Universität zu Köln

Claushuis, Theodora A. M., van Vught, Lonneke A., Scicluna, Brendon P., Wiewel, Maryse A., Klouwenberg, Peter M. C. Klein, Hoogendijk, Arie J., Ong, David S. Y., Cremer, Olaf L., Horn, Janneke, Franitza, Marek, Toliat, Mohammad R., Nuernberg, Peter, Zwinderman, Aeilko H., Bonten, Marc J., Schultz, Marcus J. and van der Poll, Tom (2016). Thrombocytopenia is associated with a dysregulated host response in critically ill sepsis patients. Blood, 127 (24). S. 3062 - 3073. WASHINGTON: AMER SOC HEMATOLOGY. ISSN 1528-0020

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Abstract

Preclinical studies have suggested that platelets influence the host response during sepsis. We sought to assess the association of admission thrombocytopenia with the presentation, outcome, and host response in patients with sepsis. Nine hundred thirty-one consecutive sepsis patients were stratified according to platelet counts very low <50 x 10(9)/L, intermediate-low 50 x 10(9) to 99 x 10(9)/L, low 100 x 10(9) to 149 x 10(9)/L, or normal 150 x 10(9) to 399 x 10(9)/L) on admission to the intensive care unit. Sepsis patients with platelet counts <50 x 10(9)/L and 50 x 10(9) to 99 x 10(9)/L presented with higher Acute Physiology and Chronic Health Evaluation scores and more shock. Both levels of thrombocytopenia were independently associated with increased 30-day mortality (hazard ratios with 95% confidence intervals 2.00 [1.32-3.05] and 1.72 [1.22-2.44], respectively). To account for baseline differences besides platelet 1.72 [1.22-2.44], respectively). To account for baseline differences besides platelet counts, propensity matching was performed, after which the association between thrombocytopenia and the host response was tested, as evaluated by measuring 17 plasma biomarkers indicative of activation and/or dysregulation of pathways implicated in sepsis pathogenesis and by whole genome blood leukocyte expression profiling. In the propensity matched cohort, platelet counts <50 x 10(9)/L were associated with increased cytokine levels and enhanced endothelial cell activation. All thrombocytopenic groups showed evidence of impaired vascular integrity, whereas coagulation activation was similar between groups. Blood microarray analysis revealed a distinct gene expression pattern in sepsis patients with <50 x 10(9)/L platelets, showing reduced signaling in leukocyte adhesion and diapedesis and increased complement signaling. These data show that admission thrombocytopenia is associated with enhanced mortality and a more disturbed host response during sepsis independent of disease severity, thereby providing clinical validity to animal studies on the role of platelets in severe infection.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Claushuis, Theodora A. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED van Vught, Lonneke A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Scicluna, Brendon P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiewel, Maryse A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Klouwenberg, Peter M. C. Klein UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoogendijk, Arie J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ong, David S. Y. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cremer, Olaf L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Horn, Janneke UNSPECIFIED UNSPECIFIED UNSPECIFIED Franitza, Marek UNSPECIFIED UNSPECIFIED UNSPECIFIED Toliat, Mohammad R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Zwinderman, Aeilko H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bonten, Marc J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schultz, Marcus J. UNSPECIFIED UNSPECIFIED UNSPECIFIED van der Poll, Tom UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-272166
DOI:	10.1182/blood-2015-11-680744
Journal or Publication Title:	Blood
Volume:	127
Number:	24
Page Range:	S. 3062 - 3073
Date:	2016
Publisher:	AMER SOC HEMATOLOGY
Place of Publication:	WASHINGTON
ISSN:	1528-0020
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INTENSIVE-CARE-UNIT; NEUTROPHIL EXTRACELLULAR TRAPS; MULTIPLE ORGAN DYSFUNCTION; SEPTIC SHOCK; CONSENSUS CONFERENCE; P-SELECTIN; ACTIVATED PLATELETS; ADHERENT PLATELETS; RISK-FACTORS; INFLAMMATION Multiple languages Hematology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27216