Universität zu Köln

Vught, Lonneke A., Uhel, Fabrice, Ding, Chao, Van't Veer, Cees, Scicluna, Brendon P., Peters-Sengers, Hessel ORCID: 0000-0003-3145-864X, Klouwenberg, Peter M. C. Klein, Nuernberg, Peter, Cremer, Olaf L., Schultz, Marcus J. and van der Poll, Tom (2021). Consumptive coagulopathy is associated with a disturbed host response in patients with sepsis. J. Thromb. Haemost., 19 (4). S. 1049 - 1064. HOBOKEN: WILEY. ISSN 1538-7836

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Vught, Lonneke A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Uhel, Fabrice UNSPECIFIED UNSPECIFIED UNSPECIFIED Ding, Chao UNSPECIFIED UNSPECIFIED UNSPECIFIED Van't Veer, Cees UNSPECIFIED UNSPECIFIED UNSPECIFIED Scicluna, Brendon P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Peters-Sengers, Hessel UNSPECIFIED orcid.org/0000-0003-3145-864X UNSPECIFIED Klouwenberg, Peter M. C. Klein UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Cremer, Olaf L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schultz, Marcus J. UNSPECIFIED UNSPECIFIED UNSPECIFIED van der Poll, Tom UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-599145
DOI:	10.1111/jth.15246
Journal or Publication Title:	J. Thromb. Haemost.
Volume:	19
Number:	4
Page Range:	S. 1049 - 1064
Date:	2021
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1538-7836
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language Hematology; Peripheral Vascular Disease Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59914