CROSS-LINKING OF ALPHA(2)-ANTIPLASMIN TO FIBRIN IS A KEY FACTOR IN REGULATING BLOOD-CLOT LYSIS - SPECIES-DIFFERENCES

The basal lysis rates of ex-vivo prepared blood clots from rats, mice, hamsters, dogs, and humans and levels of alpha(2)-antiplasmin (alpha( 2)-AP) cross-linked to fibrin have been studied in the presence and ab sence of factor XIII (FXIII) inhibitors using a brood clot lysis assay and an alpha(2)-AP binding assay. Clots prepared from rat or human bl ood lysed spontaneously within 3-5 h. Clots from hamster blood lysed c ompletely within 30 min but clots prepared from murine or canine blood lysed only after addition of 1.0 IU human t-PA. To study the effect o f activated FXIII (FXIII(a)) inhibition blood clot lysis the FXIII inh ibitors L722151 and mono-dansylcadaverine (dansyl) were used. In the p resence of the FXIII inhibitors human, murine, and canine blood clots showed increased lysis rates. The lysis rate of rat blood clots was no t affected. Effects on hamster blood clots could not be detected becau se of the high basal lysis rate. In clots prepared from human, murine, or canine plasma about 20% of the plasma alpha(2)-AP concentration wa s cross-linked to fibrin. FXIII, inhibitors inhibited crosslinking by more than 80%. No significant cross-linking of alpha(2)-AP could be de tected in rat and hamster plasma clots. When 0.1 volume of human plasm a was added to 0.9 volume of rat plasma the level of alpha(2)-AP cross -linking was equal to that in human plasma indicating that rat alpha(2 )-AP can be cross-linked to human fibrin. The same effect was obtained with human FXIII deficient plasma but not with human fibrinogen defic ient plasma. These experiments indicate that rat fibrinogen is not a s ubstrate for the cross-linking of rat alpha(2)-AP catalysed by rat FXI II(a). Addition of human plasma to hamster plasma did not result in an increased level of alpha(2)-AP cross-linking which indicates that oth er factors are involved.