Structural changes in fibrin clot associated with the proteolytic activity induced by tissue type plasminogen activator. An NMR study.

ABSTRACT

The kinetic behavior of fibrin clot lysis as induced by tissue-type plasminogen activator (t-PA) was studied using proton magnetic resonance (PMR) and a release assay of fibrin labeled with technetium-99m isotope (99mTc). The lysis pattern of the preformed clot was examined as a function of gradual changes in the amounts of added t-PA and deactivated t-PA. The behavior of fibrinolysis was found to depend strongly on the amount of t-PA in the assay, which markedly affects the lysis rate of fibrin. The changes induced by the lysis were reflected in pronounced prolongation of the transverse relaxation time. The PMR and the radioisotope release measurements point to the possibility that at least two steps are involved in the mechanism of lysis. The PMR seems to be associated with structural features of the clot and reflects the liberation of compartmentalized water from the clot, while the 99mTc analysis reflects the further fragmentation of fibrin.