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.
| Original language | English |
|---|---|
| Pages (from-to) | 742-754 |
| Number of pages | 13 |
| Journal | British Journal of Haematology |
| Volume | 144 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2009 Mar |
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Keywords
- ADAMTS13 mutation
- Haemolytic anaemia
- Pregnancy
- Thrombocytopenia
- Upshaw-Schulman syndrome
ASJC Scopus subject areas
- Hematology
Cite this
Pregnancy-induced thrombocytopenia and TTP, and the risk of fetal death, in Upshaw-Schulman syndrome : A series of 15 pregnancies in 9 genotyped patients. / Fujimura, Yoshihiro; Matsumoto, Masanori; Kokame, Koichi; Isonishi, Ayami; Soejima, Kenji; Akiyama, Nobu; Tomiyama, Junji; Natori, Kazuhiko; Kuranishi, Yasunobu; Imamura, Yutaka; Inoue, Nobumasa; Higasa, Satoshi; Seike, Masako; Kozuka, Teruhiko; Hara, Masamichi; Wada, Hideo; Murata, Mitsuru; Ikeda, Yasuo; Miyata, Toshiyuki; George, James N.
In: British Journal of Haematology, Vol. 144, No. 5, 03.2009, p. 742-754.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pregnancy-induced thrombocytopenia and TTP, and the risk of fetal death, in Upshaw-Schulman syndrome
T2 - A series of 15 pregnancies in 9 genotyped patients
AU - Fujimura, Yoshihiro
AU - Matsumoto, Masanori
AU - Kokame, Koichi
AU - Isonishi, Ayami
AU - Soejima, Kenji
AU - Akiyama, Nobu
AU - Tomiyama, Junji
AU - Natori, Kazuhiko
AU - Kuranishi, Yasunobu
AU - Imamura, Yutaka
AU - Inoue, Nobumasa
AU - Higasa, Satoshi
AU - Seike, Masako
AU - Kozuka, Teruhiko
AU - Hara, Masamichi
AU - Wada, Hideo
AU - Murata, Mitsuru
AU - Ikeda, Yasuo
AU - Miyata, Toshiyuki
AU - George, James N.
PY - 2009/3
Y1 - 2009/3
N2 - 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.
AB - 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.
KW - ADAMTS13 mutation
KW - Haemolytic anaemia
KW - Pregnancy
KW - Thrombocytopenia
KW - Upshaw-Schulman syndrome
UR - http://www.scopus.com/inward/record.url?scp=58849165749&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=58849165749&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2141.2008.07515.x
DO - 10.1111/j.1365-2141.2008.07515.x
M3 - Article
C2 - 19055667
AN - SCOPUS:58849165749
VL - 144
SP - 742
EP - 754
JO - British Journal of Haematology
JF - British Journal of Haematology
SN - 0007-1048
IS - 5
ER -