Postoperative fibrinolytic resistance is associated with early allograft dysfunction in liver transplantation: A prospective observational study.
Journal
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
ISSN: 1527-6473
Titre abrégé: Liver Transpl
Pays: United States
ID NLM: 100909185
Informations de publication
Date de publication:
01 07 2023
01 07 2023
Historique:
received:
01
09
2022
pmc-release:
01
07
2024
medline:
21
6
2023
pubmed:
8
2
2023
entrez:
7
2
2023
Statut:
ppublish
Résumé
Perioperative dysfunction of the fibrinolytic system may play a role in adverse outcomes for liver transplant recipients. There is a paucity of data describing the potential impact of the postoperative fibrinolytic system on these outcomes. Our objective was to determine whether fibrinolysis resistance (FR), on postoperative day one (POD-1), was associated with early allograft dysfunction (EAD). We hypothesized that FR, quantified by tissue plasminogen activator thrombelastography, is associated with EAD. Tissue plasminogen activator thrombelastography was performed on POD-1 for 184 liver transplant recipients at a single institution. A tissue plasminogen activator thrombelastography clot lysis at 30 minutes of 0.0% was identified as the cutoff for FR on POD-1. EAD occurred in 32% of the total population. Fifty-nine percent (n=108) of patients were categorized with FR. The rate of EAD was 42% versus 17%, p <0.001 in patients with FR compared with those without, respectively. The association between FR and EAD risk was assessed using multivariable logistic regression after controlling for known risk factors. The odds of having EAD were 2.43 times (95% CI, 1.07-5.50, p =0.03) higher in recipients with FR [model C statistic: 0.76 (95% CI, 0.64-0.83, p <0.001]. An additive effect of receiving a donation after circulatory determination of death graft and having FR in the rate of EAD was observed. Finally, compared with those without FR, recipients with FR had significantly shorter graft survival time ( p =0.03). In conclusion, FR on POD-1 is associated with EAD and decreased graft survival time. Postoperative viscoelastic testing may provide clinical utility in identifying patients at risk for developing EAD, especially for recipients receiving donation after circulatory determination of death grafts.
Identifiants
pubmed: 36749288
doi: 10.1097/LVT.0000000000000075
pii: 01445473-990000000-00082
pmc: PMC10293055
mid: NIHMS1870253
doi:
Substances chimiques
Tissue Plasminogen Activator
EC 3.4.21.68
Types de publication
Observational Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
724-734Subventions
Organisme : NHLBI NIH HHS
ID : R00 HL151887
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2023 American Association for the Study of Liver Diseases.
Références
Bezinover D, Dirkmann D, Findlay J, Guta C, Hartmann M, Nicolau-Raducu R, et al. Perioperative coagulation management in liver transplant recipients. Transplantation. 2018;102:578–92.
Moore HB, Yaffe H, Pomposelli JJ, Wachs M, Bak T, Kennealey P, 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;47:1912–4.
Nedel WL, Rodrigues Filho EM, Pasqualotto AC. Thrombin-activatable fibrinolysis inhibitor (TAFI) as a novel prognostic factor after orthotropic liver transplantation: a pilot study. Transplant Proc. 2015;47:1912–4.
Nicolau-Raducu R, Beduschi T, Vianna R, Diez C, Sleem M, Singh BP, et al. Fibrinolysis shutdown is associated with thrombotic and hemorrhagic complications and poorer outcomes after liver transplantation. Liver Transpl. 2019;25:380–7.
Hartmann M, Craciun B, Paul A, Brenner T, Saner FH. Pre-liver transplant ROTEM clot lysis index is associated with 30-day mortality, but is not a measure for fibrinolysis. J Clin Med. 2020;9:3298.
Kang YG, Martin DJ, Marquez J, Lewis JH, Bontempo FA, Shaw BW, et al. Intraoperative changes in blood coagulation and thrombelastographic monitoring in liver transplantation. Anesth Analg. 1985;64:888–96.
Hawkins RB, Raymond SL, Hartjes T, Efron PA, Larson SD, Andreoni KA, et al. Review: the perioperative use of thromboelastography for liver transplant patients. Transplant Proc. 2018;50:3552–8.
Bababekov YJ, Nydam TL, Pomposelli JJ, Moore HB. Goal-directed management of coagulation: the right treatment, the right patient, the right time. Transplantation. 2018;102:e303–4.
