High plasma soluble thrombomodulin levels indicated poor prognosis of decompensated liver cirrhosis: a prospective cohort study

Abstract

Objective Hepatic sinusoidal endothelial injury is a prominent characteristic of liver cirrhosis. We determined plasma soluble thrombomodulin (sTM) levels in cirrhosis patients to evaluate the relationship between vascular injury and long-term prognosis. Methods A prospective single-center study was performed. The participants were followed up for every 6 months or until death or transplantation. A chemiluminescent enzyme immunoassay was used to establish a baseline sTM. Results Among the 219 patients with decompensated liver cirrhosis, 53.42% were caused by hepatitis B and hepatitis C. Plasma sTM levels were much higher in cirrhosis than in healthy controls and increased parallel with Child-Pugh classification (P < 0.01) and the amount of ascites (P = 0.04). After adjusting for sex, age, international normalized ratio, bilirubin, and other potential factors, multivariate Cox regression revealed that per TU/ml elevation of plasma sTM causes an increase of 8% in mortality, and per-SD elevation of thrombomodulin causes a 53% increase in mortality. As the mortality rates in low (5.90–12.60 TU/ml) and medium (12.70–18.00 TU/ml) sTM levels were similar, so we chose the cutoff of 18.00 TU/ml to divide into two groups, and K-M analysis indicated that patients with sTM >18.0 TU/ml demonstrated an additional 2.01 times death risk (95% CI, 1.13–7.93; P = 0.01) than those with sTM ≤18.0 TU/ml. Conclusion Plasma sTM in cirrhosis was significantly increased in parallel with the severity of liver dysfunction. sTM elevation than 18 TU/ml indicated a poor prognosis of decompensated liver cirrhosis.

Plasma thrombomodulin as a candidate biomarker for the diagnosis and prognosis of HBV-related acute-on-chronic liver failure

“…Some coagulation indicators were found to be correlated with plasma TM concentrations, such as PT, D dimer and INR, thus reflecting its important role in coagulation dysfunction. Since plasma TM is metabolized mainly by the liver and kidney, renal dysfunction can also result in an increase in plasma TM concentrations, 11 which may explain the positive correlation between Cr, serum urea, and plasma TM concentrations. Systemic inflammation is a major factor in determining the development, course, and prognosis of ACLF.…”

“…A prospective study found that high plasma soluble TM concentrations indicated poor prognosis of decompensated liver cirrhosis. 11 Analysis from a multicenter randomized controlled trial revealed that TM was associated with increased mortality rates and organ failure in children with acute respiratory failure who were ventilated mechanically. 25 One possible mechanism for the correlation between elevated plasma TM concentrations and poor clinical outcome is intravascular thrombosis, resulting in microcirculatory disturbance and multiorgan failure.…”

“…For example, Wei et al reported that high plasma TM concentrations could indicate poor prognosis in decompensated cirrhosis. 11 To the best of our knowledge, no previous research has been conducted to investigate the relationship between TM and HBV-ACLF. Therefore, this study aims to evaluate the diagnostic and prognostic value of TM measurements in HBV-ACLF patients.…”