The International Hereditary Thrombotic Thrombocytopenic Purpura Registry: key findings at enrollment until 2017
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The International Hereditary Thrombotic Thrombocytopenic Purpura Registry: key findings at enrollment until 2017. / van Dorland, Hendrika A; Taleghani, Magnus Mansouri; Sakai, Kazuya; Friedman, Kenneth D; George, James N; Hrachovinova, Ingrid; Knöbl, Paul N; von Krogh, Anne Sophie; Schneppenheim, Reinhard; Aebi-Huber, Isabella; Bütikofer, Lukas; Largiadèr, Carlo R; Cermakova, Zuzana; Kokame, Koichi; Miyata, Toshiyuki; Yagi, Hideo; Terrell, Deirdra R; Vesely, Sara K; Matsumoto, Masanori; Lämmle, Bernhard; Fujimura, Yoshihiro; Kremer Hovinga, Johanna A; Hereditary TTP Registry.
in: HAEMATOLOGICA, Jahrgang 104, Nr. 10, 10.2019, S. 2107-2115.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - The International Hereditary Thrombotic Thrombocytopenic Purpura Registry: key findings at enrollment until 2017
AU - van Dorland, Hendrika A
AU - Taleghani, Magnus Mansouri
AU - Sakai, Kazuya
AU - Friedman, Kenneth D
AU - George, James N
AU - Hrachovinova, Ingrid
AU - Knöbl, Paul N
AU - von Krogh, Anne Sophie
AU - Schneppenheim, Reinhard
AU - Aebi-Huber, Isabella
AU - Bütikofer, Lukas
AU - Largiadèr, Carlo R
AU - Cermakova, Zuzana
AU - Kokame, Koichi
AU - Miyata, Toshiyuki
AU - Yagi, Hideo
AU - Terrell, Deirdra R
AU - Vesely, Sara K
AU - Matsumoto, Masanori
AU - Lämmle, Bernhard
AU - Fujimura, Yoshihiro
AU - Kremer Hovinga, Johanna A
AU - Hereditary TTP Registry
N1 - Copyright© 2019 Ferrata Storti Foundation.
PY - 2019/10
Y1 - 2019/10
N2 - Congenital thrombotic thrombocytopenic purpura is an autosomal recessive inherited disease with a clinically heterogeneous course and an incompletely understood genotype-phenotype correlation. In 2006, the Hereditary TTP Registry started recruitment for a study which aimed to improve the understanding of this ultra-rare disease. The objective of this study is to present characteristics of the cohort until the end of 2017 and to explore the relationship between overt disease onset and ADAMTS13 activity with emphasis on the recurring ADAMTS13 c.4143_4144dupA mutation. Diagnosis of congenital thrombotic thrombocytopenic purpura was confirmed by severely deficient ADAMTS13 activity (≤10% of normal) in the absence of a functional inhibitor and the presence of ADAMTS13 mutations on both alleles. By the end of 2017, 123 confirmed patients had been enrolled from Europe (n=55), Asia (n=52, 90% from Japan), the Americas (n=14), and Africa (n=2). First recognized disease manifestation occurred from around birth up to the age of 70 years. Of the 98 different ADAMTS13 mutations detected, c.4143_4144dupA (exon 29; p.Glu1382Argfs*6) was the most frequent mutation, present on 60 of 246 alleles. We found a larger proportion of compound heterozygous than homozygous carriers of ADAMTS13 c.4143_4144dupA with overt disease onset at < 3 months of age (50% vs 37%), despite the fact that ADAMTS13 activity was <1% in 18 of 20 homozygous, but in only 8 of 14 compound heterozygous carriers. An evaluation of overt disease onset in all patients with an available sensitive ADAMTS13 activity assay (n=97) shows that residual ADAMTS13 activity is not the only determinant of age at first disease manifestation. Registered at clinicaltrials.gov identifier NCT01257269.
AB - Congenital thrombotic thrombocytopenic purpura is an autosomal recessive inherited disease with a clinically heterogeneous course and an incompletely understood genotype-phenotype correlation. In 2006, the Hereditary TTP Registry started recruitment for a study which aimed to improve the understanding of this ultra-rare disease. The objective of this study is to present characteristics of the cohort until the end of 2017 and to explore the relationship between overt disease onset and ADAMTS13 activity with emphasis on the recurring ADAMTS13 c.4143_4144dupA mutation. Diagnosis of congenital thrombotic thrombocytopenic purpura was confirmed by severely deficient ADAMTS13 activity (≤10% of normal) in the absence of a functional inhibitor and the presence of ADAMTS13 mutations on both alleles. By the end of 2017, 123 confirmed patients had been enrolled from Europe (n=55), Asia (n=52, 90% from Japan), the Americas (n=14), and Africa (n=2). First recognized disease manifestation occurred from around birth up to the age of 70 years. Of the 98 different ADAMTS13 mutations detected, c.4143_4144dupA (exon 29; p.Glu1382Argfs*6) was the most frequent mutation, present on 60 of 246 alleles. We found a larger proportion of compound heterozygous than homozygous carriers of ADAMTS13 c.4143_4144dupA with overt disease onset at < 3 months of age (50% vs 37%), despite the fact that ADAMTS13 activity was <1% in 18 of 20 homozygous, but in only 8 of 14 compound heterozygous carriers. An evaluation of overt disease onset in all patients with an available sensitive ADAMTS13 activity assay (n=97) shows that residual ADAMTS13 activity is not the only determinant of age at first disease manifestation. Registered at clinicaltrials.gov identifier NCT01257269.
U2 - 10.3324/haematol.2019.216796
DO - 10.3324/haematol.2019.216796
M3 - SCORING: Journal article
C2 - 30792199
VL - 104
SP - 2107
EP - 2115
JO - HAEMATOLOGICA
JF - HAEMATOLOGICA
SN - 0390-6078
IS - 10
ER -