Download PDF
CC BY-NC-ND 4.0 · Semin Thromb Hemost 2023; 49(02): 162-172
DOI: 10.1055/s-0042-1753530
Review Article

Thromboelastography-Guided Therapy Enhances Patient Blood Management in Cirrhotic Patients: A Meta-analysis Based on Randomized Controlled Trials

Jan Hartmann
1   Department of Medical Affairs, Clinical Development and Medical Safety, Haemonetics Corporation, Boston, Massachusetts
,
Joao D. Dias
1   Department of Medical Affairs, Clinical Development and Medical Safety, Haemonetics Corporation, Boston, Massachusetts
,
Evan G. Pivalizza
2   Department of Anesthesiology, UT Health McGovern Medical School, Houston, Texas
,
Guadalupe Garcia-Tsao
3   Yale University School of Medicine, Department of Internal Medicine, Section of Digestive Diseases, New Haven, Connecticut
4   VA CT Healthcare System, West Haven, Connecticut
› Author Affiliations Funding This work was funded by Haemonetics SA, Signy, Switzerland.
› Further Information
   Permissions and Reprints

Abstract

Patients with cirrhosis often have abnormal hemostasis, with increased risk of hemorrhage and thrombosis. Thromboelastography provides a rapid assessment of the coagulation status and can guide product transfusions in adult patients with cirrhosis. This study aimed to determine whether the use of thromboelastography in adult patients with cirrhosis decreases blood product use and impacts adverse events or mortality compared with standard practice. A registered (PROSPERO CRD42020192458) systematic review and meta-analysis was conducted for randomized controlled trials (RCTs) comparing thromboelastography-guided hemostatic management versus standard practice (control). Co-primary outcomes were the number of transfused platelet units and fresh frozen plasma (FFP) units. Secondary outcomes were mortality, adverse events, utilization of individual blood products, blood loss or excessive bleeding events, hospital/intensive care unit stay, and liver transplant/intervention outcomes. The search identified 260 articles, with five RCTs included in the meta-analysis. Platelet use was five times lower with thromboelastography versus the control, with a relative risk of 0.17 (95% confidence interval [CI]: [0.03–0.90]; p = 0.04), but FFP use did not differ significantly. Thromboelastography was associated with less blood product (p < 0.001), FFP + platelets (p < 0.001), and cryoprecipitate (p < 0.001) use. No differences were reported in bleeding rates or longer term mortality between groups, with the thromboelastography group having lower mortality at 7 days versus the control (relative risk [95% CI] = 0.52 [0.30–0.91]; p = 0.02). Thromboelastography-guided therapy in patients with cirrhosis enhances patient blood management by reducing use of blood products without increasing complications.

