title: Blood coagulation in anhepatic pigs: effects of treatment with the AMC-bioartificial liver.
abstract: The function of a newly devised bioartificial liver (AMC-BAL) based on viable, freshly isolated porcine hepatocytes has been evaluated in anhepatic pigs. The aim of this study was to assess the contribution of BAL treatment on blood coagulation parameters. Pigs were anesthetized and a total hepatectomy was performed (n = 15). The infrahepatic caval vein and the portal vein were connected to the subdiaphragmatic caval vein using a three-way prosthesis. Animals received standard intensive care (control, n= 5), treatment with an empty BAL (device control, n= 5) or with a cell-loaded BAL (BAL-treatment, n= 5) for a period of 24 h starting 24 h after hepatectomy. Coagulation parameters studied concerned prothrombin time (PT), platelet count, the procoagulant system (factors (F)II, FV, FVII, FVIII and fibrinogen), anticoagulant system (AT III), fibrinolytic system (t-PA, PAI-1) as well as markers of coagulation factor activation (TAT complexes, prothrombin fragment F1 + 2). FII, FV, FVII, AT III and fibrinogen rapidly decreased after total hepatectomy in pigs in accordance with the anhepatic state of the animals. FVIII levels were not influenced by the hepatectomy. A mild drop in platelet count was seen in all groups. Treatment of anhepatic pigs with the cell-loaded BAL did not restore PT or clotting factor levels. TAT and F1 + 2 complexes, however, were significantly increased in this group. Levels of t-PA and PAI-1 were not influenced by cell-loaded BAL treatment. Treatment of anhepatic pigs with the AMC-BAL based on freshly isolated porcine hepatocytes does not result in an improved coagulation state due to extensive consumption of clotting factors. However, increased levels of TAT complexes and prothrombin fragments F1 + 2 during treatment of anhepatic pigs indicate synthesis and direct activation of coagulation factors, leading to thrombin generation. This demonstrates that this bioartificial liver is capable of synthesizing coagulation factors.
authors.affiliation: Department of Surgery (Surgical Laboratory), Academic Medical Center, The University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: M N
authors.initials: MN
authors.lastname: Sosef
authors.forename: M-P
authors.initials: MP
authors.lastname: Van De Kerkhove
authors.forename: S L
authors.initials: SL
authors.lastname: Abrahamse
authors.forename: M M
authors.initials: MM
authors.lastname: Levi
authors.forename: R A F M
authors.initials: RA
authors.lastname: Chamuleau
authors.forename: T M
authors.initials: TM
authors.lastname: Van Gulik
mesh_terms: D000818:Animals; D000990:Antithrombin III; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation; D019774:Blood Coagulation Factor Inhibitors / Q000032:analysis; D001779:Blood Coagulation Factors / Q000032:analysis; D006498:Hepatectomy; D019164:Liver, Artificial / Q000592:standards*; D023421:Models, Animal; D010446:Peptide Fragments / Q000097:blood; D010447:Peptide Hydrolases / Q000097:blood; D019919:Prosthesis Implantation; D011516:Prothrombin; D011517:Prothrombin Time; D013552:Swine
chemical_list: D015415:Biomarkers; D019774:Blood Coagulation Factor Inhibitors; D001779:Blood Coagulation Factors; D010446:Peptide Fragments; C046193:antithrombin III-protease complex; C045879:prothrombin fragment 1.2; D000990:Antithrombin III; D011516:Prothrombin; D010447:Peptide Hydrolases