Patients with
cirrhosis may display impaired or enhanced platelet activation, but the reasons for these equivocal findings are unclear. We investigated if bacterial
lipopolysaccharide (LPS) is implicated in platelet activation. In a cross-sectional study, conducted in an
ambulatory care clinic and hospital, comparing 69
cirrhosis patients and 30 controls matched for sex, age, and atherosclerotic risk factors, serum levels of LPS, soluble cluster of differentiation 40
ligand and
p-selectin (two markers of platelet activation), and
zonulin (a marker of gut permeability) were investigated. Ex vivo and in vitro studies were also performed to explore the effect of LPS on platelet activation. Compared to controls,
cirrhosis patients displayed higher serum levels of LPS (6.0 [4.0-17.5] versus 57.4 [43.4-87.2] pg/mL, P < 0.0001), soluble cluster of differentiation 40
ligand (7.0 ± 2.2 versus 24.4 ± 13.3 ng/mL, P < 0.0001), soluble
p-selectin (14.2 ± 4.05 versus 33.2 ± 15.2 ng/mL, P < 0.0001), and
zonulin (1.87 ± 0.84 versus 2.54 ± 0.94 ng/mL, P < 0.006). LPS significantly correlated with
zonulin (r = 0.45, P < 0.001). Ex vivo studies showed that platelets from
cirrhosis patients were more responsive to the agonists independently from platelet count; this phenomenon was blunted by incubation with an inhibitor of
Toll-like receptor 4. In vitro study by normal platelets showed that LPS alone (50-150 pg/mL) did not stimulate platelets but amplified platelet response to the
agonists; Toll-like receptor 4 inhibitor blunted this effect.
CONCLUSION: