Small Annexin V-Positive Platelet-Derived Microvesicles Affect Prognosis in Cirrhosis: A Longitudinal Study

Clin Transl Gastroenterol. 2021 Apr 28;12(5):e00333. doi: 10.14309/ctg.0000000000000333.


Introduction: Microvesicles (MVs) with procoagulant properties may favor liver parenchymal extinction, then cirrhosis-related complications and mortality. In a longitudinal cohort of cirrhotic patients, we measured plasma levels of platelet-derived MVs (PMVs), endothelial-derived MVs, and red blood cell-derived MVs, expressing phosphatidylserine (annexin V-positive [AV+]) or not, and evaluated their impact on Model for End-Stage Liver Disease (MELD) score and transplant-free survival.

Methods: MVs were quantified using flow cytometry in plasma from 90 noninfected cirrhotic patients and 10 healthy volunteers matched for age and sex. Impact of plasma microvesicle levels on 6-month transplant-free survival was assessed using log-rank tests and logistic regression.

Results: Microvesicle levels, mostly platelet-derived, were 2.5-fold higher in healthy volunteers compared with cirrhotic patients. Circulating small AV+ PMV levels were lower in cirrhotic patients (P = 0.014) and inversely correlated with MELD scores (R = -0.28; P = 0.0065). During 1-year follow-up, 8 patients died and 7 underwent liver transplantation. In the remaining patients, circulating microvesicle levels did not change significantly. Six-month transplant-free survival was lower in patients with low baseline small AV+ PMV levels (72.6% vs 96.2%; P = 0.0007). In multivariate analyses adjusted for age, ascites, esophageal varices, encephalopathy, clinical decompensation, total platelet counts, MELD score, and/or Child-Pugh C stage, patients with lower small AV+ PMV levels had a significant 5- to 8-fold higher risk of 6-month death or liver transplant. Other PMV levels did not impact on survival.

Discussion: Decreased circulating small AV+ PMV levels are associated with significantly lower transplant-free survival in cirrhotic patients independently of MELD score and platelet counts.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Annexin A5 / blood*
  • Blood Platelets / metabolism*
  • Case-Control Studies
  • Endothelium, Vascular / metabolism
  • Erythrocytes / metabolism
  • Female
  • Humans
  • Liver Cirrhosis / blood*
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / surgery
  • Liver Transplantation
  • Longitudinal Studies
  • Male
  • Microvessels / metabolism*
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Survival Analysis


  • ANXA5 protein, human
  • Annexin A5