Clinical Validation of Global Coagulation Tests to Guide Blood Component Transfusions in Cirrhosis and ACLF

Madhumita Premkumar, Rohit Mehtani, Smita Divyaveer, Kamal Kajal, Anand V Kulkarni, Syed Ahmed, Harmanpreet Kaur, Harpreet Kaur, Radhakrishna Dhiman, Ajay Duseja, Arka De, Madhumita Premkumar, Rohit Mehtani, Smita Divyaveer, Kamal Kajal, Anand V Kulkarni, Syed Ahmed, Harmanpreet Kaur, Harpreet Kaur, Radhakrishna Dhiman, Ajay Duseja, Arka De

Abstract

Background and aims: Patients with cirrhosis and acute-on-chronic liver failure (ACLF) may have bleeding complications and need for invasive procedures. Point-of-care (POC) coagulation tests like thromboelastography (TEG) and Sonoclot may be better for guiding patient management than the standard coagulation tests (SCTs), like prothrombin time, platelet count and international normalized ratio.

Methods: We prospectively compared and validated the POC tests and SCTs in 70 persons with ACLF and 72 persons with decompensated cirrhosis who had clinical bleeding and checked for episodes of re-bleeding and transfusion requirements. We assessed pre-procedure requirement of blood components when correction was done based on an SCT or POC strategy.

Results: Episodes of bleeding were seen in 45% and 28% of ACLF and cirrhosis patient, respectively (p=0.036), with the major site of bleeding being gastrointestinal (31% and 16%, respectively). Platelet counts correlated with TEG-maximum amplitude in cirrhosis (p=0.045) and prothrombin time correlated positively with TEG-reaction (R) time (p=0.032), TEG-Clot kinetics (K) time (p=0.042), Son-activated clotting time (p=0.038) and negatively with clot rate (p=0.043) in ACLF, making these correctable target variables in POC transfusion algorithms. Of 223 procedures, transfusion of fresh frozen plasma and platelet concentrate was reduced by 25% (p=0.035) and 20.8% (p=0.045) by using a POC strategy in 76 patients. Correction of deranged Son-activated clotting time and TEG-reaction time was noted in 68% and 72% after 24 h of fresh frozen plasma transfusion in ACLF and 85% and 80% in cirrhosis, respectively.

Conclusions: Our study clinically validates that POC tests can better detect coagulation defects and transfusion thresholds in ACLF and cirrhosis, whereas use of conventional tests appear to be less suitable in patients with clinical bleeding.

Trial registration: NCT04332484.

Keywords: ACLF; Cirrhosis; Coagulation; Sonoclot; Thromboelastography; Validation.

Conflict of interest statement

The authors have no conflict of interests related to this publication.

© 2021 Authors.

Figures

Fig. 1. Study participant enrollment flowchart.
Fig. 1. Study participant enrollment flowchart.
Fig. 2. Correlations of POC tests and…
Fig. 2. Correlations of POC tests and SCTs.
(A) TEG trace showing the stages of coagulation with corresponding standard coagulation tests. (B) Sonoclot signature showing the phases of clot formation and retraction, with corresponding standard coagulation tests.

