Pregnancy-induced thrombocytopenia and TTP, and the risk of fetal death, in Upshaw-Schulman syndrome: a series of 15 pregnancies in 9 genotyped patients.
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.
Fujimura
Yoshihiro
Y
Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Nara, Japan. malon@naramed-u.ac.jp
Matsumoto
Masanori
M
Kokame
Koichi
K
Isonishi
Ayami
A
Soejima
Kenji
K
Akiyama
Nobu
N
Tomiyama
Junji
J
Natori
Kazuhiko
K
Kuranishi
Yasunobu
Y
Imamura
Yutaka
Y
Inoue
Nobumasa
N
Higasa
Satoshi
S
Seike
Masako
M
Kozuka
Teruhiko
T
Hara
Masamichi
M
Wada
Hideo
H
Murata
Mitsuru
M
Ikeda
Yasuo
Y
Miyata
Toshiyuki
T
George
James N
JN
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
D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human