High prevalence of hereditary thrombotic thrombocytopenic purpura in Central Norway: from clinical observation to evidence.

von Krogh, A S; Quist-Paulsen, P; Waage, A; Langseth, Ø O; Thorstensen, K; Brudevold, R; Tjønnfjord, G E; Largiadèr, Carlo Rodolfo; Lämmle, Bernhard; Kremer Hovinga, Johanna Anna (2016). High prevalence of hereditary thrombotic thrombocytopenic purpura in Central Norway: from clinical observation to evidence. Journal of thrombosis and haemostasis, 14(1), pp. 73-82. Wiley-Blackwell 10.1111/jth.13186

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BACKGROUND Hereditary thrombotic thrombocytopenic purpura (TTP) caused by ADAMTS13 mutations is a rare, but serious condition. The prevalence is unknown, but seems to be high in Norway. OBJECTIVES To identify all patients with hereditary TTP in Central Norway and to investigate the prevalence of hereditary TTP and the population frequencies of two common ADAMTS13 mutations. Patients/Methods Patients were identified in a cross-sectional study within Central Norway Health Region by means of three different search strategies. Frequencies of ADAMTS13 mutations, c.4143_4144dupA and c.3178 C>T (p.R1060W) were investigated in a population-based cohort (500 alleles) and in healthy blood donors (2104 alleles) by taking advantage of the close neighbourhood of the ADAMTS13 and ABO blood group gene loci. The observed prevalence of hereditary TTP was compared to the rates of ADAMTS13 mutation carriers in different geographical regions. RESULTS We identified 11 families with hereditary TTP in Central Norway during the 10-year study period. The prevalence of hereditary TTP in Central Norway was 16.7 x 10(-6) . The most prevalent mutation was c.4143_4144dupA, accounting for two thirds of disease causing alleles among patients and having an allelic frequency of 0.33% in the Central, 0.10% in the Western, and 0.04% in the Southeastern Norwegian population. The allelic frequency of c.3178 C>T (p.R1060W) in the population was even higher (0.3-1%), but this mutation was infrequent among patients, with no homozygous cases. CONCLUSIONS We found a high prevalence of hereditary TTP in Central Norway and an apparently different penetrance of ADAMTS13 mutations. This article is protected by copyright. All rights reserved.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Hämatologie (Erwachsene)
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry

UniBE Contributor:

Largiadèr, Carlo Rodolfo; Lämmle, Bernhard and Kremer Hovinga, Johanna Anna

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1538-7836

Publisher:

Wiley-Blackwell

Language:

English

Submitter:

Ursula Amstutz

Date Deposited:

21 Jan 2016 13:19

Last Modified:

16 Jul 2018 14:19

Publisher DOI:

10.1111/jth.13186

PubMed ID:

26566785

Uncontrolled Keywords:

ADAMTS-13 protein, human; Upshaw-Schulman syndrome; congenital thrombotic thrombocytopenic; purpur mutation; prevalence study

BORIS DOI:

10.7892/boris.74606

URI:

https://boris.unibe.ch/id/eprint/74606

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