[Platelet parameters and platelet Toll-like receptor 4 (TLR4) expression in patients with sepsis, and the effect of a joint treatment-plan integrating traditional Chinese and western medicine: a clinical study]

Abstract

Objective: To examine the efficacy of a treatment regimen combining modern (Western) medication and a traditional Chinese medicinal recipe Modified Liang-Ge San on sepsis, and its effect on platelet parameters/activation, platelet TLR4 expression and the intensity of inflammatory response in the patients.

Methods: 64 patients with sepsis were randomly assigned to two groups (32 each) to receive Western therapy only (group X) and Western therapy + Modified Liang-Ge San (group L). The values of: platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), the expression of TLR4 and procaspase activating compound-1 (PAC-1) in platelets, plasma concentration of soluble CD40 ligand (sCD40L) and tumor necrosis factor-α (TNF-α) were collected on the day of admission, and 3, 5, 9 days after treatment. Acute physiology and chronic health evaluation II (APACHE II) score, length of stay in intensive care unit (ICU), bleeding events and 28 day mortality in these patients were also analyzed. A group of 15 healthy volunteers (group C) were used as control.

Results: Compared to group C, the patients with sepsis have significantly: lower PLT (×10 9/L: 211.37±77.84 vs. 272.33±34.23, P< 0.01 ), increased MPV (fL: 10.24±0.81 vs. 9.64±0.66, P< 0.05) and PDW (fL: 17.79±1.68 vs. 15.61±1.54, P< 0.01), up-regulated platelet TLR4 [(39.93±9.07)% vs. (23.50±4.68)%] and PAC-1 expression [(42.21±8.74)% vs. (21.02±3.49)%], both P < 0.01, and higher level of sCD40L (μg/L: 6.94±1.05 vs. 3.27±0.41)and TNF-α(ng/L: 60.10±9.77 vs. 4.08±3.08), both P< 0.01. Compared to group X, group L had significantly (P< 0.05 or P< 0.01, respectively) lower value in: creatinine (μmol/L: 106.2±34.4 vs. 127.5±43.7); alanine aminotransferase (U/L: 31.7±12.5 vs. 41.9±19.9);aspartate aminotransferase (U/L: 54.1±21.6 vs. 68.5±24.1); TLR4 [(27.14±6.08)% vs. (30.92±5.47)%]; PAC-1 [(27.52±6.51)% vs. (31.24±5.77)%]; sCD40L (3.86±0.69 vs. 4.38±0.73); TNF-α (22.06±7.19 vs. 28.25±8.99), and higher PLT (261.93±55.32 vs. 231.37±63.58, P< 0.05), in the 9 days after treatment. In patients with sepsis, platelet PAC-1 expression correlated significantly to PLT ( r = - 0.409, P< 0.01 ) negatively, and MPV, PDW, platelet TLR4 expression, plasma sCD40L ( r (1) = 0.262, r (2) = 0.318, r (3) = 0.341, r(3) = 0.519, all P< 0.01) positively; sCD40L and TNF-α was positively correlated ( r = 0.542, P < 0.01 ) in these patients. In comparison with group X, the length of stay in ICU (day: 8.06±2.86 vs. 9.31±2.48), the incidence of bleeding (12.5% vs. 21.9%) and APACHE II score (12.75± 4.56 vs. 14.59± 3.97) were significantly lower (all P< 0.05) in group L on the 9 days after treatment. No significant difference was found in 28 day mortality between group L and X (15.63% vs. 18.75%, P> 0.05).

Conclusion: In patients with sepsis, platelet TLR4 expression is elevated together with platelet activation. The joint application of Western medicine and Modified Liang-Ge San may suppress such up-regulation in TLR4/other inflammatory mediators, and alleviate platelet activation/thrombocytopenia in these patients.