References

    1. Fisher C, Patel VC, Stoy SH, Singanayagam A, Adelmeijer J, Wendon J, et al. Balanced haemostasis with both hypo- and hyper-coagulable features in critically ill patients with acute-on-chronic-liver failure. J Crit Care. 2018;43:54–60. doi: 10.1016/j.jcrc.2017.07.053.
    1. Bedreli S, Sowa JP, Gerken G, Saner FH, Canbay A. Management of acute-on-chronic liver failure: rotational thromboelastometry may reduce substitution of coagulation factors in liver cirrhosis. Gut. 2016;65:357–358. doi: 10.1136/gutjnl-2015-309922.
    1. Blasi A, Calvo A, Prado V, Reverter E, Reverter JC, Hernández-Tejero M, et al. Coagulation failure in patients with acute-on-chronic liver failure and decompensated cirrhosis: Beyond the international normalized ratio. Hepatology. 2018;68:2325–2337. doi: 10.1002/hep.30103.
    1. Premkumar M, Saxena P, Rangegowda D, Baweja S, Mirza R, Jain P, et al. 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. Liver Int. 2019;39:694–704. doi: 10.1111/liv.14034.
    1. Wang SC, Shieh JF, Chang KY, Chu YC, Liu CS, Loong CC, et al. Thromboelastography-guided transfusion decreases intraoperative blood transfusion during orthotopic liver transplantation: randomized clinical trial. Transplant Proc. 2010;42:2590–2593. doi: 10.1016/j.transproceed.2010.05.144.
    1. Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J, et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology. 2013;144:1426–1437. doi: 10.1053/j.gastro.2013.02.042. 1437.e1-9.
    1. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3) JAMA. 2016;315:801–810. doi: 10.1001/jama.2016.0287.
    1. Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005;3:692–694. doi: 10.1111/j.1538-7836.2005.01204.x.
    1. U.S. Food & Drug Administration. Analytical procedures and methods validation for drugs and biologics. Available from: . Accessed at July 2015.
    1. Solomon C, Asmis LM, Spahn DR. Is viscoelastic coagulation monitoring with ROTEM or TEG validated? Scand J Clin Lab Invest. 2016;76:503–507. doi: 10.1080/00365513.2016.1200136.
    1. Intagliata NM, Argo CK, Stine JG, Lisman T, Caldwell SH, Violi F. Concepts and controversies in haemostasis and thrombosis associated with liver disease: Proceedings of the 7th International Coagulation in Liver Disease Conference. Thromb Haemost. 2018;118:1491–1506. doi: 10.1055/s-0038-1666861.
    1. Royston D, von Kier S. Reduced haemostatic factor transfusion using heparinase-modified thrombelastography during cardiopulmonary bypass. Br J Anaesth. 2001;86:575–578. doi: 10.1093/bja/86.4.575.
    1. Spalding GJ, Hartrumpf M, Sierig T, Oesberg N, Kirschke CG, Albes JM. Cost reduction of perioperative coagulation management in cardiac surgery: value of “bedside” thrombelastography (ROTEM) Eur J Cardiothorac Surg. 2007;31:1052–1057. doi: 10.1016/j.ejcts.2007.02.022.
    1. Görlinger K, Pérez-Ferrer A, Dirkmann D, Saner F, Maegele M, Calatayud ÁAP, et al. The role of evidence-based algorithms for rotational thromboelastometry-guided bleeding management. Korean J Anesthesiol. 2019;72:297–322. doi: 10.4097/kja.19169.
    1. Kamath PS, Wiesner RH, Malinchoc M, Kremers W, Therneau TM, Kosberg CL, et al. A model to predict survival in patients with end-stage liver disease. Hepatology. 2001;33:464–470. doi: 10.1053/jhep.2001.22172.
    1. Barosa R, Roque Ramos L, Patita M, Nunes G, Fonseca J. CLIF-C ACLF score is a better mortality predictor than MELD, MELD-Na and CTP in patients with Acute on chronic liver failure admitted to the ward. Rev Esp Enferm Dig. 2017;109:399–405. doi: 10.17235/reed.2017.4701/2016.
    1. Drolz A, Horvatits T, Roedl K, Rutter K, Staufer K, Kneidinger N, et al. Coagulation parameters and major bleeding in critically ill patients with cirrhosis. Hepatology. 2016;64:556–568. doi: 10.1002/hep.28628.
    1. Coleman JR, Moore EE, Chapman MP, Banerjee A, Silliman CC, Ghasabyan A, et al. Rapid TEG efficiently guides hemostatic resuscitation in trauma patients. Surgery. 2018;164:489–493. doi: 10.1016/j.surg.2018.04.029.
    1. Hunt H, Stanworth S, Curry N, Woolley T, Cooper C, Ukoumunne O, et al. Thromboelastography (TEG) and rotational thromboelastometry (ROTEM) for trauma induced coagulopathy in adult trauma patients with bleeding. Cochrane Database Syst Rev. 2015;2015:CD010438. doi: 10.1002/14651858.CD010438.pub2.
    1. Peng HT, Nascimento B, Beckett A. Thromboelastography and thromboelastometry in assessment of fibrinogen deficiency and prediction for transfusion requirement: A descriptive review. Biomed Res Int. 2018;2018:7020539. doi: 10.1155/2018/7020539.
    1. Müller MCA, Meijers JC, van Meenen DM, Thachil J, Juffermans NP. Thromboelastometry in critically ill patients with disseminated intravascular coagulation. Blood Coagul Fibrinolysis. 2019;30:181–187. doi: 10.1097/MBC.0000000000000808.
    1. Whiting P, Al M, Westwood M, Ramos IC, Ryder S, Armstrong N, et al. Viscoelastic point-of-care testing to assist with the diagnosis, management and monitoring of haemostasis: a systematic review and cost-effectiveness analysis. Health Technol Assess. 2015;19:1–228. doi: 10.3310/hta19580.
    1. Terada R, Ikeda T, Mori Y, Yamazaki S, Kashiwabara K, Yamauchi H, et al. Comparison of two point of care whole blood coagulation analysis devices and conventional coagulation tests as a predicting tool of perioperative bleeding in adult cardiac surgery-a pilot prospective observational study in Japan. Transfusion. 2019;59:3525–3535. doi: 10.1111/trf.15523.
    1. Espinosa A, Stenseth R, Videm V, Pleym H. Comparison of three point-of-care testing devices to detect hemostatic changes in adult elective cardiac surgery: a prospective observational study. BMC Anesthesiol. 2014;14:80. doi: 10.1186/1471-2253-14-80.
    1. Rizzo K, Vella K, Zammit D, Gatt P, Grima C, Inguanez MB, et al. Fibrinogen measurement in liver disease: validation of the functional fibrinogen thromboelastography assay and a novel mathematical predictive model. Blood Transfus. 2019;17:237–246. doi: 10.2450/2018.0105-18.
    1. Görlinger K, Dirkmann D, Solomon C, Hanke AA. Fast interpretation of thromboelastometry in non-cardiac surgery: reliability in patients with hypo-, normo-, and hypercoagulability. Br J Anaesth. 2013;110:222–230. doi: 10.1093/bja/aes374.
    1. Petricevic M, Konosic S, Biocina B, Dirkmann D, White A, Mihaljevic MZ, et al. Bleeding risk assessment in patients undergoing elective cardiac surgery using ROTEM(®) platelet and Multiplate(®) impedance aggregometry. Anaesthesia. 2016;71:636–647. doi: 10.1111/anae.13303.
    1. Premkumar M, Bihari C, Saxena P, Devurgowda DR, Vyas T, Mirza R, et al. Heparin-like effect associated with risk of bleeding, sepsis, and death in patients with severe alcohol-associated hepatitis. Clin Gastroenterol Hepatol. 2020;18:486–495.e3. doi: 10.1016/j.cgh.2019.04.057.
    1. Premkumar M, Sarin SK. Current concepts in coagulation profile in cirrhosis and acute-on-chronic liver failure. Clin Liver Dis (Hoboken) 2020;16:158–167. doi: 10.1002/cld.976.

Source: PubMed

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