The mechanism of in vitro clot lysis induced by vascular plasminogen
activator
C Tran-Thang, EK Kruithof and F Bachmann
The contribution of vascular plasminogen activator (v-PA) to the lysis of
whole blood and plasma clots was investigated. v-PA released into the
circulation after infusion of deamino-D-arginine vasopressin (DDAVP) was
shown to bind quantitatively to plasma clots. Its apparent molecular
weight, determined by the SDS-PAGE fibrin-agarose underlay method, was
approximately 68,000 daltons, and its activity was quenched by antibodies
against human tissue plasminogen activator (t-PA). Clots prepared from
post-DDAVP plasma or post-DDAVP whole blood, rich in v- PA, did not lyse
when incubated in imidazole buffer or normal plasma, as determined by the
release of 125I from radiolabeled clots. However, clots made of v-PA-poor
plasma or whole blood, incubated in v-PA-rich plasma, underwent substantial
lysis. The concentration of PA in clots incubated in v-PA-rich plasma
progressively increased in relation to the initial concentration of v-PA in
the surrounding plasma. The results suggest that, at low concentrations of
circulating v-PA, a hemostatic plug will lyse at a very low rate. However,
when the v-PA concentration in the clot environment is increased, v-PA will
accumulate progressively onto fibrin and induce thrombolysis.
Volume 63,
Issue 6,
pp. 1331-1337,
06/01/1984
Copyright © 1984 by The American Society of Hematology
