Coagulation failure is associated with bleeding events and clinical outcome during systemic inflammatory response and sepsis in acute‐on‐chronic liver failure: An observational cohort study

Abstract

Background Patients with acute‐on‐chronic liver failure (ACLF) have coagulation failure in the setting of systemic inflammatory syndrome (SIRS), sepsis and extra‐hepatic organ failures. Methods Consecutive ACLF patients without sepsis at baseline were assessed at days 0, 3 and 7 with thromboelastography (TEG) and specific assays (Factor VIII, von Willebrand factor [vWF], protein C and antithrombin III [ATIII]) and followed for development of sepsis, bleeding and outcome. Results Of 243 patients, 114 (63% ethanol related; mean age 44.3 ± 11.7 years; 90% male) were recruited. SIRS was noted in 39 (34.2%), 45 (39.5%) and 46 (40%) patients at days 0, 3 and 7 and sepsis in 28 (24%) and 52 (56.1%) patients at days 3 and 7 respectively. The 28‐ and 90‐day survivals were 62% and 51% respectively. A hypocoagulable TEG at baseline was a predictor of bleeding (hazard ratio [HR] 2.1; CI 1.6‐4.9; P = 0.050) and mortality (HR 1.9; CI 1.3‐7.9; P = 0.043). ACLF patients had increased Factor VIII, vWF, tissue factor levels and tissue plasminogen activator (tPA) activity with reduced protein C and ATIII. Coagulation parameters like Coagulation Index (HR 2.1; CI 1.1‐4.5; P = 0.044),clot lysis (HR 3.2; CI 1.9‐3.4; P = 0.033), low protein C < 30% (HR 2.1; CI 1.5‐2.8; P = 0.017), ATIII (HR 1.4; CI 1.7‐3.1; P = 0.052) and tPA (HR 1.5; CI 1.1‐2.4; P = 0.052) were predictors of mortality at day 28. Protein C activity <30% (HR 1.3; CI 1.0‐2.9; P = 0.042) and tPA >20 ng/mL (HR 1.2; CI 1.1‐2.1; P = 0.040) predicted mortality when adjusted for age, gender and baseline MELD. Conclusions Dynamic coagulation derangements, measured by TEG, determine the likelihood of bleeding and mortality in ACLF.

Relationship of thromboelastography and conventional clotting test values with severe bleeding in critically ill patients with coagulopathy: A prospective study

“…Overall, our results show that only pFB and TEG‐MA were moderately associated with severe bleeding, although their predictive ability was far from optimal. This is in line with the findings of previous publications, which produced heterogeneous results regarding the predictive value of SLTs and viscoelastic tests for bleeding in critically ill patients with coagulopathy. Differences in design, clinical scenarios, and the time of sampling could partially explain these controversial results.…”

“…In a post hoc analysis of 202 patients with sepsis, no association was observed between TEG parameters and subsequent bleeding; TEG variables at the baseline failed to identify septic patients with any bleeding episode in the ICU (AUC TEG‐R: 0.48 and TEG‐MA: 0.62). In a retrospective study including 243 patients with sepsis, a TEG‐R > 9 minutes or TEG‐MA < 18 mm were weak predictors of bleeding (HR 2.1 and 1.2, respectively, P < .01).…”

Mixed Fibrinolytic Phenotypes in Decompensated Cirrhosis and Acute‐on‐Chronic Liver Failure with Hypofibrinolysis in Those With Complications and Poor Survival

“…There is continuing interest in the use of anticoagulant agents, including heparin, antithrombin concentrate, tissue factor pathway inhibitor, activated protein C, and recombinant thrombomodulin in the treatment of sepsis, and all these agents are thought to be beneficial at least in part by reduction of intraorgan thrombosis. Although it is conceivable that such agents might benefit patients with ACLF as well, the use of anticoagulant agents is complicated by the extensive hemostatic changes in these patients . On the other hand, patients with sepsis without underlying liver disease may also have profound hemostatic changes, and it is incompletely defined what proportion of hemostatic changes in patients with ACLF is related to their underlying liver disease relative to the hemostatic changes induced by excessive inflammation and sepsis.…”

“…Patients with acute decompensation of cirrhosis (AD) or acute‐on‐chronic liver failure (ACLF) have progressive changes in their hemostatic system and are at particular risk for bleeding and thrombotic complications . Patients with ACLF are characterized by development of organ failure and high short‐term mortality .…”

Commentary on: Comparison of three transfusion protocols prior to central venous catheterization in patients with cirrhosis: A randomized controlled trial

“…This interaction will eventually upset the coagulation equilibrium and ultimately lead to bleeding or thrombosis. Recognition and treatment of external factors which precipitate acute hepatic decompensation may help mitigate risk . However, it is often challenging to estimate risk in patients with cirrhosis as currently available hemostatic measures do not accurately predict bleeding or thrombosis .…”