Two major proteins that inhibit fibrinolysis include thrombin activatable fibrinolysis inhibitor (TAFI) and α2-antiplasmin. Our goal was to quantify the contribution of TAFI and α2-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 μg/ml) or an anti-TAFI antibody, and α2-antiplasmin activity was inhibited with an anti-α2-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 α2-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 α2-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 α2-antiplasmin on fibrinolysis in plasma. Future investigation of diseases involving hypofibrinolysis (e.g. left ventricular assist devices) could be conducted using this assay system.
Department of Anesthesiology, The University of Alabama at Birmingham, Birmingham, Alabama, USA
Received 22 May, 2006
Revised 3 August, 2006
Accepted 11 August, 2006
Correspondence and requests for reprints to Vance G. Nielsen, MD, Department of Anesthesiology, The University of Alabama at Birmingham, 901 South 19th Street, Basic Medical Research II, Room 206, Birmingham, AL 35249-6810, USA Tel: +1 205 934 4696; fax: +1 205 934 7437; e-mail: email@example.com
Sponsorship: This investigation was supported by the Department of Anesthesiology.