Haemostasis patterns in patients with acute-on-chronic liver failure and acute decompensation of cirrhosis including thromboelastometric tests with and without the addition of Protac: a pilot study

Abstract

Background Thromboelastometry is considered the best method to assesses hemostasis in liver disease. Diagnostic performance could be improved by adding protein C activators such as thrombomodulin or Protac®. We assessed changes in ROTEM parameters after the addition of Protac® in patients with acute-on-chronic liver failure (ACLF), acute decompensation (AD), and healthy individuals (HI) to define different hemostasis patterns, considering standard and velocity ROTEM parameters, and assess whether Protac® can improve the definition of the pattern. Methods Pre-test, we investigated whether diluted EXTEM reagent improved the effect of Protac® on the clotting time (CT)-ratio with and without Protac®. Ten ACLF and 20 AD patients and 21 HI were included in the main study. Results Standard EXTEM was used in the main study. INTEM CFT, INTEM A5 (inverse), and INTEM TPI (inverse) were the parameters that best differentiated liver disease from HI (ROC AUC, 0.921, 0.906, and 0.928, respectively; all P-values < 0.001). Combining INTEM CFT with EXTEM LI60-ratio only slightly improved the diagnostic performance (ROC AUC, 0.948; P < 0.001). EXTEM LI60 and INTEM maxV-t were the parameters that best differentiated between ACLF and AD patients (ROC AUC, 0.743, P = 0.033; and 0.723, P = 0.050; respectively). Combining EXTEM LI60 + INTEM maxV-t moderately improved the diagnostic performance (ROC AUC, 0.81, P < 0.001). Conclusions ROTEM velocity, fibrinolysis parameters and the indices calculated improve the diagnosis in combination with standard parameters (e.g., CFT and A5). Ratios calculated with and without Protac® (e.g., EXTEM LI60-ratio) only slightly increased the diagnostic performance in discriminating hemostasis patterns.

A combination of clot formation abnormalities in thromboelastometry has a high prognostic value in patients with acute-on-chronic liver failure

“…Individual ROTEM parameters showed higher rates of hypocoagulability in both ACLF and AD groups compared to healthy controls. However, most of them did not significantly differ between ACLF and AD groups, a finding which was also observed by previous researchers [12].…”

“…There is evidence that it may successfully reduce transfusions of blood components, administration of coagulation factors and anti-fibrinolytic drugs during liver transplantation or other interventions [13,14,31]. There are many ROTEM parameters that assess all the natural phases of clot attributes from initiation of clot formation to lysis [8,12,18]. However, in the current study, a more simplified method was used to determine different hemostatic phenotypes and interpret the clinical relevance of definite ‘hypocoagulable’ phenotype.…”

“…ROTEM was used as a reliable guide to hemostatic management of major surgical procedures in patients with liver cirrhosis, especially liver transplantation [9,10] or other invasive procedures [11]. However, limited data exist regarding the clinical relevance of ROTEM in acute-on-chronic liver failure (ACLF) [12][13][14][15][16], a syndrome characterized by extrahepatic multi-organ failures and high mortality [17], often requiring intensive care, red blood cells (RBCs) and blood products transfusions or probably coagulation factor concentrate administration [18,19]. Patients hospitalized for an acute episode of decompensation (AD group), which do not have multi-organ failures but increased systemic inflammatory reaction, have also been examined [20].…”