Compaction of fibrin clots reveals the antifibrinolytic effect of factor XIII: comment

Abstract

The interesting article on the antifibrinolytic effect of factor XIII by Rijken et al.[1] was predicated on the assumption that fibrinolysis is mediated only by tissuetype plasminogen activator (t-PA), as that is what was studied. However, there is evidence that this common assumption should be questioned.In a study published almost 30 years ago, we showed that, whereas spontaneous lysis of platelet-poor plasma clots was mediated by t-PA, that of platelet-rich plasma clots, with which this article was concerned, could not be abolished by t-PA antibody, but instead was abolished by the addition of urokinase plaminogen activator (u-PA) antibody. Furthermore, evidence was found that endogenous t-PA promoted the effect of endogenous u-PA, indicating that both activators were involved in endogenous fibrinolysis [2]. Since that time, platelets [3,4] and monocytes [5] have been shown to be carriers of u-PA.In t-PA and u-PA knockout studies, t-PA knockout was not associated with spontaneous fibrin formation, in contrast to u-PA knockout [6], and it also did not inhibit lysis of an intravascular thrombus [7]. In these two studies, eliminating both genes had a major effect on fibrinolysis. The findings are consistent with both activators being involved in endogenous lysis, although u-PA rather than t-PA had the dominant effect.The fact that the level of D-dimer is normally 112-250 ng mL À1 rather than zero provides evidence that endogenous fibrinolysis is an ongoing physiologic process. It is unlikely that t-PA alone, most of which is in an inhibitor complex, can account for this fibrinolytic effect. Therefore, the findings in the above original study, although relevant to t-PA-mediated lysis, cannot be assumed to apply to endogenous fibrinolysis. Disclosure of Conflict of InterestsThe author states that he has no conflict of interest.

Compaction of fibrin clots reveals the antifibrinolytic effect of factor XIII: reply

“…We thank Dr Gurewich for his critical evaluation of the impact of our recently published article on factor XIII (FXIII) . This article reports that mechanical compaction or platelet‐mediated retraction of plasma clots is essential to fully reveal the antifibrinolytic effect of FXIII on tissue‐type plasminogen activator (t‐PA)‐induced plasma clot lysis.…”