Abstract
Background and aim. Recent in vitro studies have shown that fibrinolytic activity may be attenuated by a thrombin-activatable fibrinolysis inhibitor (TAFI), which is activated by thrombin, generated via the intrinsic pathway of coagulation in a factor XI-dependent manner. These results indicate that factor XI may play a role in the regulation of endogenous fibrinolysis. The aim of this study was to investigate the effect of in vivo inhibition of factor XI and TAFI in an experimental thrombosis model in rabbits. Methods. Standard I25l-fibrinogen labeled thrombi were preformed in jugular veins of New Zealand rabbits. Thrombi were formed from blood that was preincubated with either a polyclonal goat-anti-rabbit factor XI antibody (0.1 mg/ml) or a control antibody. Experiments were performed with subsequent systemic administration of either the anti-factor XI antibody ( 1 or 7.5 mg/kg) or the control antibody. Endogenous thrombolysis at 2 hours after thrombus formation was assessed by measuring the decrease in I2?l-fibrinogen in the clot. Results. Incorporation of anti-factor XI antibody in jugular vein thrombi in the absence of systemic anti-factor XI antibody resulted in an almost twofold increase in endogenous thrombolysis ( 11.3% ±0.9 vs 6.3% ±0.6 in controls, p < 0.05). A similar effect was observed when the anti-factor XI antibody was administered systemically: 12.1% ±0.8 (1 mg/kg anti-factor XI antibody) or 15.3% ±1.4% (7.5 mg/kg antifactor XI antibody). The systemic administration of I mg/kg or 7.5 mg/kg anti-factor XI antibodies to rabbits resulted in a reduction of plasma factor XI activity of 15% and 80% respectively. Inhibition of TAFI activity also resulted in a twofold increase in clot lysis whereas inhibition of both factor XI and TAFI did not result in an additional effect. Conclusion. The present study provides the first in vivo evidence for enhanced thrombolysis through inhibition of clotting factor XI or inhibition of thrombinactivalable fibrinolysis inhibitor (TAFI), thereby demonstrating a novel role for the intrinsic pathway of coagulation. In vivo, factor XI may rather act as an inhibitor of fibrinolysis than as a coagulation factor.
Original language | English |
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Pages (from-to) | 18 |
Number of pages | 1 |
Journal | Fibrinolysis and Proteolysis |
Volume | 12 |
Issue number | SUPPL. 1 |
Publication status | Published - 1998 |