title: Activation of protein C during reperfusion in clinical liver transplantation.
abstract: BACKGROUND
  Activated protein C (APC) exhibits anticoagulant and antiinflammatory properties. We studied the kinetics and magnitude of protein C activation in clinical liver transplantation and the interaction of this activation with neutrophil and monocyte activation.
  
  
  METHODS
  In 10 patients undergoing liver transplantation, we measured plasma protein C and APC levels, neutrophil and monocyte CD11b and L-selectin expression, and leukocyte differential counts pre-, intra-, and postoperatively. Samples of blood entering and leaving the liver were obtained simultaneously to assess changes across the liver.
  
  
  RESULTS
  Protein C level was low preoperatively (65%, range 39%-141%) and remained low throughout surgery. Compared with the preoperative level (107%, range 78%-161%), APC level increased during liver reperfusion (471%, range 183%-917%, P=0.05). A transhepatic decrease in protein C level (-16%, range -45%-5%, P=0.007), but not in APC level, occurred during initial liver reperfusion. At the same time, neutrophil and monocyte activation took place in the liver.
  
  
  CONCLUSIONS
  Despite protein C deficiency, patients with liver insufficiency are able to maintain normal APC levels. During reperfusion, protein C consumption occurs in the liver without concomitant hepatic release of APC, indicating a shortage of APC in the reperfused liver. The process consuming protein C and APC may be related to the simultaneous ongoing neutrophil and monocyte activation within the liver graft, indicating a regulatory role for APC in inflammation.
authors.affiliation: Transplantation and Liver Surgery Clinic, Fourth Department of Surgery, University of Helsinki, Finland. minna.ilmakunnas@helsinki.fi
authors.forename: Minna
authors.initials: M
authors.lastname: Ilmakunnas
authors.forename: Jari
authors.initials: J
authors.lastname: Petäjä
authors.forename: Krister
authors.initials: K
authors.lastname: Höckerstedt
authors.forename: Heikki
authors.initials: H
authors.lastname: Mäkisalo
authors.forename: Jose A
authors.initials: JA
authors.lastname: Fernandez
authors.forename: John H
authors.initials: JH
authors.lastname: Griffin
authors.forename: Sten-Erik
authors.initials: SE
authors.lastname: Jansson
authors.forename: Heikki
authors.initials: H
authors.lastname: Repo
authors.forename: Eero J
authors.initials: EJ
authors.lastname: Pesonen
mesh_terms: D000328:Adult; D000368:Aged; D039481:CD11b Antigen / Q000378:metabolism; D005260:Female; D006499:Hepatic Artery; D006801:Humans; D019041:L-Selectin / Q000378:metabolism; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D010586:Phagocytes / Q000502:physiology; D011183:Postoperative Complications / Q000378:metabolism; D011486:Protein C / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism*; D013927:Thrombosis / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D011486:Protein C; D019041:L-Selectin