ENHANCEMENT OF RABBIT JUGULAR-VEIN THROMBOLYSIS BY NEUTRALIZATION OF FACTOR-XI - IN-VIVO EVIDENCE FOR A ROLE OF FACTOR-XI AS AN ANTI-FIBRINOLYTIC FACTOR

Recent in vitro studies have shown that fibrinolytic activity may be a ttenuated by a thrombin-activatable fibrinolysis inhibitor (TAFI), whi ch is activated by thrombin, generated via the intrinsic pathway of co agulation in a factor XI-dependent way, Thus factor XI may play a role in the regulation of endogenous fibrinolysis, The aim of this study w as to investigate the effect of in vivo inhibition of factor XI and TA FI in an experimental thrombosis model in rabbits, Incorporation of an ti-factor XI antibodies in jugular vein thrombi resulted in an almost twofold increase in endogenous thrombolysis compared with a control an tibody, A similar effect was observed when the anti-factor XI antibody was administered systemically, Inhibition of TAFI activity also resul ted in a twofold increase in clot lysis whereas inhibition of both fac tor XI and TAFI activity had no additional effect, Thus, we provide th e first in vivo evidence for enhanced thrombolysis through inhibition of clotting factor XI, demonstrating a novel role for the intrinsic pa thway of coagulation, Furthermore we demonstrate that inhibition of TA FI had a similar effect on thrombolysis, We postulate that inhibition of factor XI activity enhances thrombolysis because of diminished indi rect activation of TAFI.