Changes in Fibrinogen After rt-PA Administration

Abstract

Among patients participating in the TIMI-II protocol, there was a variability in the fibrinolytic re sponse to recombinant tissue plasminogen activator (rt- PA). A cohort of 20 TIMI-II patients was selected for detailed study because their responses to rt-PA varied widely in the degree of fibrin(ogen)olysis. Patient plasmas were analyzed by immunoblotting for changes in fibrino gen and plasminogen. Measurements of fibrinogen, fibrin ogen degradation product (FDP), D-dimer, Bβ 1-42, plas minogen, and t-PA were also correlated. Three patterns of response to rt-PA were identified: Group A ( n = 4) had fibrinogenolysis without fibrinolysis; Group B ( n = 11) had fibrinolysis and mild fibrinogenolysis; and Group C ( n = 5) had fibrinolysis with intense fibrinogenolysis. Group C patients also demonstrated qualitative changes in high- molecular-weight (HMW) and low-molecular-weight (LMW) fibrinogens, whereas Group A and B patients demonstrated only mild alterations in fibrinogen compo sition. Plasmin-inhibitor complexes were identified in all three groups. All patients had both plasmin-α2-anti plasmin and plasmin-α2-macroglobulin complexes at the 50-min time point. The concentration of pretreatment plasminogen correlated with the degree of fibrinogenoly sis.