Keywords

thromboelastography - cirrhosis - blood products - patient blood management

Supplementary Material



Publication History

Article published online:
02 September 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 World Health organization. The urgent need to implement patient blood management: policy brief 2021. Accessed May 25, 2022 at: https://apps.who.int/iris/bitstream/handle/10665/346655/9789240035744-eng.pdf?sequence=1&isAllowed=y
    PubMedGoogle Scholar
  • 2 Tripodi A. Hemostasis abnormalities in cirrhosis. Curr Opin Hematol 2015; 22 (05) 406-412
    CrossrefPubMedGoogle Scholar
  • 3 Tripodi A, Primignani M, Chantarangkul V. et al. An imbalance of pro- vs anti-coagulation factors in plasma from patients with cirrhosis. Gastroenterology 2009; 137 (06) 2105-2111
    Google Scholar
  • 4 Blasi A, Cardenas A. Invasive procedures in patients with cirrhosis: a clinical approach based on current evidence. Clin Liver Dis 2021; 25 (02) 461-470
    CrossrefPubMedGoogle Scholar
  • 5 Lisman T, Hernandez-Gea V, Magnusson M. et al. The concept of rebalanced hemostasis in patients with liver disease: communication from the ISTH SSC working group on hemostatic management of patients with liver disease. J Thromb Haemost 2021; 19 (04) 1116-1122
    CrossrefPubMedGoogle Scholar
  • 6 Intagliata NM, Davis JPE, Caldwell SH. Coagulation pathways, hemostasis, and thrombosis in liver failure. Semin Respir Crit Care Med 2018; 39 (05) 598-608
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Saner FH, Kirchner C. Monitoring and treatment of coagulation disorders in end-stage liver disease. Visc Med 2016; 32 (04) 241-248
    CrossrefPubMedGoogle Scholar
  • 8 Tripodi A, Caldwell SH, Hoffman M, Trotter JF, Sanyal AJ. Review article: the prothrombin time test as a measure of bleeding risk and prognosis in liver disease. Aliment Pharmacol Ther 2007; 26 (02) 141-148
    CrossrefPubMedGoogle Scholar
  • 9 Dias JD, Sauaia A, Achneck HE, Hartmann J, Moore EE. Thromboelastography-guided therapy improves patient blood management and certain clinical outcomes in elective cardiac and liver surgery and emergency resuscitation: a systematic review and analysis. J Thromb Haemost 2019; 17 (06) 984-994
    CrossrefPubMedGoogle Scholar
  • 10 Hartmann J, Murphy M, Dias JD. Viscoelastic hemostatic assays: moving from the laboratory to the site of care-a review of established and emerging technologies. Diagnostics (Basel) 2020; 10 (02) 118
    CrossrefPubMedGoogle Scholar
  • 11 Malapati H, Hanwright PJ, Tuffaha SH. Utility of viscoelastic tests to predict flap thrombosis: a systematic review. Plast Reconstr Surg Glob Open 2021; 9 (08) e3769
    CrossrefPubMedGoogle Scholar
  • 12 De Pietri L, Bianchini M, Montalti R. et al. Thrombelastography-guided blood product use before invasive procedures in cirrhosis with severe coagulopathy: a randomized, controlled trial. Hepatology 2016; 63 (02) 566-573
    CrossrefPubMedGoogle Scholar
  • 13 Kang YG, Martin DJ, Marquez J. et al. Intraoperative changes in blood coagulation and thrombelastographic monitoring in liver transplantation. Anesth Analg 1985; 64 (09) 888-896
    PubMedGoogle Scholar
  • 14 Zanetto A, Rinder HM, Senzolo M, Simioni P, Garcia-Tsao G. Reduced clot stability by thromboelastography as a potential indicator of procedure-related bleeding in decompensated cirrhosis. Hepatol Commun 2020; 5 (02) 272-282
    CrossrefPubMedGoogle Scholar
  • 15 Odutayo A, Desborough MJ, Trivella M. et al. Restrictive versus liberal blood transfusion for gastrointestinal bleeding: a systematic review and meta-analysis of randomised controlled trials. Lancet Gastroenterol Hepatol 2017; 2 (05) 354-360
    CrossrefPubMedGoogle Scholar
  • 16 Mohanty A, Kapuria D, Canakis A. et al. Fresh frozen plasma transfusion in acute variceal haemorrhage: results from a multicentre cohort study. Liver Int 2021; 41 (08) 1901-1908
    CrossrefPubMedGoogle Scholar
