title: Platelet activation and increased tissue factor expression on monocytes in reperfusion injury following orthotopic liver transplantation.
abstract: Platelets have been implicated in the pathogenesis of liver damage after orthotopic liver transplantation (OLT). Early graft dysfunction is frequently caused by reperfusion injury subsequent to cold ischemia (IRI). Therefore, we investigated activation of the pivotal haemostatic cells, platelets and monocytes, from patients with elevated markers of IRI and from patients with uneventful course (control-group), respectively during the first week after OLT. Flow cytometry analysis of citrate anticoagulated blood samples revealed that platelets from IRI patients became significantly activated within 48 h after OLT in vivo, with increased surface presentation of P-selectin, CD40L, thrombospondin-1 and tissue-factor. Platelet activation in IRI patients on post-transplant day 2 was accompanied by significantly enhanced tissue-factor expression on peripheral blood monocytes, significant elevated levels of C-reactive protein and hepatocellular damage. Towards post-transplant day 4, levels of platelet-derived microparticles rose significantly in IRI patients if contrasted to control patients. Thus, activated cellular haemostasis is involved in the early inflammatory response of hepatocellular damage subsequent to reperfusion of the transplanted liver. Targeting distinct activation patterns of platelets and monocytes in an early phase of hepatic grafting may counteract the extent of IRI via inhibition of micro-thrombus formation and inflammation without exacerbating the existing bleeding risk.
authors.affiliation: General Surgery, Heinrich Heine University Duesseldorf, Duesseldorf, Germany. jan.schulteamesch@uni-duesseldorf.de
authors.forename: Jan Schulte Am
authors.initials: JS
authors.lastname: Esch
authors.forename: Kerstin
authors.initials: K
authors.lastname: Jurk
authors.forename: Wolfram T
authors.initials: WT
authors.lastname: Knoefel
authors.forename: Gesine
authors.initials: G
authors.lastname: Roeder
authors.forename: Holger
authors.initials: H
authors.lastname: Voss
authors.forename: Roy Y
authors.initials: RY
authors.lastname: Tustas
authors.forename: M
authors.initials: M
authors.lastname: Schmelzle
authors.forename: Andreas
authors.initials: A
authors.lastname: Krieg
authors.forename: Claus F
authors.initials: CF
authors.lastname: Eisenberger
authors.forename: Stefan
authors.initials: S
authors.lastname: Topp
authors.forename: Xavier
authors.initials: X
authors.lastname: Rogiers
authors.forename: Lutz
authors.initials: L
authors.lastname: Fischer
authors.forename: Hugo Van
authors.initials: HV
authors.lastname: Aken
authors.forename: Beate E
authors.initials: BE
authors.lastname: Kehrel
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000502:physiology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000473:pathology; D008099:Liver / Q000098:blood supply / Q000473:pathology; D008107:Liver Diseases / Q000097:blood* / Q000276:immunology / Q000473:pathology; D016031:Liver Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D015539:Platelet Activation / Q000502:physiology*; D011446:Prospective Studies; D015427:Reperfusion Injury / Q000097:blood* / Q000276:immunology; D013925:Thromboplastin / Q000096:biosynthesis*
chemical_list: D013925:Thromboplastin