Principles, Interpretation, and Evidence-Based Role of Viscoelastic Point-of-Care Coagulation Assays in Cirrhosis and Liver Failure

Abstract

Background and aims: Standard coagulation tests such as prothrombin time, activated partial thromboplastin time, and international normalized ratio are determined by liver-synthesized coagulation factors. Despite an increased international normalized ratio, patients with cirrhosis are in a "rebalanced" state of hemostasis as the concomitant effect of reduced protein C, protein S, and thrombomodulin is not evaluated in standard coagulation tests. The cell-based model of hemostasis indicates additional mechanisms such as systemic inflammation, sepsis, and organ failures tip the delicate coagulation balance to an anticoagulant type in acute-on-chronic liver failure. In acute liver failure, thrombin generation and platelet function remain intact despite a marked prolongation in prothrombin time. We aimed to explain the principles, application, and utility of viscoelastic tests such as thromboelastography, rotational thromboelastometry, and Sonoclot.

Methods: We reviewed the available literature from MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trial with the search terms 'coagulation', 'cirrhosis', 'acute-on-chronic liver failure', 'thromboelastography', 'thromboelastometry' and 'sonoclot' for cross sectional studies, cohort studies and randomized trials.

Results: The point-of-care viscoelastic tests provide actionable targets for correcting the coagulation defect in a patient with bleeding and provide evidence-based algorithms for use in liver disease. A limitation of these tests is the inability to assess vessel injury and endothelial elements.

Conclusion: Global coagulation tests provide a comprehensive estimate of coagulation in vitro; however, their use has only been validated in the setting of liver transplantation. Newer guidelines for hemostatic resuscitation are now accepting these POC tests, but additional data are required to validate their use as standard of care.

Keywords: ACLF, acute-on-chronic liver failure; ACT, activated clotting time; ALF, acute liver failure; CR, clot rate; INR, international normalized ratio; MA, maximum amplitude; R, reaction time; ROTEM; ROTEM, rotational thromboelastometry; SCT, standard coagulation tests; TEG, thromboelastography; VWF, von Willebrand factor; aPTT, activated partial thromboplastin time; cirrhosis; coagulation; sonoclot; thromboelastography.

Figure 1

(A) Normal thromboelastography (TEG) trace showing coagulation variables. (B) Recognizable TEG traces which correspond to specific coagulation defects.

Figure 2

(A) Classical Sonoclot signature and stage of coagulation. (B) Abnormal Sonoclot signatures and coagulation scenarios such as hypercoagulable states, disseminated intravascular coagulation, and hyperfibrinolysis.

Figure 3

Classical rotational thromboelastometry graphical output and variations.

Figure 4

Transfusion algorithm based on standard coagulation tests.

Figure 5

Transfusion algorithm based on global coagulation tests.