Thromboelastography and Utility in Hepatology Practice.

Review Thromboelastography and Utility in Hepatology Practice Abhishek Shenoy, M.D.,* and Nicolas M. Intagliata, M.D.*,† The coagulation system in liver disease is complex, and traditional coagulation tests, such as international normalized ratio (INR), do not predict bleeding risk.1-3 Thromboelastography (TEG) is a viscoelastic test (VET) that rapidly analyzes both the rate and strength of blood clot formation and the rate of dissolution in whole blood. Through use of whole blood, TEG more closely reflects in vivo hemostasis when compared with traditional coagulation plasma-based tests such as INR, activated partial thromboplastin time, and prothrombin time. Due to well-established shortcomings of traditional coagulation tests in cirrhosis, VETs are now increasingly studied and used in patients with cirrhosis. Given the broadly accepted shift in our understanding of hemostasis as “rebalanced” in liver disease, VETs (TEG and rotational thromboelastometry [ROTEM]) offer attractive features to both investigators and clinicians alike.4 Consequently, investigation and clinical use of VETs are expanding with aims of broader clinical applications.4-6 HOW IS IT PERFORMED? Conventional TEG is performed by adding a sample of blood into a cup that is then slowly rotated. A wire sensor is placed into the blood sample, and a clot is then formed between the sensor and the cup. A computer then analyzes the integrity and kinetics of clot formation, producing corresponding graphics and results in real time.7 ROTEM differs as the blood sample is placed in a stationary cup and a central rotating pin measures clot formation through an optical detection system, rather than a tracing wire affixed to a suspended pin in TEG.4 Separate TEG and ROTEM channels and assay types exist within VETs (Table 1), which allow simultaneous assessment of different components of hemostasis. Tracings and their associated changes are determined qualitatively and assist in determining a patient’s hemostasis and coagulopathy (Fig. 1). There are few studies that correlate TEG parameters well with traditional coagulation testing and subsequent bleeding or thrombotic events in patients with liver disease. The maximum amplitude (MA) in millimeters in TEG, shown in Fig. 1, is a measure of overall clot stiffness and an important tool that evaluates primary and secondary hemostasis, and helps guide platelet transfusion.4 An MA <50 to 55 mm signifies defective platelet contribution to coagulation and is a signal for platelet transfusion. Lower Abbreviations: ALF, acute liver failure; FFP, fresh frozen plasma; GPIIb/IIIa, glycoprotein IIb/IIIa; INR, international normalized ratio; MA, maximum amplitude (maximum diameter of clot); ROTEM, rotational thromboelastometry; TEG, thromboelastography; VET, viscoelastic test. From the * Department of Medicine, University of Virginia, Charlottesville, VA; and † Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, VA. Potential conflict of interest: N.M.I.’s institution received grants from Dova. Received December 1, 2019; accepted February 11, 2020. View this article online at wileyonlinelibrary.com © 2020 by the American Association for the Study of Liver Diseases | Clinical Liver Disease, VOL 16, NO 4, OCTOBER 2020 149   An Official Learning Resource of AASLD Review Thromboelastography and Utility in Hepatology Shenoy and Intagliata TABLE 1. VISCOELASTIC TEST PROPERTIES Interpretation TEG Channel Native TEG Rapid TEG Conventional/Standard TEG Heparinase TEG Functional fibrinogen TEG ROTEM Channel INTEM EXTEM FIBTEM APTEM HEPTEM Activator Sensitive channel for subtle changes in coagulopathy and hyperfibrinolysis Assays extrinsic pathway and common pathway Intrinsic/Extrinsic pathways activated with an “R” value corresponding to factor activity Determines whether patient is coagulopathic due to presence of heparin, combined with standard TEG Platelet inhibition and assesses fibrinogen contribution to clot strength None Tissue factor + kaolin Kaolin Heparinase GPIIb/IIIa inhibitor Intrinsic pathway activated Extrinsic pathway activated Isolates contribution of fibrinogen through platelet inhibition Fibrinolysis inhibition and may assist in confirming hyperfibrinolysis Heparin inhibition and assists in confirming presence of heparin Ellagic acid Tissue factor Cytochalasin D Aprotinin/Tranexamic acid Heparinase of how quickly the clot is broken down and if significantly elevated, it may be a sign of hyperfibrinolysis or rapid clot lysis that can be treated with antifibrinolytic agents. TEG PRIOR TO INVASIVE PROCEDURES IN CIRRHOSIS FIG. 1 (A) Fibrinolysis: normal R value with a continuous decreased MA. (B) Normal coagulation. (C) Hypercoagulable: decreased R and k values with increased alpha (α) angle and MA. α angle: rate of fibrin clot formation; k value: time to reach 20mm diameter; R value: time to clot formation. TEG may be a useful tool in measuring the severity of coagulopathy prior to invasive procedures in patients with cirrhosis. De Pietri et al.6 compared TEG-guided blood product use with standard traditional measures in a randomized prospective trial. TEG-guided transfusion resulted in significantly lower transfusions without an increase in bleeding complications.6 Given the conflicting literature on correcting platelet count and INR prior to invasive procedures, a TEG-guided transfusion protocol may offer advantages. Currently, however, it is unclear what standard baseline VET parameters should be used to guide prophylactic strategies because studies lack control arms without use of prophylaxis and have not been based on bleeding outcomes.8 TEG IN GASTROINTESTINAL BLEEDING MA values indicate lower platelet number and platelet dysfunction, as well as factor deficiency. Higher R times correlate with decreased clotting factors and indicate the need for factor replacement (e.g., fresh frozen plasma [FFP] transfusion or cryoprecipitate). Consistent with the majority of TEG studies, an R time cutoff of 8 to 10 minutes or longer signifies the need for factor replacement. An alpha angle less than 45 degrees may signify low or dysfunctional fibrinogen, necessitating fibrinogen replacement (e.g., fibrinogen or cryoprecipitate). Lysis time is a measure Patients with cirrhosis commonly experience gastrointestinal bleeding from portal hypertension and nonportal hypertension causative factors. In a randomized controlled trial, Kumar et al.9 evaluated a cohort of 96 patients with cirrhosis with nonvariceal bleeding. Patients were stratified into TEG-guided transfusion strategy or standard-of-care coagulation-based transfusion. The group in the TEG arm received significantly fewer blood product transfusions and had fewer adverse events related to transfusions. It should be noted that thresholds | Clinical Liver Disease, VOL 16, NO 4, OCTOBER 2020 150   An Official Learning Resource of AASLD Review Thromboelastography and Util (...truncated)