Hamostaseologie 2020; 40(S 01): S33-S52
DOI: 10.1055/s-0040-1721573
III. Günter Landbeck Excellence Award

The International Hereditary Thrombotic Thrombocytopenic Purpura Registry: Key findings at Enrolment until 2017

Hendrika A. van Dorland
1   Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, Bern, Switzerland
2   Department for BioMedical Research, University of Bern, Bern, Switzerland
,
Magnus Mansouri Taleghani
1   Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, Bern, Switzerland
,
Kazuya Sakai
3   Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Japan
,
Kenneth D. Friedman
4   Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
,
James N. George
5   Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
,
Ingrid Hrachovinova
6   NRL for Hemostasis, Institute of Hematology and Blood Transfusion, Prague, Czech Republic
,
Paul N. Knöbl
7   Division of Hematology and Hemostasis, Department of Medicine 1, Medical University of Vienna, Austria
,
Anne Sophie von Krogh
8   Department of Hematology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
,
Reinhard Schneppenheim
9   Department of Pediatric Hematology and Oncology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
,
Isabella Aebi-Huber
1   Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, Bern, Switzerland
2   Department for BioMedical Research, University of Bern, Bern, Switzerland
,
Lukas Bütikofer
10   CTU Bern, University of Bern, Bern, Switzerland
,
Carlo R. Largiadèr
11   University Institute of Clinical Chemistry, Inselspital, Bern University Hospital, Bern, Switzerland
,
Zuzana Cermakova
12   Blood Center, University Hospital Ostrava, Ostrava, Czech Republic
,
Koichi Kokame
13   Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center, Suita, Japan
,
Toshiyuki Miyata
13   Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center, Suita, Japan
14   Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center Suita Japan
,
Hideo Yagi
3   Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Japan
15   Department of Hematology, Nara Prefecture General Medical Center, Nara, Japan
,
Deirdra R. Terrell
5   Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
,
Sara K. Vesely
5   Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
,
Masanori Matsumoto
3   Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Japan
,
Bernhard Lämmle
1   Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, Bern, Switzerland
16   Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany
,
Yoshihiro Fujimura
3   Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Japan
17   Japanese Red Cross Kinki Block Blood Center, Ibaraki, Osaka, Japan
,
Johanna A. Kremer Hovinga
1   Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, Bern, Switzerland
2   Department for BioMedical Research, University of Bern, Bern, Switzerland
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    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 with the purpose of improving 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 ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity with emphasis on the recurring ADAMTS-13 c.4143_4144dupA mutation. Diagnosis of congenital thrombotic thrombocytopenic purpura was confirmed by severely deficient ADAMTS-13 activity (<10% of normal) in the absence of a functional inhibitor and the presence of ADAMTS-13 mutations on both alleles. By the end of 2017, a total of 123 confirmed patients were enrolled from Europe (55), Asia (52, 90% from Japan), America (14), and Africa (2). First recognized disease manifestation occurred around birth up to the age of 70 years. Of the 97 different ADAMTS-13 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 ADAMTS-13 c.4143_4144dupA with overt disease onset at <3 months of age (50 vs. 37%), despite the fact that ADAMTS-13 activity was <1% in 18 of 20 homozygous carriers, but in only 8 of 14 compound heterozygous carriers. Evaluating overt disease onset in all patients with a sensitive ADAMTS-13 activity determination available (n = 97), it becomes evident that residual ADAMTS-13 activity is not the only determinant of the age at first disease manifestation (clinicaltrials.gov identifier NCT01257269).

    Haematologica 2019 Feb 21. pii: haematol.2019.216796. doi: 10.3324/haematol.2019.216796. [Epub ahead of print]


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    No conflict of interest has been declared by the author(s).

    Publication History

    Article published online:
    13 November 2020

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