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Title: | The ADAMTS13-VWF axis is dysregulated in chronic thromboembolic pulmonary hypertension |
Author: | Newnham, Michael South, Kieron Bleda, Marta Auger, William R. Barberà i Mir, Joan Albert Bogaard, Harm Bunclark, Katherine Cannon, John E. Delcroix, Marion Hadinnapola, Charaka Howard, Luke S. Jenkins, David Mayer, Eckhard Ng, Choo Rhodes, Christopher J. Screaton, Nicholas Sheares, Karen Simpson, Michael A. Southwood, Mark Su, Li Taboada, Dolores Traylor, Matthew Trembath, Richard C. Villar, Sofia S. Wilkins, Martin R. Wharton, John Gräf, Stefan Pepke-Zaba, Joanna Laffan, Michael Lane, David A. Morrell, Nicholas W. Toshner, Mark |
Keywords: | Coagulació sanguínia Hipertensió pulmonar Blood coagulation Pulmonary hypertension |
Issue Date: | 28-Mar-2019 |
Publisher: | European Respiratory Society |
Abstract: | Chronic thromboembolic pulmonary hypertension (CTEPH) is an important consequence of pulmonary embolism that is associated with abnormalities in haemostasis. We investigated the ADAMTS13-von Willebrand factor (VWF) axis in CTEPH, including its relationship with disease severity, inflammation, ABO groups and ADAMTS13 genetic variants.ADAMTS13 and VWF plasma antigen levels were measured in patients with CTEPH (n=208), chronic thromboembolic disease without pulmonary hypertension (CTED) (n=35), resolved pulmonary embolism (n=28), idiopathic pulmonary arterial hypertension (n=30) and healthy controls (n=68). CTEPH genetic ABO associations and protein quantitative trait loci were investigated. ADAMTS13-VWF axis abnormalities were assessed in CTEPH and healthy control subsets by measuring ADAMTS13 activity, D-dimers and VWF multimeric size.Patients with CTEPH had decreased ADAMTS13 (adjusted β -23.4%, 95% CI -30.9- -15.1%, p<0.001) and increased VWF levels (β +75.5%, 95% CI 44.8-113%, p<0.001) compared to healthy controls. ADAMTS13 levels remained low after reversal of pulmonary hypertension by pulmonary endarterectomy surgery and were equally reduced in CTED. We identified a genetic variant near the ADAMTS13 gene associated with ADAMTS13 protein that accounted for ∼8% of the variation in levels.The ADAMTS13-VWF axis is dysregulated in CTEPH. This is unrelated to pulmonary hypertension, disease severity or markers of systemic inflammation and implicates the ADAMTS13-VWF axis in CTEPH pathobiology. |
Note: | Reproducció del document publicat a: https://doi.org/10.1183/13993003.01805-2018 |
It is part of: | European Respiratory Journal, 2019, vol. 53, num. 3, p. 1801805 |
URI: | http://hdl.handle.net/2445/183789 |
Related resource: | https://doi.org/10.1183/13993003.01805-2018 |
ISSN: | 0903-1936 |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Medicina) |
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