Faculty Collaboration Database

The International Hereditary Thrombotic Thrombocytopenic Purpura Registry: key findings at enrollment until 2017. Haematologica 2019 Oct;104(10):2107-2115

Date

02/23/2019

Pubmed ID

30792199

Pubmed Central ID

PMC6886414

DOI

10.3324/haematol.2019.216796

Scopus ID

2-s2.0-85065445111 (requires institutional sign-in at Scopus site)   93 Citations

Abstract

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.

Author List

van Dorland HA, Taleghani MM, Sakai K, Friedman KD, George JN, Hrachovinova I, Knöbl PN, von Krogh AS, Schneppenheim R, Aebi-Huber I, Bütikofer L, Largiadèr CR, Cermakova Z, Kokame K, Miyata T, Yagi H, Terrell DR, Vesely SK, Matsumoto M, Lämmle B, Fujimura Y, Kremer Hovinga JA, Hereditary TTP Registry

Author

Kenneth D. Friedman MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

ADAMTS13 Protein
Adolescent
Adult
Age of Onset
Aged
Alleles
Child
Child, Preschool
Female
Heterozygote
Homozygote
Humans
Infant
Infant, Newborn
Male
Middle Aged
Mutation
Purpura, Thrombotic Thrombocytopenic