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 - This article is protected by copyright. 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85100970494&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/33492719
U2 - https://doi.org/10.1111/jth.15246
DO - https://doi.org/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 -