title: Liver grafts procured from donors after circulatory death have no increased risk of microthrombi formation.
abstract: Microthrombi formation provoked by warm ischemia and vascular stasis is thought to increase the risk of nonanastomotic strictures (NAS) in liver grafts obtained by donation after circulatory death (DCD). Therefore, potentially harmful intraoperative thrombolytic therapy has been suggested as a preventive strategy against NAS. Here, we investigated whether there is histological evidence of microthrombi formation during graft preservation or directly after reperfusion in DCD livers and the development of NAS. Liver biopsies collected at different time points during graft preservation and after reperfusion were triple-stained with hematoxylin-eosin (H & E), von Willebrand factor VIII (VWF), and Fibrin Lendrum (FL) to evaluate the presence of microthrombi. In a first series of 282 sections obtained from multiple liver segments of discarded DCD grafts, microthrombi were only present in 1%-3% of the VWF stainings, without evidence of thrombus formation in paired H & E and FL stainings. Additionally, analysis of 132 sections obtained from matched, transplanted donation after brain death and DCD grafts showed no difference in microthrombi formation (11.3% versus 3.3% respectively; P = 0.082), and no relation to the development of NAS (P = 0.73). Furthermore, no microthrombi were present in perioperative biopsies in recipients who developed early hepatic artery thrombosis. Finally, the presence of microthrombi did not differ before or after additional flushing of the graft with preservation solution. In conclusion, the results of our study derogate from the hypothesis that DCD livers have an increased tendency to form microthrombi. It weakens the explanation that microthrombi formation is a main causal factor in the development of NAS in DCD and that recipients could benefit from intraoperative thrombolytic therapy to prevent NAS following liver transplantation. Liver Transplantation 22 1676-1687 2016 AASLD.
authors.affiliation: Division of Hepatopancreatobiliary and Transplantation Surgery, Departments of Surgery, University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Cornelia J
authors.initials: CJ
authors.lastname: Verhoeven
authors.affiliation: Division of Hepatopancreatobiliary and Transplantation Surgery, Departments of Surgery, University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Tiarah C
authors.initials: TC
authors.lastname: Simon
authors.affiliation: Division of Hepatopancreatobiliary and Transplantation Surgery, Departments of Surgery, University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: de Jonge
authors.affiliation: Pathology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Michael
authors.initials: M
authors.lastname: Doukas
authors.affiliation: Pathology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Katharina
authors.initials: K
authors.lastname: Biermann
authors.affiliation: Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Herold J
authors.initials: HJ
authors.lastname: Metselaar
authors.affiliation: Division of Hepatopancreatobiliary and Transplantation Surgery, Departments of Surgery, University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Jan N M
authors.initials: JN
authors.lastname: Ijzermans
authors.affiliation: Division of Hepatopancreatobiliary and Transplantation Surgery, Departments of Surgery, University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Wojciech G
authors.initials: WG
authors.lastname: Polak
mesh_terms: D000368:Aged; D064591:Allografts / Q000098:blood supply* / Q000473:pathology; D001706:Biopsy; D001926:Brain Death; D003251:Constriction, Pathologic / Q000150:complications* / Q000209:etiology; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use; D006085:Graft Survival; D006323:Heart Arrest / Q000150:complications*; D006499:Hepatic Artery / Q000473:pathology; D006801:Humans; D007430:Intraoperative Care / Q000379:methods; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009926:Organ Preservation / Q000009:adverse effects; D012189:Retrospective Studies; D012307:Risk Factors; D015912:Thrombolytic Therapy / Q000009:adverse effects; D013927:Thrombosis / Q000517:prevention & control*; D014019:Tissue Donors; D009927:Tissue and Organ Procurement; D052096:Warm Ischemia / Q000009:adverse effects
chemical_list: D005343:Fibrinolytic Agents