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      Comparison of Thromboelastography and Conventional Coagulation Tests in Patients With Severe Liver Disease

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          Abstract

          Objective:

          Thromboelastography (TEG) may provide rapid and clinically important coagulation information in acutely ill patients with chronic liver disease (CLD). Our objective was to describe the relationship between TEG and conventional coagulation tests (CCTs), which has not been previously explored in this population.

          Methods:

          In acutely ill patients with severe CLD (Child-Pugh score > 9, category C), we conducted a prospective observational study investigating coagulation assessment as measured by both CCTs and TEG. We used quantile regression to explore 30 associations between TEG parameters and corresponding CCTs. We compared TEG and CCT measures of coagulation initiation, clot formation, clot strength, and fibrinolysis.

          Results:

          We studied 34 patients on a total of 109 occasions. We observed inconsistent associations between TEG and CCT measures of coagulation initiation: TEG (citrated kaolin [CK] assay) standard reaction time and international normalized ratio: R 2 = 0.117 ( P = .044). Conversely, there were strong and consistent associations between tests of clot formation: TEG (CK) kinetics time and fibrinogen: R 2 = 0.202 ( P < .0001) and TEG (CK) α angle and fibrinogen 0.263 ( P < .0001). We also observed strong associations between tests of clot strength, specifically TEG MA and conventional fibrinogen levels, across all TEG assays: MA (CK) and fibrinogen: R 2 = 0.485 ( P < .0001). There were no associations between TEG and D-dimer levels.

          Conclusions:

          In acutely ill patients with CLD, there are strong and consistent associations between TEG measures of clot formation and clot strength and conventional fibrinogen levels. There are weak and/or inconsistent associations between TEG and all other conventional measures of coagulation.

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          Hyperfibrinolysis after major trauma: differential diagnosis of lysis patterns and prognostic value of thrombelastometry.

          Csilla Jambor, Michaela Pavelka, Herbert Schöchl … (2009)
          The aim of this study was to diagnose hyperfibrinolysis (HF) and its pattern using thrombelastometry and to correlate the diagnosis with mortality. Furthermore, routine laboratory based and the rotational thrombelastometry analyzer (ROTEM)-derived variables were also correlated with survival. Severe trauma patients showing HF in ROTEM were consecutively enrolled in the study. Three different HF patterns were compared: fulminant breakdown within 30 minutes, intermediate HF of 30 to 60 minutes, and late HF after 60 minutes. Injury severity score (ISS), hemodynamics, hemoglobin, hematocrit, platelet count (PC), fibrinogen, and ROTEM variables at admission were analyzed. The observed mortality was compared with the predicted trauma and injury severity score mortality. Thirty-three patients were diagnosed with HF. The mean ISS was 47 +/- 14. Fulminant, intermediate, or late HF (n = 11 each group) resulted in 100%, 91%, or 73% mortality, respectively, with the best prognosis for late HF (p = 0.0031). The actual overall mortality of HF (88%) exceeded the predicted trauma and injury severity score mortality (70%) (p = 0.039). Lower PC (123 +/- 53 vs. 193 +/- 91; p = 0.034), ROTEM prolonged clot formation time [CFT, 359 (140/632) vs. 82 (14/190); p = 0.042], and lower platelet contribution to maximum clot firmness [MCF(EXTEM) - MCF(FIBTEM), 34 (20/40) vs. 46 (40/53); p = 0.026] were associated with increased mortality. ROTEM-based diagnosis of HF predicted outcome. Further independent predictors of death were combination of HF with hemorrhagic shock, low PC, and prolonged CFT in ROTEM. ROTEM-based point of care testing in the emergency room is thus able to identify prognostic factors such as prolonged CFT and low platelet contribution to clot firmness (MCF(EX) - MCF(FIB)) earlier than standard laboratory-based monitoring.
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            Coagulation in liver disease: a guide for the clinician.

            Patrick Northup, Stephen H. Caldwell (2013)
            The human hemostasis system is complex and poorly understood after decades of intense scientific study. Despite multiple defects in routine coagulation laboratory studies in patients with chronic liver disease, there is growing evidence that these patients are effectively "rebalanced" with regard to procoagulant and anticoagulant activity and that most of these patients remain in a tenuous but balanced state of hemostasis. A major difficulty in the assessment of these patients is that there are no established laboratory tests that accurately reflect the changes in both the procoagulant and anticoagulant systems; therefore, routine laboratory testing is misleading to the clinician and may prompt inappropriate or risky therapies with little real benefit to the patient. The international normalized ratio is an example of this type of misleading test. Although the international normalized ratio is inextricably linked to prognosis and severity of protein synthetic dysfunction in acute and chronic liver disease, it is a very poor marker for bleeding risk and should not be used in isolation for this purpose. Coagulation disorders are critical in the management of frequent clinical scenarios such as esophageal variceal bleeding, invasive and percutaneous procedures, portal vein thrombosis, venous thromboembolism, and acute liver failure. This article summarizes the pathophysiology of hemostasis in liver disease, describes the strengths and weaknesses of various laboratory tests in assessment of these patients, and outlines the optimal management of hemostasis for some common clinical scenarios. Further research is needed for proper understanding of hemostasis in liver disease to optimally and safely manage these complex patients.
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              Thromboelastography as a better indicator of hypercoagulable state after injury than prothrombin time or activated partial thromboplastin time.

