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 × 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.