The International Hereditary Thrombotic Thrombocytopenic Purpura Registry: key findings at enrollment until 2017
Hendrika A. van Dorland,
Magnus Mansouri Taleghani,
Kazuya Sakai,
Kenneth D. Friedman,
James N. George,
Ingrid Hrachovinova,
Paul N. Knöbl,
Anne Sophie von Krogh,
Reinhard Schneppenheim,
Isabella Aebi-Huber,
Lukas Bütikofer,
Carlo R. Largiadèr,
Zuzana Cermakova,
Koichi Kokame,
Toshiyuki Miyata,
Hideo Yagi,
Deirdra R. Terrell,
Sara K. Vesely,
Masanori Matsumoto,
Bernhard Lämmle,
Yoshihiro Fujimura,
Johanna A. Kremer Hovinga
Affiliations
Hendrika A. van Dorland
Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, Bern, Switzerland;Department for BioMedical Research, University of Bern, Bern, Switzerland
Magnus Mansouri Taleghani
Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, Bern, Switzerland
Kazuya Sakai
Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Japan
Kenneth D. Friedman
Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USA
James N. George
Department of Biostatistics Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
Ingrid Hrachovinova
NRL for Hemostasis, Institute of Hematology and Blood Transfusion, Prague, Czech Republic
Paul N. Knöbl
Division of Hematology and Hemostasis, Department of Medicine 1, Medical University of Vienna, Austria
Anne Sophie von Krogh
Department of Hematology, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
Reinhard Schneppenheim
Department of Paediatric Haematology and Oncology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
Isabella Aebi-Huber
Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, Bern, Switzerland;Department for BioMedical Research, University of Bern, Bern, Switzerland
Lukas Bütikofer
CTU Bern, University of Bern, Bern, Switzerland
Carlo R. Largiadèr
University Institute of Clinical Chemistry, Inselspital, Bern University Hospital, Bern, Switzerland
Zuzana Cermakova
Blood Center, University Hospital Ostrava, Ostrava, Czech Republic
Koichi Kokame
Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center, Suita, Japan
Toshiyuki Miyata
Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center, Suita, Japan;Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan
Hideo Yagi
Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Japan;Department of Hematology, Nara Prefecture General Medical Center, Nara, Japan
Deirdra R. Terrell
Department of Biostatistics Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
Sara K. Vesely
Department of Biostatistics Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
Masanori Matsumoto
Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Japan
Bernhard Lämmle
Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, Bern, Switzerland;Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany
Yoshihiro Fujimura
Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Japan;Japanese Red Cross Kinki Block Blood Center, Ibaraki, Osaka, Japan
Johanna A. Kremer Hovinga
Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, Bern, Switzerland;Department for BioMedical Research, University of Bern, Bern, Switzerland
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
