The ADAMTS13–VWF axis is dysregulated in chronic thromboembolic pulmonary hypertension. Issue 3 (28th March 2019)

• Record Type: Journal Article
• Authors: Newnham, Michael; South, Kieron; Bleda, Marta; Auger, William R.; Barberà, Joan A.; 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;
• Is Part Of: European respiratory journal. Volume 53:Issue 3(2019)
• Publication Date: 2019-03-28
• Subjects: Respiratory organs -- Diseases -- Periodicals; Respiration -- Periodicals; 616.2
• DOI: 10.1183/13993003.01805-2018
• Languages: English
• ISSNs: 0903-1936

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. The ADAMTS-13–VWF axis is dysregulated in chronic thromboembolism with and without pulmonary hypertension and is implicated in the pathogenesis http://ow.ly/J9SC30nh5T0