the gene that encodes for ADAMTS13 (ADAMTS13), but its clinical signs may be mild or absent during childhood. We have identified 37 patients with USS (24 females, 13 males) belonging to 32 families. The nine women from six families who were diagnosed during their first pregnancy are the focus of this report. Six of the nine women had episodes of thrombocytopenia during childhood misdiagnosed as idiopathic thrombocytopenic purpura. Thrombocytopenia occurred during the second-third trimesters in each of their 15 pregnancies, with 16 babies (one twin pregnancy), often followed by TTP. Of 15 pregnancies, eight babies were stillborn or died soon after birth, and the remaining seven were all premature except one, who was born naturally following plasma infusions to the mother that had started at 8 weeks' gestation. All nine USS women had severely deficient ADAMTS13 activity. ADAMTS13 analyses demonstrated that eight women were compound heterozygotes of Y304C/G525D (2 siblings), R125VfsX6/Q1302X (2 siblings), R193W/R349C (2 siblings), I178T/Q929X, and R193W/A606P; one woman was homozygous for R193W. Only the R193W mutation has been previously reported. These observations emphasize the importance of measuring ADAMTS13 activity in the evaluation of thrombocytopenia during childhood and pregnancy.
authors.affiliation: Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Nara, Japan. malon@naramed-u.ac.jp
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujimura
authors.forename: Masanori
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Koichi
authors.initials: K
authors.lastname: Kokame
authors.forename: Ayami
authors.initials: A
authors.lastname: Isonishi
authors.forename: Kenji
authors.initials: K
authors.lastname: Soejima
authors.forename: Nobu
authors.initials: N
authors.lastname: Akiyama
authors.forename: Junji
authors.initials: J
authors.lastname: Tomiyama
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Natori
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Kuranishi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Imamura
authors.forename: Nobumasa
authors.initials: N
authors.lastname: Inoue
authors.forename: Satoshi
authors.initials: S
authors.lastname: Higasa
authors.forename: Masako
authors.initials: M
authors.lastname: Seike
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Kozuka
authors.forename: Masamichi
authors.initials: M
authors.lastname: Hara
authors.forename: Hideo
authors.initials: H
authors.lastname: Wada
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Murata
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miyata
authors.forename: James N
authors.initials: JN
authors.lastname: George
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors / Q000097:blood / Q000235:genetics; D000071120:ADAMTS13 Protein; D000328:Adult; D015153:Blotting, Western; D004252:DNA Mutational Analysis; D005260:Female; D005313:Fetal Death; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010375:Pedigree; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000235:genetics* / Q000401:mortality; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D011697:Purpura, Thrombotic Thrombocytopenic / Q000151:congenital* / Q000235:genetics* / Q000401:mortality; D012306:Risk
chemical_list: D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human