title: Mediators of leukocyte activation play a role in disseminated intravascular coagulation during orthotopic liver transplantation.
abstract: Leukocytes play an important role in the development of disseminated intravascular coagulation (DIC). In the reperfusion phase of OLT a DIC-like situation has been described and has been held responsible for the high blood loss during this phase. We investigated the role of leukocytes in the pathogenesis of DIC in OLT by measuring the leukocytic mediators released upon activation (cathepsin B, elastase, TNF, neopterin) and the levels of thrombin-antithrombin III (TAT) complexes, seen as markers of prothrombin activation. Arterial blood samples were taken at 10 different time points during and after OLT. Samples were also taken of the perfusate released from the liver graft vein during the flushing procedure before the reperfusion phase. Aprotinin was given as a continuous infusion (0.2-0.4 Mill. KIU/hr) and its plasma levels were determined. Significantly elevated levels of neopterin (15-fold; P < 0.01), cathepsin B (440-fold; P < 0.01) in the perfusate, as compared with the systemic circulation, as well as their significant increases in the early reperfusion phase suggested that they were released by the graft liver. This was paralleled by elevated levels of elastase (1.3-fold, P < 0.05), TNF (1.5-fold, P = NS), and TAT complexes (1.4-fold; P < 0.1) in the perfusate. Significant correlations could be identified between the parameters of leukocyte activation and TAT complexes, whereas no correlation was observed between any of the parameters investigated and the aprotinin levels. Our results strongly indicate a release of leukocytic mediators from the graft liver during its reperfusion which seems to be related to the parallely increased prothrombin activation. No correlation could be seen between levels of aprotinin and levels of leukocytic mediators.
authors.affiliation: Department of Internal Medicine, University Hospital Rudolf Virchow, Berlin, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Himmelreich
authors.forename: M
authors.initials: M
authors.lastname: Jochum
authors.forename: W O
authors.initials: WO
authors.lastname: Bechstein
authors.forename: W
authors.initials: W
authors.lastname: Machleidt
authors.forename: P
authors.initials: P
authors.lastname: Neuhaus
authors.forename: K J
authors.initials: KJ
authors.lastname: Slama
authors.forename: H
authors.initials: H
authors.lastname: Riess
mesh_terms: D000328:Adult; D000368:Aged; D000990:Antithrombin III / Q000032:analysis; D007611:Aprotinin / Q000097:blood; D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D002401:Cathepsin B / Q000097:blood; D004211:Disseminated Intravascular Coagulation / Q000209:etiology*; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism / Q000502:physiology*; D016031:Liver Transplantation / Q000502:physiology*; D008213:Lymphocyte Activation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D019798:Neopterin; D010196:Pancreatic Elastase / Q000097:blood; D010447:Peptide Hydrolases / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D014409:Tumor Necrosis Factor-alpha; C046193:antithrombin III-protease complex; D001708:Biopterins; D019798:Neopterin; D000990:Antithrombin III; D007611:Aprotinin; D010447:Peptide Hydrolases; D010196:Pancreatic Elastase; D002401:Cathepsin B