C1-inhibitor efficiently delays clot development in normal human whole blood and inhibits Escherichia coli-induced coagulation measured by thromboelastometry. Issue 143 (July 2016)

• Record Type: Journal Article
• Authors: Landsem, A.; Fure, H.; Mollnes, T.E.; Nielsen, E.W.; Brekke, O.L.
• Is Part Of: Thrombosis research. Issue 143(2016)
• Page Start: 63
• Page End: 70
• Publication Date: 2016-07
• Subjects: aPTT activated partial thromboplastin time -- C1-INH C1-inhibitor -- E. coli Escherichia coli -- EXTEM extrinsic thromboelastometry -- HAE hereditary angioedema -- HSA human serum albumin -- INTEM intrinsic thromboelastometry -- LI lysis index -- min minute -- NATEM non-activated thromboelastometry -- PBS phosphate buffered saline -- ROTEM rotational thromboelastometry -- tPA tissue plasminogen activator -- TF tissue factor; Blood coagulation -- Complement -- C1-inhibitor protein -- Escherichia coli -- Platelet function test -- Thromboelastometry; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2016.04.024
• Languages: English
• ISSNs: 0049-3848

Abstract

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 47.6 μM) 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 789 s 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 261 s to 595 s ( p < 0.05). E. coli significantly reduced the NATEM CT after 120 min 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 (47.6 μM) 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. Highlights: C1-INH has anticoagulant effects in human whole blood. C1-INH abolished E.coli -induced coagulation measured as NATEM CT. C1-INH at very high doses inhibited fibrinolysis analysed using Rotem.