              Jeffrey A. Vos, Michael Dubick, John Holcomb … (2009)
              To investigate the hemostatic status of critically ill, nonbleeding trauma patients. We hypothesized that a hypercoagulable state exists in patients early after severe injury and that the pattern of clotting and fibrinolysis are similar between burned and nonburn trauma patients. Patients admitted to the surgical or burn intensive care unit within 24 hours after injury were enrolled. Blood samples were drawn on days 0 through 7. Laboratory tests included prothrombin time (PT), activated partial thromboplastin time (aPTT), levels of activated factor XI, D-dimer, protein C percent activity, antithrombin III percent activity, and thromboelastography (TEG). Study subjects were enrolled from April 1, 2004, to May 31, 2005, and included nonburn trauma patients (n = 33), burned patients (n = 25), and healthy (control) subjects (n = 20). Despite aggressive thromboprophylaxis, three subjects (2 burned and 1 nonburn trauma patients [6%]) had pulmonary embolism during hospitalization. Compared with controls, all patients had prolonged PT and aPTT (p < 0.05). The rate of clot formation (alpha angle) and maximal clot strength were higher for patients compared with those of controls (p < 0.05), indicating a hypercoagulable state. Injured patients also had lower protein C and antithrombin III percent activities and higher fibrinogen levels (p < 0.05 for all). Activated factor XI was elevated in 38% of patients (control subjects had undetectable levels). Thromboelastography analysis of whole blood showed that patients were in a hypercoagulable state; this was not detected by plasma PT or aPTT. The high incidence of pulmonary embolism indicated that our current prophylaxis regimen could be improved.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Clin Appl Thromb Hemost
                Journal ID (iso-abbrev): Clin. Appl. Thromb. Hemost
                Journal ID (publisher-id): CAT
                Journal ID (hwp): spcat
                Title: Clinical and Applied Thrombosis/Hemostasis
                Publisher: SAGE Publications (Sage CA: Los Angeles, CA )
                ISSN (Print): 1076-0296
                ISSN (Electronic): 1938-2723
                Publication date (Electronic): 4 June 2020
                Publication date Collection: Jan-Dec 2020
                Volume: 26
                Electronic Location Identifier: 1076029620925915
                Affiliations
                [1 ]Department of Intensive Care, Austin Health, Heidelberg, Melbourne, Australia
                [2 ]Department of Anaesthesia, Austin Health, Heidelberg, Melbourne, Australia
                [3 ]Department of Gastroenterology and Hepatology, Austin Health, Heidelberg, Melbourne, Australia
                [4 ]Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Karolinska Universitetssjukhuset, Solna, Sweden
                [5 ]Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
                [6 ]Department of Intensive Care, Melbourne Health, Parkville, Melbourne, Australia
                [7 ]Department of Epidemiology and Preventative Medicine, Monash University, Melbourne, Australia
                [8 ]Department of Intensive Care, The University of Melbourne, Austin Hospital, Melbourne, Australia
                Author notes
                [*]Rinaldo Bellomo, Department of Intensive Care, Austin Hospital, 145 Studley Rd, Heidelberg, Melbourne, Victoria 3084, Australia. Email: rinaldo.bellomo@ 123456austin.org.au
                Author information
                https://orcid.org/0000-0003-0260-6228
                https://orcid.org/0000-0001-8739-7896
                Article
                Publisher ID: 10.1177_1076029620925915
                DOI: 10.1177/1076029620925915
                PMC ID: 7427018
                PubMed ID: 32496878
                SO-VID: 10f7425e-bb44-4618-8992-cb18d5e6c9f9
                Copyright © © The Author(s) 2020
                License:

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                Date received : 23 February 2020
                Date revision received : 21 April 2020
                Date accepted : 21 April 2020
                Categories
                Subject: Original Article
                Custom metadata
                cover-date January-December 2020
                typesetter ts3

                Keywords: coagulopathy,coagulation,diagnosis,thrombosis
                Data availability:
                Keywords: coagulopathy, coagulation, diagnosis, thrombosis

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