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

Research output: Contribution to journalArticle

Authors

  • 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

Abstract

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.

Details

Original languageEnglish
Article number1801805
JournalEuropean Respiratory Journal
Volume53
Issue number3
Publication statusPublished - 28 Mar 2019