Premium
Von Willebrand factor and ADAMTS13 impact on the outcome of Staphylococcus aureus sepsis
Author(s) -
Peetermans Marijke,
Meyers Severien,
Liesenborghs Laurens,
Vanhoorelbeke Karen,
De Meyer Simon F.,
Vandenbriele Christophe,
Lox Marleen,
Hoylaerts Marc F.,
Martinod Kimberly,
Jacquemin Marc,
Vanassche Thomas,
Verhamme Peter
Publication year - 2020
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.14686
Subject(s) - adamts13 , von willebrand factor , sepsis , staphylococcus aureus , medicine , immunology , bacteremia , disseminated intravascular coagulation , platelet , gastroenterology , microbiology and biotechnology , biology , bacteria , genetics , antibiotics
Background Previous clinical evidence correlates levels of von Willebrand factor (VWF) and its cleaving protease ADAMTS13 with outcome in septic patients. No previous studies addressed if VWF and ADAMTS13 affected the outcome of Staphylococcus aureus sepsis. Objectives We studied the role of VWF and ADAMTS13 in S. aureus sepsis both in patients and in mice. Methods VWF levels and ADAMTS13 activity levels were measured in plasma samples from 89 S. aureus bacteremia patients by chemiluminescent assays and were correlated with clinical sepsis outcome parameters. In wild‐type mice and mice deficient in VWF and ADAMTS13, we investigated the outcome of S. aureus sepsis and quantified bacterial clearance and organ microthrombi. Results In patients with S. aureus bloodstream infections, high VWF levels and low ADAMTS13 activity levels correlated with disease severity and with parameters of inflammation and disseminated intravascular coagulation. In septic mice, VWF deficiency attenuated mortality, whereas ADAMTS13 deficiency increased mortality. Bacterial clearance was enhanced in VWF‐deficient mice. The differences in mortality for the studied genotypes were associated with differential loads of organ microthrombi in both liver and kidneys. Conclusions In conclusion, this study reports the consistent relation of VWF, ADAMTS13 and their ratio to disease severity in patients and mice with S. aureus sepsis. Targeting VWF multimers and/or the relative ADAMTS13 deficiency that occurs in sepsis should be explored as a potential new therapeutic target in S. aureus endovascular infections.