• Claushuis Theodora A M TA Center for Experimental and Molecular Medicine, The Center for Infection and Immunity, and., Lonneke A van Vught, Brendon P Scicluna, Maryse A Wiewel, Peter M C Klein Klouwenberg, Arie J Hoogendijk, David S Y Ong, Olaf L Cremer, Janneke Horn, Marek Franitza, Mohammad R Toliat, Peter Nürnberg, Aeilko H Zwinderman, Marc J Bonten, Marcus J Schultz, Tom van der Poll, and Molecular Diagnosis and Risk Stratification of Sepsis Consortium.
• Center for Experimental and Molecular Medicine, The Center for Infection and Immunity, and.
• Blood. 2016 Jun 16; 127 (24): 3062-72.

AbstractPreclinical 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 × 10(9)/L, intermediate-low 50 × 10(9) to 99 × 10(9)/L, low 100 × 10(9) to 149 × 10(9)/L, or normal 150 × 10(9) to 399 × 10(9)/L) on admission to the intensive care unit. Sepsis patients with platelet counts <50 × 10(9)/L and 50 × 10(9) to 99 × 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 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 × 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 × 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.© 2016 by The American Society of Hematology.

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