Quantification of the effects of thrombin activatable fibrinolysis inhibitor and α2-antiplasmin on fibrinolysis in normal human plasma

Vance G. Nielsen, Truitt C. Ellis

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)29-33
Number of pages5
JournalBlood Coagulation and Fibrinolysis
Volume18
Issue number1
DOIs
StatePublished - Jan 1 2007

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Keywords

  • Fibrinolysis
  • Thrombelastography
  • Thrombin activatable fibrinolysis inhibitor
  • Tissue type plasminogen activator
  • α-antiplasmin

ASJC Scopus subject areas

  • Hematology

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