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

Research output: Contribution to journalArticlepeer-review


  • Kieron South
  • Marta Bleda
  • William Auger
  • Joan Barberà
  • Harm Bogaard
  • Katherine Bunclark
  • John Cannon
  • Marion Delcroix
  • Charaka Hadinnapola
  • Luke Howard
  • David Jenkins
  • Eckhard Mayer
  • Choo Ng
  • Christopher Rhodes
  • Nicholas Screaton
  • Karen Sheares
  • Michael Simpson
  • Mark Southwood
  • Li Su
  • Dolores Taboada
  • Matthew Traylor
  • Richard Trembath
  • Sofia Villar
  • Martin Wilkins
  • John Wharton
  • Stefan Gräf
  • Joanna Pepe-Zaba
  • Michael Laffan
  • David Lane
  • Nicholas Morrell
  • Mark Toshner

Colleges, School and Institutes


Chronic thromboembolic pulmonary hypertension (CTEPH) is an important consequence of pulmonary embolism (PE) that is associated with abnormalities in haemostasis. We investigated the ADAMTS13-VWF axis in CTEPH, including its relationship to 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 PE (n=28), idiopathic pulmonary arterial hypertension (n=30) and healthy controls (n=68). CTEPH genetic ABO associations and protein quantitative trait loci were investigated. ADAMTS-VWF axis abnormalities were assessed in CTEPH and healthy control subsets by measuring ADAMTS13 activity, D-dimers and VWF-multimeric size.CTEPH patients had decreased ADAMTS13 (adjusted β (95% CI)=-23.4 (-30.9- -15.1)%, p<0.001) and increased VWF levels (β=+75.5 (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 identify 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.


Original languageEnglish
Article number1801805
JournalEuropean Respiratory Journal
Issue number3
Publication statusPublished - 28 Mar 2019