TY - JOUR
T1 - Consumptive coagulopathy is associated with a disturbed host response in patients with sepsis
AU - van Vught, Lonneke A.
AU - Uhel, Fabrice
AU - Ding, Chao
AU - van‘t Veer, Cees
AU - Scicluna, Brendon P.
AU - Peters-Sengers, Hessel
AU - Klein Klouwenberg, Peter M. C.
AU - Nürnberg, Peter
AU - Cremer, Olaf L.
AU - the MARS consortium
AU - Schultz, Marcus J.
AU - van der Poll, Tom
AU - de Beer, Friso M.
AU - Bos, Lieuwe D. J.
AU - Glas, Gerie J.
AU - Hoogendijk, Arie J.
AU - van Hooijdonk, Roosmarijn T. M.
AU - Horn, Janneke
AU - Huson, Mischa A.
AU - Schouten, Laura R. A.
AU - Scicluna, Brendon P.
AU - Straat, Marleen
AU - van Vught, Lonneke A.
AU - Wieske, Luuk
AU - Wiewel, Maryse A.
AU - Witteveen, Esther
AU - Bonten, Marc J. M.
AU - Cremer, Olaf M.
AU - Ong, David S. Y.
AU - Frencken, Jos F.
AU - Klein Klouwenberg, Peter M. C.
AU - Koster-Brouwer, Maria E.
AU - van de Groep, Kirsten
AU - Verboom, Diana M.
N1 - Funding Information:
The MARS project was supported by the Center for Translational Molecular Medicine (http://www.ctmm.nl), project MARS (grant 04I-201). Chao Ding was supported by the Chinese Scholarship Council (CSC). Members of the MARS consortium: Amsterdam University Medical Centers, Academic Medical Center, University of Amsterdam, the Netherlands: Friso M. de Beer, Lieuwe D. J. Bos, Gerie J. Glas, Arie J. Hoogendijk, Roosmarijn T. M. van Hooijdonk, Janneke Horn, Mischa A. Huson, Laura R. A. Schouten, Marcus J. Schultz, Brendon P. Scicluna, Marleen Straat, Lonneke A. van Vught, Luuk Wieske, Maryse A. Wiewel, Esther Witteveen. University Medical Center Utrecht, Utrecht, the Netherlands: Marc J.M. Bonten, Olaf M. Cremer, David S.Y. Ong, Jos F. Frencken, Peter M.C. Klein Klouwenberg, Maria E. Koster-Brouwer, Kirsten van de Groep, Diana M. Verboom.
Funding Information:
The MARS project was supported by the Center for Translational Molecular Medicine ( http://www.ctmm.nl ), project MARS (grant 04I‐201). Chao Ding was supported by the Chinese Scholarship Council (CSC).
Publisher Copyright:
© 2021 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/4/1
Y1 - 2021/4/1
N2 - Background: A prolonged prothrombin time (PT) is a common feature in sepsis indicating consumptive coagulopathy. Objectives: To determine the association between a prolonged PT and aberrations in other host response mechanisms in sepsis. Methods: Patients admitted to the intensive care unit with sepsis were divided in quartiles according to the highest PT value measured within 24 h after admission. The host response was evaluated by measuring 19 plasma biomarkers reflecting pathways implicated in sepsis pathogenesis and by blood leukocyte gene expression profiling. Measurements and Main Results: Of 1524 admissions for sepsis, 386 (25.3%) involved patients with a normal PT (≤12.7 s); the remaining quartiles entailed 379 (24.9%) patients with a slightly prolonged PT (12.8 ≤ PT ≤ 15.0 s), 383 (25.1%) with an intermediately prolonged PT (15.1 ≤ PT ≤ 17.2 s), and 376 (24.7%) with an extremely prolonged PT (≥17.3 s). While patients with an extremely prolonged PT showed an increased crude mortality up to 1 year after admission, none of the prolonged PT groups was independently associated with 30-day adjusted mortality. Comparison of the host response between patients with a normal PT or an extremely prolonged PT matched for baseline characteristics including severity of disease showed that an extremely prolonged PT was associated with impaired anticoagulant mechanisms, a more disturbed endothelial barrier integrity and increased systemic inflammation, and blood leukocyte transcriptomes indicating more prominent metabolic reprogramming and protein catabolism. Conclusion: A prolonged PT is associated with stronger anomalies in pathways implicated in the pathogenesis of sepsis, suggesting that activation of coagulation impacts other host response mechanisms.
AB - Background: A prolonged prothrombin time (PT) is a common feature in sepsis indicating consumptive coagulopathy. Objectives: To determine the association between a prolonged PT and aberrations in other host response mechanisms in sepsis. Methods: Patients admitted to the intensive care unit with sepsis were divided in quartiles according to the highest PT value measured within 24 h after admission. The host response was evaluated by measuring 19 plasma biomarkers reflecting pathways implicated in sepsis pathogenesis and by blood leukocyte gene expression profiling. Measurements and Main Results: Of 1524 admissions for sepsis, 386 (25.3%) involved patients with a normal PT (≤12.7 s); the remaining quartiles entailed 379 (24.9%) patients with a slightly prolonged PT (12.8 ≤ PT ≤ 15.0 s), 383 (25.1%) with an intermediately prolonged PT (15.1 ≤ PT ≤ 17.2 s), and 376 (24.7%) with an extremely prolonged PT (≥17.3 s). While patients with an extremely prolonged PT showed an increased crude mortality up to 1 year after admission, none of the prolonged PT groups was independently associated with 30-day adjusted mortality. Comparison of the host response between patients with a normal PT or an extremely prolonged PT matched for baseline characteristics including severity of disease showed that an extremely prolonged PT was associated with impaired anticoagulant mechanisms, a more disturbed endothelial barrier integrity and increased systemic inflammation, and blood leukocyte transcriptomes indicating more prominent metabolic reprogramming and protein catabolism. Conclusion: A prolonged PT is associated with stronger anomalies in pathways implicated in the pathogenesis of sepsis, suggesting that activation of coagulation impacts other host response mechanisms.
KW - endothelium inflammation
KW - host response
KW - intensive care unit
KW - prothrombin time
KW - sepsis
UR - http://www.scopus.com/inward/record.url?scp=85100970494&partnerID=8YFLogxK
U2 - 10.1111/jth.15246
DO - 10.1111/jth.15246
M3 - Article
C2 - 33492719
SN - 1538-7933
VL - 19
SP - 1049
EP - 1063
JO - Journal of Thrombosis and Haemostasis
JF - Journal of Thrombosis and Haemostasis
IS - 4
ER -