Fibrin specificity and procoagulant effect related to the kallikrein-contact phase system and to plasmin generation with double-bolus reteplase and front-loaded alteplase thrombolysis in acute myocardial infarction

• Published in: The American journal of cardiology 2000-08, Vol.86 (3), p.263-268
• Main Authors: Hoffmeister, Hans Martin, Kastner, Christof, Szabo, Sebastian, Beyer, Martin E, Helber, Uwe, Kazmaier, Silke, Baumbach, Andreas, Wendel, Hans Peter, Heller, Wolfgang
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antithrombin III - drug effects; Antithrombin III - metabolism; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Fibrin - drug effects; Fibrin - metabolism; Fibrinolysin - metabolism; Fibrinolysis - drug effects; Fibrinolytic Agents - administration & dosage; Fibrinolytic Agents - adverse effects; Hemostasis - drug effects; Humans; Kallikreins - drug effects; Kallikreins - metabolism; Male; Medical sciences; Middle Aged; Myocardial Infarction - blood; Myocardial Infarction - drug therapy; Peptide Hydrolases - drug effects; Peptide Hydrolases - metabolism; Pharmacology. Drug treatments; Prospective Studies; Recombinant Proteins - administration & dosage; Recombinant Proteins - adverse effects; Recurrence; Thrombin - metabolism; Thrombolytic Therapy; Tissue Plasminogen Activator - administration & dosage; Tissue Plasminogen Activator - adverse effects
• ISSN: 0002-9149; 1879-1913
• DOI: 10.1016/S0002-9149(00)00911-5

This study was undertaken to compare the effects of reteplase and alteplase regimens on hemostasis and fibrinolysis in acute myocardial infarction (AMI). Thrombolytic treatment in patients with AMI is hampered by paradoxical procoagulant effects that favor early reocclusion. In vivo data comparing this effect and the fibrin specificity of double-bolus reteplase and front-loaded alteplase regimens are not available. In a prospective, randomized study, 50 patients with AMI were either treated with double bolus (10 + 10 U) reteplase or with front-loaded alteplase (up to 100 mg) within 6 hours of symptom onset. Thirty apparently healthy persons served as controls. Molecular markers of coagulation and fibrinolysis were serially examined for up to 5 days. Paradoxical thrombin activation at 3 hours after initiation of therapy was comparable between reteplase and alteplase. Reteplase (65 ± 5 U/L) and alteplase (72 ± 8 U/L) caused significantly elevated kallikrein activity at 3 hours after adminstration (p