  • 17 Zheng W, Zhao KM, Luo LH, Yu Y, Zhu SM. Perioperative single-donor platelet apheresis and red blood cell transfusion impact on 90-day and overall survival in living donor liver transplantation. Chin Med J (Engl) 2018; 131 (04) 426-434
    CrossrefPubMedGoogle Scholar
  • 18 Hartmann M, Walde C, Dirkmann D, Saner FH. Safety of coagulation factor concentrates guided by ROTEM™-analyses in liver transplantation: results from 372 procedures. BMC Anesthesiol 2019; 19 (01) 97
    CrossrefPubMedGoogle Scholar
  • 19 Spahn DR, Bouillon B, Cerny V. et al. The European guideline on management of major bleeding and coagulopathy following trauma: fifth edition. Crit Care 2019; 23 (01) 98
    CrossrefPubMedGoogle Scholar
  • 20 Kozek-Langenecker SA, Afshari A, Albaladejo P. et al. Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology. Eur J Anaesthesiol 2013; 30 (06) 270-382
    CrossrefPubMedGoogle Scholar
  • 21 Roullet S, de Maistre E, Ickx B. et al; GIHP. Position of the French Working Group on Perioperative Haemostasis (GIHP) on viscoelastic tests: what role for which indication in bleeding situations?. Anaesth Crit Care Pain Med 2019; 38 (05) 539-548
    CrossrefPubMedGoogle Scholar
  • 22 Boer C, Meesters MI, Milojevic M. et al; Task Force on Patient Blood Management for Adult Cardiac Surgery of the European Association for Cardio-Thoracic Surgery (EACTS) and the European Association of Cardiothoracic Anaesthesiology (EACTA). 2017 EACTS/EACTA guidelines on patient blood management for adult cardiac surgery. J Cardiothorac Vasc Anesth 2018; 32 (01) 88-120
    CrossrefPubMedGoogle Scholar
  • 23 Pagano D, Milojevic M, Meesters MI. et al. 2017 EACTS/EACTA guidelines on patient blood management for adult cardiac surgery. Eur J Cardiothorac Surg 2018; 53 (01) 79-111
    CrossrefPubMedGoogle Scholar
  • 24 Bugaev N, Como JJ, Golani G. et al. Thromboelastography and rotational thromboelastometry in bleeding patients with coagulopathy: Practice management guideline from the Eastern Association for the Surgery of Trauma. J Trauma Acute Care Surg 2020; 89 (06) 999-1017
    CrossrefPubMedGoogle Scholar
  • 25 National Blood Authority Australia. Patient blood management guidelines: module 1 critical bleeding massive transfusion. 2013. Accessed May 25, 2022 at: https://www.blood.gov.au/system/files/documents/Module%201.pdf
    PubMedGoogle Scholar
  • 26 O'Leary JG, Greenberg CS, Patton HM, Caldwell SH. AGA clinical practice update: coagulation in cirrhosis. Gastroenterology 2019; 157 (01) 34-43.e1
    CrossrefPubMedGoogle Scholar
  • 27 Nanchal R, Subramanian R, Karvellas CJ. et al. Guidelines for the management of adult acute and acute-on-chronic liver failure in the ICU: cardiovascular, endocrine, hematologic, pulmonary, and renal considerations. Crit Care Med 2020; 48 (03) e173-e191
    CrossrefPubMedGoogle Scholar
  • 28 Roberts LN, Lisman T, Stanworth S. et al. Periprocedural management of abnormal coagulation parameters and thrombocytopenia in patients with cirrhosis: guidance from the SSC of the ISTH. J Thromb Haemost 2022; 20 (01) 39-47
    CrossrefPubMedGoogle Scholar
  • 29 Gurusamy KS, Pissanou T, Pikhart H, Vaughan J, Burroughs AK, Davidson BR. Methods to decrease blood loss and transfusion requirements for liver transplantation. Cochrane Database Syst Rev 2011; (12) CD009052
    PubMedGoogle Scholar
  • 30 Moher D, Liberati A, Tetzlaff J, Altman DG. PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg 2010; 8 (05) 336-341
    CrossrefPubMedGoogle Scholar
  • 31 Sterne JAC, Savović J, Page MJ. et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 2019; 366: l4898
    Google Scholar
  • 32 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7 (03) 177-188
    Google Scholar
  • 33 Kumar M, Ahmad J, Maiwall R. et al. Thromboelastography-guided blood component use in patients with cirrhosis with nonvariceal bleeding: a randomized controlled trial. Hepatology 2020; 71 (01) 235-246
