A Landsem1, H Fure2, T E Mollnes3, E W Nielsen4, O L Brekke5. 1. 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. 2. Research Laboratory, Nordland Hospital, Bodø, Norway. 3. 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. 4. 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. 5. Institute of Clinical Medicine, University of Tromsø - The Arctic University of Norway, Tromsø, Norway; Department of Laboratory Medicine, Nordland Hospital, Bodø, Norway.
Abstract
INTRODUCTION: 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. MATERIALS AND 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.
INTRODUCTION: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. MATERIALS AND 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.