Article

Quantification of the effects of thrombin activatable fibrinolysis inhibitor and alpha2-antiplasmin on fibrinolysis in normal human plasma.

Department of Anesthesiology, The University of Alabama at Birmingham, Alabama 35249-6810, USA.
Blood Coagulation and Fibrinolysis (Impact Factor: 1.38). 01/2007; 18(1):29-33. DOI: 10.1097/MBC.0b013e3280129afe
Source: PubMed

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.

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