LATE ACTIVATION OF THE FIBRINOLYTIC SYSTEM IN MYOCARDIAL-INFARCTION TREATED WITH THROMBOLYTIC THERAPY - INFLUENCE OF THE CORONARY ANATOMICAL SUBSTRATE

Procoagulant activity, thrombin and fibrinolytic system activation hav e been demonstrated in the first 24-48 h after acute myocardial infarc tion treated with thrombolytic therapy. Little is known about what hap pens in the subsequent days, during which the incidence of ischaemic r ecurrence is high. In 21 patients treated with streptokinase and in 20 patients treated with urokinase we evaluated, with multiple plasma de terminations, D-dimer and fibrinogen plasma levels in the first week a fter myocardial infarction. From the 2nd hour after the beginning of t hrombolysis to the 4th day, all patients received intravenous heparin in doses sufficient to raise the partial thromboplastin time to twice its normal level; subcutaneous calcium heparin (12 000 U/day) was subs equently substituted for the intravenous route. Coronary angiography w as performed 7 days after infarction. From the basal values 2.22 +/- 1 .44 nmol.l(-1) in the streptokinase group and 3.28 +/- 3.05 nmol.l(-1) in the urokinase group, D-dimer rose consistently in the Ist hour aft er thrombolysis 269.4 +/- 206.7 nmol.l(-1) and 44.5 +/- 35.5 nmol.l(-1 ) in the streptokinase and urokinase groups, respectively; P < 0.001. After the peak value, which in both groups was reached after 5 h, D-di mer slowly decreased during the study period. It reverted to normal va lues only in 10/21 patients in the streptokinase group; in the urokina se group normalization was attained in 14/20 patients between the 3rd and 6th days. After withdrawal of i.v. heparin in patients of both gro ups with TIMI 0 or 1 grade of coronary patency, D-dimer rose to levels four to seven times greater than normal; in patients of both groups w ith TIMI 2 or 3 grade coronary flow, D-dimer showed a monophasic patte rn of progressive normalization (P < 0.05 and P < 0.01 at the 6th and 7th days, respectively, for differences between TIMI 0-1 and TIMI 2-3 groups). After myocardial infarction, thrombolysis is followed by acti ve and persistent fibrin degradation more marked and lasting after str eptokinase than after urokinase. When occurring sooner, it is a conseq uence of plasmin activation induced by thrombolytic agents; later it s eems to be related to intracoronary substrate, as suggested by the rel ationship of plasma elevation of D-dimer with the presence of occluded or suboccluded infarction-related vessels.