Summary
Platelet clots resist fibrinolysis by plasminogen activators. We hypothesized that
platelet factor XIII may enhance the fibrinolytic resistance of platelet-rich clots
by catalyzing the crosslinking of α2-antiplasmin (α2AP) to fibrin. Analysis of plasma clot structure by polyacrylamide gel electrophoresis
and immunoblotting revealed accelerated α2AP-fibrin crosslinking in platelet-rich compared with platelet-depleted plasma clots.
A similar study of clots formed with purified fibrinogen (depleted of factor XIII
activity), isolated platelets, and specific factor XIII inhibitors indicated that
this accelerated crosslinking was due to the catalytic activity of platelet factor
XIII. Moreover, when washed platelets were aggregated by thrombin, there was evidence
of platelet factor XIII-mediated crosslinking between platelet α2AP and platelet fibrin(ogen). Specific inhibition (by a monoclonal antibody) of the
α2AP associated with washed platelet aggregates accelerated the fibrinolysis of the
platelet aggregate. Thus in platelet-rich plasma clots, and in thrombin-induced platelet
aggregates, platelet factor XIII actively formed α2AP-fibrin crosslinks, which appeared to enhance the resistance of platelet-rich clots
to fibrinolysis.