title: Late activation of the fibrinolytic system in myocardial infarction treated with thrombolytic therapy. Influence of the coronary anatomical substrate.
abstract: Procoagulant activity, thrombin and fibrinolytic system activation have been demonstrated in the first 24-48 h after acute myocardial infarction treated with thrombolytic therapy. Little is known about what happens in the subsequent days, during which the incidence of ischaemic recurrence is high. In 21 patients treated with streptokinase and in 20 patients treated with urokinase we evaluated, with multiple plasma determinations, D-dimer and fibrinogen plasma levels in the first week after myocardial infarction. From the 2nd hour after the beginning of thrombolysis 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 subsequently substituted for the intravenous route. Coronary angiography was performed 7 days after infarction. From the basal values 2.22 +/- 1.44 nmol.1(-1) in the streptokinase group and 3.28 +/- 3.05 nmol.1(-1) in the urokinase group, D-dimer rose consistently in the 1st hour after thrombolysis 269.4 +/- 206.7 nmol.1(-1) and 44.5 +/- 35.5 nmol.1(-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-dimer slowly decreased during the study period. It reverted to normal values only in 10/21 patients in the streptokinase group; in the urokinase group normalization was attained in 14/20 patients between the 3rd and 6th days. After withdrawal of i.v. heparin in patients of both groups 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 with TIMI 2 or 3 grade coronary flow, D-dimer showed a monophasic pattern 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 active and persistent fibrin degradation more marked and lasting after streptokinase than after urokinase. When occurring sooner, it is a consequence of plasmin activation induced by thrombolytic agents; later it seems to be related to intracoronary substrate, as suggested by the relationship of plasma elevation of D-dimer with the presence of occluded or suboccluded infarction-related vessels.
authors.affiliation: Istituto di Cardiologia dell'Università degli Studi, Fondazione Monzino, IRCCS, Milano, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Salvioni
authors.forename: G B
authors.initials: GB
authors.lastname: Perego
authors.forename: G
authors.initials: G
authors.lastname: Marenzi
authors.forename: G
authors.initials: G
authors.lastname: Lauri
authors.forename: F
authors.initials: F
authors.lastname: Giraldi
authors.forename: S
authors.initials: S
authors.lastname: Grazi
authors.forename: M D
authors.initials: MD
authors.lastname: Guazzi
mesh_terms: D000368:Aged; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005340:Fibrinogen / Q000032:analysis; D005342:Fibrinolysis / Q000502:physiology*; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D010960:Plasminogen Activators / Q000627:therapeutic use; D013300:Streptokinase / Q000627:therapeutic use; D015912:Thrombolytic Therapy; D013997:Time Factors; D014568:Urokinase-Type Plasminogen Activator / Q000627:therapeutic use
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D005343:Fibrinolytic Agents; D005340:Fibrinogen; D013300:Streptokinase; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator