Does albumin play a role in fibrinolysis by its inhibition of plasminogen activation?

One of the clinical characteristics of patients with nephrotic syndrome is hypoalbuminemia. The mechanism underlying the susceptibility to thrombosis in this group of patients is not fully understood. The hypoalbuminemia may alter the structure of fibrin clots and affect clot lysis, thereby influencing the coagulolytic balance. In the present study, we investigated the effect of albumin on fibrinolysis. The effect of albumins from several manufacturers and recombinant albumin on the plasminogen activation were tested in an in vitro assay. A chromogenic substrate highly selective for plasmin was used to detect the generation of plasmin. This study revealed a dose-dependent inhibition of plasminogen activation by albumin in a concentration range between 12.5 g/L and 50 g/L. The percentage of inhibition at maximum plasmin activity was different for each albumin, varying from 23% to 90%. Pre-incubation of albumin with fibrinogen enhanced the inhibition, suggesting that by binding to fibrin(ogen) albumin may hinder the formation of the ternary complex and thereby interfere in the fibrinolytic process. This may have consequences for patients with nephrotic syndrome, whose low albumin levels may provide a mechanism partially compensating the well-known hypercoagulability.