    CrossrefPubMedGoogle Scholar
  • 34 Rout G, , Shalimar, Gunjan D. et al. Thromboelastography-guided blood product transfusion in cirrhosis patients with variceal bleeding: a randomized controlled trial. J Clin Gastroenterol 2020; 54 (03) 255-262
    CrossrefPubMedGoogle Scholar
  • 35 Vuyyuru SK, Singh AD, Gamanagatti SR, Rout G, Gunjan D. , Shalimar. A randomized control trial of thromboelastography-guided transfusion in cirrhosis for high-risk invasive liver-related procedures. Dig Dis Sci 2020; 65 (07) 2104-2111
    CrossrefPubMedGoogle Scholar
  • 36 Wang SC, Shieh JF, Chang KY. et al. Thromboelastography-guided transfusion decreases intraoperative blood transfusion during orthotopic liver transplantation: randomized clinical trial. Transplant Proc 2010; 42 (07) 2590-2593
    CrossrefPubMedGoogle Scholar
  • 37 Benson AB, Austin GL, Berg M. et al. Transfusion-related acute lung injury in ICU patients admitted with gastrointestinal bleeding. Intensive Care Med 2010; 36 (10) 1710-1717
    CrossrefPubMedGoogle Scholar
  • 38 Vipani A, Lindenmeyer CC, Sundaram V. Treatment of severe acute on chronic liver failure: management of organ failures, investigational therapeutics, and the role of liver transplantation. J Clin Gastroenterol 2021; 55 (08) 667-676
    CrossrefPubMedGoogle Scholar
  • 39 Tangcheewinsirikul N, Moonla C, Uaprasert N, Pittayanon R, Rojnuckarin P. Viscoelastometric versus standard coagulation tests to guide periprocedural transfusion in adults with cirrhosis: a meta-analysis of randomized controlled trials. Vox Sang 2022; 117 (04) 553-561
    CrossrefPubMedGoogle Scholar
  • 40 Kovalic AJ, Khan MA, Malaver D. et al. Thromboelastography versus standard coagulation testing in the assessment and reversal of coagulopathy among cirrhotics: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2020; 32 (03) 291-302
    CrossrefPubMedGoogle Scholar
  • 41 Bonnet A, Gilquin N, Steer N. et al. The use of a thromboelastometry-based algorithm reduces the need for blood product transfusion during orthotopic liver transplantation: a randomised controlled study. Eur J Anaesthesiol 2019; 36 (11) 825-833
    CrossrefPubMedGoogle Scholar
  • 42 Rocha LL, Neto AS, Pessoa CMS. et al. Comparison of three transfusion protocols prior to central venous catheterization in patients with cirrhosis: a randomized controlled trial. J Thromb Haemost 2020; 18 (03) 560-570
    CrossrefPubMedGoogle Scholar
  • 43 Shenoy A, Louissaint J, Shannon C, Tapper EB, Lok AS. Viscoelastic testing prior to non-surgical procedures reduces blood product use without increasing bleeding risk in cirrhosis. Dig Dis Sci 2022; 7 (11) 5290-5299
    CrossrefPubMedGoogle Scholar
  • 44 Ziegler B, Voelckel W, Zipperle J, Grottke O, Schöchl H. Comparison between the new fully automated viscoelastic coagulation analysers TEG 6s and ROTEM Sigma in trauma patients: a prospective observational study. Eur J Anaesthesiol 2019; 36 (11) 834-842
    CrossrefPubMedGoogle Scholar
  • 45 Idowu O, Ifeanyi-Pillette I, Owusu-Agyemang P. et al. The quantra hemostasis analyzer compared to thromboelastography (TEG) in the surgical oncologic population: a prospective observational trial. J Surg Oncol 2021; 124 (05) 894-905
    CrossrefPubMedGoogle Scholar
  • 46 Neal MD, Moore EE, Walsh M. et al. A comparison between the TEG 6s and TEG 5000 analyzers to assess coagulation in trauma patients. J Trauma Acute Care Surg 2020; 88 (02) 279-285
    CrossrefPubMedGoogle Scholar
  • 47 Lloyd-Donald P, Vasudevan A, Angus P. et al. Comparison of thromboelastography and conventional coagulation tests in patients with severe liver disease. Clin Appl Thromb Hemost 2020; 26: 1076029620925915
    CrossrefPubMedGoogle Scholar
  • 48 Oo J, Allen M, Loveday BPT. et al. Coagulation in liver surgery: an observational haemostatic profile and thromboelastography study. ANZ J Surg 2020; 90 (06) 1112-1118
    CrossrefPubMedGoogle Scholar
  • 49 Brown CV, Foulkrod KH, Sadler HT. et al. Autologous blood transfusion during emergency trauma operations. Arch Surg 2010; 145 (07) 690-694
    CrossrefPubMedGoogle Scholar
  • 50 Marcucci C, Madjdpour C, Spahn DR. Allogeneic blood transfusions: benefit, risks and clinical indications in countries with a low or high human development index. Br Med Bull 2004; 70: 15-28
    CrossrefPubMedGoogle Scholar
  • 51 Debernardi Venon W, Ponzo P, Sacco M. et al. Usefulness of thromboelastometry in predicting the risk of bleeding in cirrhotics who undergo invasive procedures. Eur J Gastroenterol Hepatol 2015; 27 (11) 1313-1319
    CrossrefPubMedGoogle Scholar
  • 52 Keding V, Zacharowski K, Bechstein WO, Meybohm P, Schnitzbauer AA. Patient Blood Management improves outcome in oncologic surgery. World J Surg Oncol 2018; 16 (01) 159
    CrossrefPubMedGoogle Scholar
  • 53 Gani F, Cerullo M, Ejaz A. et al. Implementation of a blood management program at a tertiary care hospital: effect on transfusion practices and clinical outcomes among patients undergoing surgery. Ann Surg 2019; 269 (06) 1073-1079
    CrossrefPubMedGoogle Scholar
  • 54 Gupta PB, DeMario VM, Amin RM. et al. Patient blood management program improves blood use and clinical outcomes in orthopedic surgery. Anesthesiology 2018; 129 (06) 1082-1091
    CrossrefPubMedGoogle Scholar
  • 55 Weber CF, Görlinger K, Meininger D. et al. Point-of-care testing: a prospective, randomized clinical trial of efficacy in coagulopathic cardiac surgery patients. Anesthesiology 2012; 117 (03) 531-547
    CrossrefPubMedGoogle Scholar
  • 56 So-Osman C, Nelissen RG, Koopman-van Gemert AW. et al. Patient blood management in elective total hip- and knee-replacement surgery (Part 1): a randomized controlled trial on erythropoietin and blood salvage as transfusion alternatives using a restrictive transfusion policy in erythropoietin-eligible patients. Anesthesiology 2014; 120 (04) 839-851
    CrossrefPubMedGoogle Scholar
  • 57 Pustavoitau A, Rizkalla NA, Perlstein B. et al. Validation of predictive models identifying patients at risk for massive transfusion during liver transplantation and their potential impact on blood bank resource utilization. Transfusion 2020; 60 (11) 2565-2580
    CrossrefPubMedGoogle Scholar
  • 58 Schulick AC, Moore HB, Walker CB. et al. A clinical coagulopathy score concurrent with viscoelastic testing defines opportunities to improve hemostatic resuscitation and enhance blood product utilization during liver transplantation. Am J Surg 2020; 220 (06) 1379-1386
    CrossrefPubMedGoogle Scholar
  • 59 Moore HB, Yaffe H, Pomposelli JJ. et al. Detection of early allograft dysfunction at 30 min of reperfusion in liver transplantation: an intraoperative diagnostic tool with real time assessment of graft function. Am J Surg 2020; 220 (06) 1518-1525
    CrossrefPubMedGoogle Scholar
  • 60 Mpaili E, Tsilimigras DI, Moris D. et al. Utility of viscoelastic coagulation testing in liver surgery: a systematic review. HPB (Oxford) 2021; 23 (03) 331-343
    CrossrefPubMedGoogle Scholar
  • 61 Janko N, Majeed A, Kemp W, Roberts SK. Viscoelastic tests as point-of-care tests in the assessment and management of bleeding and thrombosis in liver disease. Semin Thromb Hemost 2020; 46 (06) 704-715
    Article in Thieme ConnectPubMedGoogle Scholar
  • 62 Rovegno M, Vera M, Ruiz A, Benítez C. Current concepts in acute liver failure. Ann Hepatol 2019; 18 (04) 543-552
    CrossrefPubMedGoogle Scholar
  • 63 Premkumar M, Mehtani R, Divyaveer S. et al. Clinical validation of global coagulation tests to guide blood component transfusions in cirrhosis and ACLF. J Clin Transl Hepatol 2021; 9 (02) 210-219
    PubMedGoogle Scholar
  • 64 Saluja V, Tiwari S, Mitra LG, Kumar G, Maiwall R, Rajan V. Tracheostomy in critically ill liver disease patients with coagulopathy: a retrospective study at a tertiary center. Int J Crit Illn Inj Sci 2020; 10 (04) 195-199
    CrossrefPubMedGoogle Scholar