Repository logo

The ADAMTS13-VWF axis is dysregulated in chronic thromboembolic pulmonary hypertension.

Accepted version

No Thumbnail Available



Change log


Newnham, Michael 
South, Kieron 
Bleda, Marta 
Auger, William R 
Barberà, Joan A 


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.



ADAMTS13 Protein, Adult, Aged, Aged, 80 and over, Biomarkers, Case-Control Studies, Chronic Disease, Endarterectomy, Female, Humans, Hypertension, Pulmonary, Linear Models, Male, Middle Aged, Multivariate Analysis, Pulmonary Embolism, Thrombosis, von Willebrand Factor

Journal Title

Eur Respir J

Conference Name

Journal ISSN


Volume Title



European Respiratory Society (ERS)
MRC (Unknown)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Medical Research Council (MR/K020919/1)
British Heart Foundation (None)