title: Quantification of the effects of thrombin activatable fibrinolysis inhibitor and alpha2-antiplasmin on fibrinolysis in normal human plasma.
abstract: Two major proteins that inhibit fibrinolysis include thrombin activatable fibrinolysis inhibitor (TAFI) and alpha2-antiplasmin. Our goal was to quantify the contribution of TAFI and alpha2-antiplasmin to antifibrinolytic defenses with thrombelastography. Plasma activated with tissue factor/kaolin was subjected to fibrinolysis with tissue-type plasminogen activator (100 U/ml). Prior to activation, TAFI activity was inhibited with either potato carboxypeptidase inhibitor (25 microg/ml) or an anti-TAFI antibody, and alpha2-antiplasmin activity was inhibited with an anti-alpha2-antiplasmin antibody. Data were collected for 30 min, with the time of onset and rate of fibrinolysis determined. Compared with uninhibited samples, TAFI inhibition significantly (P < 0.05) decreased the time of onset of fibrinolysis by 70% and increased the rate of lysis by 70%. There was no difference between potato carboxypeptidase inhibitor and anti-TAFI antibody inhibition. Inhibition of alpha2-antiplasmin resulted in a significantly (P < 0.05) decreased time of onset (85%) and increased the rate of lysis (557%) compared with uninhibited samples. Inhibition of alpha2-antiplasmin activity resulted in a significantly (P < 0.05) greater fibrinolytic response than TAFI inhibition. In conclusion, utilization of standard inhibitors and thrombelastography permitted quantification of the effects of TAFI and alpha2-antiplasmin on fibrinolysis in plasma. Future investigation of diseases involving hypofibrinolysis (e.g. left ventricular assist devices) could be conducted using this assay system.
authors.affiliation: Department of Anesthesiology, The University of Alabama at Birmingham, Alabama 35249-6810, USA. vnielsen@uab.edu
authors.forename: Vance G
authors.initials: VG
authors.lastname: Nielsen
authors.forename: Truitt C
authors.initials: TC
authors.lastname: Ellis
mesh_terms: D000906:Antibodies; D001773:Blood Cells / Q000187:drug effects; D001777:Blood Coagulation; D025901:Carboxypeptidase B2 / Q000032:analysis / Q000276:immunology / Q000494:pharmacology*; D002478:Cells, Cultured; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D008722:Methods; D010940:Plant Proteins; D011480:Protease Inhibitors; D013916:Thrombelastography; D000979:alpha-2-Antiplasmin / Q000032:analysis / Q000276:immunology / Q000494:pharmacology*
chemical_list: D000906:Antibodies; D010940:Plant Proteins; D011480:Protease Inhibitors; D000979:alpha-2-Antiplasmin; D025901:Carboxypeptidase B2