Normothermic Machine Perfusion Enhances Intraoperative Hepatocellular Synthetic Capacity: A Propensity Score-matched Analysis.

BACKGROUND Normothermic machine perfusion (NMP) of liver grafts is increasingly being incorporated in clinical practice. Current evidence has shown NMP plays a role in reconditioning the synthetic and energy capabilities of grafts. Intraoperative coagulation profile is a surrogate of graft quality and preservation status; however, to date this aspect has not been documented. METHODS The liver transplantation recipients who received NMP liver grafts in the QEHB between 2013 and 2016 were compared in terms of intraoperative thromboelastography characteristics (R time, K time, α-angle, maximum amplitude, G value, and LY30) to a propensity score-matched control group, where the grafts were preserved by traditional static cold storage (SCS). RESULTS After propensity matching, none of the thromboelastography characteristics were found to differ significantly between the 72 pairs of SCS and NMP organs when measured preimplantation. However, postimplantation, NMP organs had significantly shorter K time (median: 2.8 vs 3.6 min, P = 0.010) and R + K time (11.4 vs 13.7 min, P = 0.016), as well as significantly larger α-angle (55.9° vs 44.8°, P = 0.002), maximum amplitude (53.5 vs 49.6 mm, P = 0.044), and G values (5.8 vs 4.9k dynes/cm, P = 0.043) than SCS organs. Hyperfibrinolysis after implantation was also mitigated by NMP, with fewer patients requiring aggressive factor correction during surgery (LY30 = 0, NMP vs SCS: 83% vs 60%, P = 0.004). Consequently, NMP organs required significantly fewer platelet units to be transfused during the transplant procedure (median: 0 vs 5, P = 0.001). CONCLUSIONS In this study, we have shown that NMP liver grafts return better coagulation profiles intraoperatively, which could be attributed to the preservation of liver grafts under physiological conditions.

[1]  R. Porte,et al.  Production of Physiologically Relevant Quantities of Hemostatic Proteins During Ex Situ Normothermic Machine Perfusion of Human Livers , 2018, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[2]  N. Heaton,et al.  A randomized trial of normothermic preservation in liver transplantation , 2018, Nature.

[3]  Qiang Zhao,et al.  The first case of ischemia‐free organ transplantation in humans: A proof of concept , 2018, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[4]  W. Jassem,et al.  Normothermic Machine Preservation of the Liver: State of the Art , 2018, Current Transplantation Reports.

[5]  W. Baldwin,et al.  Lipid metabolism and functional assessment of discarded human livers with steatosis undergoing 24 hours of normothermic machine perfusion , 2018, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[6]  C. Watson,et al.  From “Gut Feeling” to Objectivity: Machine Preservation of the Liver as a Tool to Assess Organ Viability , 2018, Current Transplantation Reports.

[7]  E. Moore,et al.  Preoperative thrombelastography maximum amplitude predicts massive transfusion in liver transplantation. , 2017, The Journal of surgical research.

[8]  David D. Lee,et al.  Thromboelastography as a Predictor of Outcomes Following Liver Transplantation. , 2017, Transplantation proceedings.

[9]  P. Friend,et al.  Cold storage or normothermic perfusion for liver transplantation: probable application and indications , 2017, Current opinion in organ transplantation.

[10]  A. Gimson,et al.  Normothermic Perfusion in the Assessment and Preservation of Declined Livers Before Transplantation: Hyperoxia and Vasoplegia—Important Lessons From the First 12 Cases , 2017, Transplantation.

[11]  A. Gimson,et al.  Normothermic perfusion in the assessment and preservation of declined livers prior to transplantation: hyperoxia and vasoplegia - important lessons from the first 12 cases. , 2017, Transplantation.

[12]  J. Hodson,et al.  Preoperative Thromboelastography as a Sensitive Tool Predicting Those at Risk of Developing Early Hepatic Artery Thrombosis After Adult Liver Transplantation , 2016, Transplantation.

[13]  G. Rompianesi,et al.  Thromboelastographic reference ranges for a cirrhotic patient population undergoing liver transplantation , 2016, World journal of transplantation.

[14]  P. Friend,et al.  Normothermic Machine Perfusion of Deceased Donor Liver Grafts Is Associated With Improved Postreperfusion Hemodynamics , 2016, Transplantation direct.

[15]  N. Heaton,et al.  Liver Transplantation After Ex Vivo Normothermic Machine Preservation: A Phase 1 (First‐in‐Man) Clinical Trial , 2016, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[16]  F. Saner,et al.  Hemostasis in liver transplantation: Pathophysiology, monitoring, and treatment. , 2016, World journal of gastroenterology.

[17]  G. Reynolds,et al.  First human liver transplantation using a marginal allograft resuscitated by normothermic machine perfusion , 2016, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[18]  V. Serra,et al.  Reduced Transfusion During OLT by POC Coagulation Management and TEG Functional Fibrinogen: A Retrospective Observational Study , 2015, Transplantation direct.

[19]  David Calatayud Mizrahi,et al.  La máquina de perfusión normotérmica en el trasplante hepático con injertos provenientes de donación en asistolia , 2015 .

[20]  S. Mallett Clinical Utility of Viscoelastic Tests of Coagulation (TEG/ROTEM) in Patients with Liver Disease and during Liver Transplantation , 2015, Seminars in Thrombosis & Hemostasis.

[21]  Kenichi A. Tanaka,et al.  Clinical applicability of rapid thrombelastography and functional fibrinogen thrombelastography to adult liver transplantation , 2014, Liver transplantation.

[22]  G. Kazemier,et al.  Biomarkers to assess graft quality during conventional and machine preservation in liver transplantation. , 2014, Journal of hepatology.

[23]  S. Mallett,et al.  Transfusion and coagulation management in liver transplantation. , 2014, World journal of gastroenterology.

[24]  S. Mallett,et al.  Intraoperative hypercoagulability during liver transplantation as demonstrated by thromboelastography , 2013, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[25]  Johnny C. Hong,et al.  Ischaemia–reperfusion injury in liver transplantation—from bench to bedside , 2013, Nature Reviews Gastroenterology &Hepatology.

[26]  M. Tsou,et al.  Use of higher thromboelastogram transfusion values is not associated with greater blood loss in liver transplant surgery , 2012, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[27]  C. Fondevila,et al.  Extracorporeal machine liver perfusion: are we warming up? , 2012, Current opinion in organ transplantation.

[28]  William M. Lee,et al.  Minimal effects of acute liver injury/acute liver failure on hemostasis as assessed by thromboelastography. , 2012, Journal of hepatology.

[29]  M. Tsou,et al.  Thromboelastography-guided transfusion decreases intraoperative blood transfusion during orthotopic liver transplantation: randomized clinical trial. , 2010, Transplantation proceedings.

[30]  P. Friend,et al.  Advantages of normothermic perfusion over cold storage in liver preservation , 2002, Transplantation.

[31]  H. Jaeschke,et al.  Role of nitric oxide in the oxidant stress during ischemia/reperfusion injury of the liver. , 1992, Life sciences.

[32]  J H Lewis,et al.  Intraoperative Changes in Blood Coagulation and Thrombelastographic Monitoring in Liver Transplantation , 1985, Anesthesia and analgesia.