Bolus Thrombolysis in Venous Thromboembolism (7)

The extent of fibrinogenolysis was quantified by measuring the levels of B01-42, a fibrinogen-derived fragment released by plasmin early in the course of fibrinogen conversion to fragment X. The presence of a clot increased rt-PA-mediated Bp 1-42 release more than 20-fold. Potentiation of fibrinogenolysis is not the result of enhanced plasminogen activation on the clot surface, since Bpi-42 generation continues after the clot is removed from rt-PA-containing plasma. Further, incubation of clot lysates with rt-PA-containing plasma produces a concentration-dependent potentiation of Bp 1-42 release to an extent similar to that produced by an intact clot.
These in vitro studies demonstrate that soluble FDPs augment rt-PA-induced fibrinogenolysis. Thus, cross-linked FDPs derived from the lysis of thrombi, together with fibrin monomer generated during thrombus formation, could activate the rt-PA in circulation when this is continuously present due to prolonged infusion. This concept is supported by the results of studies in experimental animals which demonstrate that rt-PA administration to animals with a thrombus results in significantly more bleeding and fragment X formation than does infusion of the same rt-PA dose in animals without a clot. This circumstance could nullify the advantage of rt-PA (clot selectivity) over streptokinase and urokinase.

Category: Venous Thromboembolism

Tags: thrombolysis, thrombolytic agent, venous thromboembolism