Meizoso JP, Karcutskie CA, Ray JJ, Namias N, Schulman CI, Proctor KG. Persistent fibrinolysis shutdown is associated with increased mortality in severely injured trauma patients. J Am Coll Surg. 2017;224:575–82.
Coleman JR, Moore EE, Sauaia A, Samuels JM, Moore HB, Ghasabyan A, et al. Untangling sex dimorphisms in coagulation: initial steps towards precision medicine for trauma resuscitation. Ann Surg. 2019;271:e128–ee130.
Moore HB, Moore EE, Gonzalez E, Huebner BJ, Sheppard F, Banerjee A, et al. Reperfusion shutdown: delayed onset of fibrinolysis resistance after resuscitation from hemorrhagic shock is associated with increased circulating levels of plasminogen activator inhibitor-1 and postinjury complications. Blood. 2016;128:206.
Feng S, Goodrich NP, Bragg-Gresham JL, Dykstra DM, Punch JD, DebRoy MA, et al. Characteristics associated with liver graft failure: the concept of a donor risk index. Am J Transplant. 2006;6:783–90.
Olthoff KM, Kulik L, Samstein B, Kaminski M, Abecassis M, Emond J, et al. Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors. Liver Transpl. 2010;16:943–49.
Moore HB, Moore EE, Chapman MP, Gonzalez E, Slaughter AL, Morton AP, et al. Viscoelastic measurements of platelet function, not fibrinogen function, predicts sensitivity to tissue-type plasminogen activator in trauma patients. J Thromb Haemost. 2015;13:1878–87.
Moore HB, Moore EE, Huebner BR, Dzieciatkowska M, Stettler GR, Nunns GR, et al. Fibrinolysis shutdown is associated with a fivefold increase in mortality in trauma patients lacking hypersensitivity to tissue plasminogen activator. J Trauma Acute Care Surg. 2017;83:1014–22.
Moore HB, Moore EE, Neal MD, Sheppard FR, Kornblith LZ, Draxler DF, et al. Fibrinolysis shutdown in trauma: historical review and clinical implications. Anesth Analg. 2019;129:762–773.
Schisterman EF, Perkins NJ, Liu A, Bondell H. Optimal cut-point and its corresponding Youden Index to discriminate individuals using pooled blood samples. Epidemiology. 2005;16:73–81.
Moore HB, Moore EE. Temporal changes in fibrinolysis following injury. Semin Thromb Hemost. 2020;46:189–98.
Moore HB. Fibrinolysis shutdown and hypofibrinolysis are not synonymous terms: the clinical significance of differentiating low fibrinolytic states. Semin Thromb Hemost. 2022; ahead of print:ahead of print. doi: 10.1055/s-0042-1758057
doi: 10.1055/s-0042-1758057
Nguyen G, Horellou M, Kruithof E, Conard J, Samama M. Residual plasminogen activator inhibitor activity after venous stasis as a criterion for hypofibrinolysis: a study in 83 patients with confirmed deep vein thrombosis. Blood. 1988;72:601–5.
Innes D, Sevitt S. Coagulation and fibrinolysis in injured patients. J Clin Pathol. 1964;17:1–13.
Moore HB, Moore EE, Gonzalez E, Chapman MP, Chin TL, Silliman CC, et al. Hyperfibrinolysis, physiologic fibrinolysis, and fibrinolysis shutdown: the spectrum of postinjury fibrinolysis and relevance to antifibrinolytic therapy. J Trauma Acute Care Surg. 2014;77:811–7; discussion 817.
Peduzzi P, Concato J, Feinstein AR, Holford TR. Importance of events per independent variable in proportional hazards regression analysis. II. Accuracy and precision of regression estimates. J Clin Epidemiol. 1995;48:1503–110.
Von Kaulla KN, Kaye H, von Kaulla E, Marchioro TL, Starzl TE. Changes in blood coagulation. Arch Surg. 1966;92:71–79.
Porte RJ, Bontempo FA, Knot EAR, Lewis JH, Kang YG, Starzl TE. Systemic effects of tissue plasminogen activator-associated fibrinolysis and its relation to thrombin generation in orthotopic liver transplantation. Transplantation. 1989;47:978–84.
Arshad F, Lisman T, Porte RJ. Hypercoagulability as a contributor to thrombotic complications in the liver transplant recipient. Liver Int. 2013;33:820–7.
Porte R. Coagulation and fibrinolysis in orthotopic liver transplantation: current views and insights. Semin Thromb Hemost. 1993;19:191–6.
Lisman T, Hernandez‐Gea V, Magnusson M, Roberts L, Stanworth S, Thachil J, 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;19:1116–22.
Leeper CM, Neal MD, McKenna CJ, Gaines BA. Trending fibrinolytic dysregulation: fibrinolysis shutdown in the days after injury is associated with poor outcome in severely injured children. Ann Surg. 2017;266:508–15.
Roberts DJ, Kalkwarf KJ, Moore HB, Ulbing S, Wiegele M, Lacom C, et al. Time course and outcomes associated with transient versus persistent fibrinolytic phenotypes after injury: a nested, prospective, multicenter cohort study. J Trauma Acute Care Surg. 2018;86:206–213.
Mutch NJ, Thomas L, Moore NR, Lisiak KM, Booth NA. TAFIa, PAI-1 and alpha-antiplasmin: complementary roles in regulating lysis of thrombi and plasma clots. J Thromb Haemost. 2007;5:812–7.
Llamas P, Cabrera R, Gómez-Arnau J, Fernández MN. Hemostasis and blood requirements in orthotopic liver transplantation with and without high-dose aprotinin. Haematologica. 1998;83:338–46.
Kuehn BM. First treatment for plasminogen deficiency is approved. JAMA. 2021;326:379.
Lozanovski VJ, Döhler B, Weiss KH, Mehrabi A, Süsal C. The differential influence of cold ischemia time on outcome after liver transplantation for different indications-who is at risk? A collaborative transplant study report. Front Immunol. 2020;11:892.
Hudcova J, Qasmi ST, Ruthazer R, Waqas A, Haider SB, Schumann R. Early allograft dysfunction following liver transplant: impact of obesity, diabetes, and red blood cell transfusion. Transplant Proc. 2021;53:119–23.
Vulliamy P, Gillespie S, Gall LS, Green L, Brohi K, Davenport RA. Platelet transfusions reduce fibrinolysis but do not restore platelet function during trauma hemorrhage. J Trauma Acute Care Surg. 2017;83:388–97.
Ostrowski SR, Berg RMG, Windeløv NA, Meyer MAS, Plovsing RR, Møller K, et al. Discrepant fibrinolytic response in plasma and whole blood during experimental endotoxemia in healthy volunteers. PloS One. 2013;8:e59368.
Tomescu D, Popescu M, Dima SO. Rotational thromboelastometry (ROTEM) 24 hours post liver transplantation predicts early allograft dysfunction. Rom J Anaesth Intensive Care. 2018;25:117–22.
Lee CF, Hung HC, Lee WC. Using rotational thromboelastometry to identify early allograft dysfunction after living donor liver transplantation. J Clin Med. 2021;10:3401.
Andert A, Becker N, Ulmer F, Schöning W, Hein M, Rimek A, et al. Liver transplantation and donor body mass index >30: use or refuse? Ann Transplant. 2016;21:185–93.
Bastos-Neves D, Salvalaggio PRO, Almeida MD. Risk factors, surgical complications and graft survival in liver transplant recipients with early allograft dysfunction. Hepatobiliary Pancreat Dis Int. 2019;18:423–9.
Mazilescu LI, Kotha S, Ghanekar A, Lilly L, Reichman TW, Galvin Z, et al. Early allograft dysfunction after liver transplantation with donation after circulatory death and brain death grafts: does the donor type matter? Transplant Direct. 2021;7:e727.
Croome KP, Marotta P, Wall WJ, Dale C, Levstik MA, Chandok N, et al. Should a lower quality organ go to the least sick patient? Model for end-stage liver disease score and donor risk index as predictors of early allograft dysfunction. Transplant Proc. 2012;44:1303–6.
Infanger L, Dibiasi C, Schaden E, Ulbing S, Wiegele M, Lacom C, et al. Comparison of the new viscoelastic coagulation analyzer ClotPro(R) with ROTEM(R) Delta and Conventional Coagulation Tests in critically ill patients with COVID-19. Front Med (Lausanne). 2021;8:777145.
Lisman T, Leebeek FWG, Meijer K, Van Der Meer J, Nieuwenhuis HK, De Groot PG. Recombinant factor VIIa improves clot formation but not fibrolytic potential in patients with cirrhosis and during liver transplantation. Hepatology. 2002;35:616–21.
Hardaway RM, Brune WH, Geever EF, Burns JW, Mock HP. Studies on the role of intravascular coagulation in irreversible hemorrhagic shock. Ann Surg. 1962;155:241–50.