CHANGES IN FIBRINOGEN AFTER RT-PA ADMINISTRATION

Among patients participating in the TIMI-II protocol, there was a vari ability in the fibrinolytic response to recombinant tissue plasminogen activator (rt-PA). A cohort of 20 TIMI-II patients was selected for d etailed study because their responses to rt-PA varied widely in the de gree of fibrin(ogen)olysis. Patient plasmas were analyzed by immunoblo tting for changes in fibrinogen and plasminogen. Measurements of fibri nogen, fibrinogen degradation product (FDP), D-dimer, B beta 1-42, pla sminogen, and t-PA were also correlated. Three patterns of response to rt-PA were identified: Group A (n = 4) had fibrinogenolysis without f ibrinolysis; Group B (n = 11) had fibrinolysis and mild fibrinogenolys is; and Group C (n = 5) had fibrinolysis with intense fibrinogenolysis . Group C patients also demonstrated qualitative changes in high-molec ular-weight (HMW) and low-molecular-weight (LMW) fibrinogens, whereas Group A and B patients demonstrated only mild alterations in fibrinoge n composition. Plasmin-inhibitor complexes were identified in all thre e groups. All patients had both plasmin-alpha(2)-anti-plasmin and plas min-alpha(2)-macroglobulin complexes at the 50-min time point. The con centration of pretreatment plasminogen correlated with the degree of f ibrinogenolysis.