title: C1-inhibitor efficiently delays clot development in normal human whole blood and inhibits Escherichia coli-induced coagulation measured by thromboelastometry.
abstract: BACKGROUND
  C1-inhibitor (C1-INH), a serine protease inhibitor in plasma plays a central role in the cross-talk among the complement, coagulation, fibrinolytic and kallikrein-kinin systems. However, previous reports indicate thrombotic risks in children following supraphysiological dosing with C1-INH.
  
  
  OBJECTIVE
  To investigate the role of supraphysiological C1-INH concentrations in clot development with and without addition of Escherichia coli (E. coli) in fresh human whole blood using thromboelastometry.
  
  
  METHODS
  Blood was collected in citrate tubes, and C1-INH (3.0 to 47.6μM) or human serum albumin (HSA) was added as a control. Activated partial thromboplastin time (aPTT) was analysed in the plasma. The analyses non-activated thromboelastometry (NATEM), extrinsic (EXTEM) or intrinsic thromboelastometry (INTEM) were performed using rotational thromboelastometry.
  
  
  RESULTS
  C1-INH increased aPTT 1.8-fold (p< 0.05), whereas HSA had no effect. C1-INH increased NATEM clotting time (CT) from 789s to 2025 s (p< 0.05) in a dose-dependent manner. C1-INH reduced the NATEM alpha angle from 47 to 28° (p<0.05) and increased the NATEM clot formation time from 261s to 595s (p< 0.05). E. coli significantly reduced the NATEM CT after 120min of incubation. C1-INH prevented E. coli-induced activation (p< 0.05). C1-INH significantly increased the INTEM CT (p< 0.05), but had no effect on EXTEM CT. C1-INH (47.6μM) significantly reduced fibrinolysis measured as NATEM and EXTEM lysis indices LI60.
  
  
  CONCLUSIONS
  Supraphysiological C1-INH concentrations have dose-dependent anticoagulant effects in human whole blood in vitro. At very high levels C1-INH also inhibits fibrinolysis.
authors.affiliation: Research Laboratory, Nordland Hospital, Bodø, Norway; Institute of Clinical Medicine, University of Tromsø - The Arctic University of Norway, Tromsø, Norway. Electronic address: anne.landsem@nlsh.no.
authors.forename: A
authors.initials: A
authors.lastname: Landsem
authors.affiliation: Research Laboratory, Nordland Hospital, Bodø, Norway.
authors.forename: H
authors.initials: H
authors.lastname: Fure
authors.affiliation: Research Laboratory, Nordland Hospital, Bodø, Norway; Institute of Clinical Medicine, University of Tromsø - The Arctic University of Norway, Tromsø, Norway; Faculty of Health Sciences, K.G. Jebsen TREC, University of Tromsø - The Arctic University of Norway, Tromsø, Norway; Department of Immunology, Oslo University Hospital, and K.G. Jebsen IRC, University of Oslo, Norway; Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: T E
authors.initials: TE
authors.lastname: Mollnes
authors.affiliation: Institute of Clinical Medicine, University of Tromsø - The Arctic University of Norway, Tromsø, Norway; Department of Anesthesiology, Nordland Hospital and University of Nordland, Bodø, Norway.
authors.forename: E W
authors.initials: EW
authors.lastname: Nielsen
authors.affiliation: Institute of Clinical Medicine, University of Tromsø - The Arctic University of Norway, Tromsø, Norway; Department of Laboratory Medicine, Nordland Hospital, Bodø, Norway.
authors.forename: O L
authors.initials: OL
authors.lastname: Brekke
mesh_terms: D000328:Adult; D001777:Blood Coagulation; D001792:Blood Platelets / Q000378:metabolism; D050718:Complement C1 Inhibitor Protein / Q000378:metabolism*; D004926:Escherichia coli / Q000502:physiology*; D004927:Escherichia coli Infections / Q000097:blood*; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D013916:Thrombelastography
chemical_list: D050718:Complement C1 Inhibitor Protein
keywords: Blood coagulation; C1-inhibitor protein; Complement; Escherichia coli; Platelet function test; Thromboelastometry