Cross-linking of α2-antiplasmin to fibrin is a key factor in regulating blood clot lysis

Abstract

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 absence of factor XIII (FXIII) inhibitors using a blood clot lysis assay and an alpha 2-AP binding assay. Clots prepared from rat or human blood lysed spontaneously within 3-5 h. Clots from hamster blood lysed completely 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 of activated FXIII (FXIIIa) inhibition on blood clot lysis the FXIII inhibitors L722151 and mono-dansylcadaverine (dansyl) were used. In the presence of the FXIII inhibitors human, murine, and canine blood clots showed increased lysis rates. The lysis rate of rat blood clots was not affected. Effects on hamster blood clots could not be detected because of the high basal lysis rate. In clots prepared from human, murine, or canine plasma about 20% of the plasma alpha 2-AP concentration was cross-linked to fibrin. FXIII inhibitors inhibited cross-linking by more than 80%. No significant cross-linking of alpha 2-AP could be detected in rat and hamster plasma clots. When 0.1 volume of human plasma 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.(ABSTRACT TRUNCATED AT 250 WORDS)