Absence of paradoxical thrombin activation by fibrin-specific thrombolytics in acute myocardial infarction: Comparison of single-bolus tenecteplase and front-loaded alteplase

• Published in: Thrombosis research 2002-04, Vol.106 (2), p.113-119
• Main Authors: Szabo, Sebastian, Letsch, Ronald, Ehlers, Raila, Walter, Thomas, Kazmaier, Silke, Helber, Uwe, Hoffmeister, Hans Martin
• Format: Article
• Language: English
• Subjects: Aged; alpha-2-Antiplasmin; Anticoagulants - administration & dosage; Anticoagulants - therapeutic use; Antifibrinolytic Agents - blood; Antithrombin III - analysis; Aspirin - administration & dosage; Aspirin - therapeutic use; Biological and medical sciences; Biomarkers; Blood. Blood coagulation. Reticuloendothelial system; Cardiology. Vascular system; Coronary heart disease; Enzyme Activation - drug effects; Factor XIIa - analysis; Female; Fibrin - drug effects; Fibrin Fibrinogen Degradation Products - analysis; Fibrin specificity; Fibrinolysin; Fibrinolysis - drug effects; Fibrinolytic Agents - pharmacology; Heart; Hemostasis - drug effects; Heparin - administration & dosage; Heparin - therapeutic use; Humans; Male; Medical sciences; Middle Aged; Myocardial infarction; Myocardial Infarction - blood; Myocardial Infarction - drug therapy; Peptide Fragments - blood; Pharmacology. Drug treatments; Platelet Aggregation Inhibitors - administration & dosage; Platelet Aggregation Inhibitors - therapeutic use; Procoagulatory effects; Prothrombin; Recombinant Proteins - administration & dosage; Recombinant Proteins - pharmacology; Recombinant Proteins - therapeutic use; Substrate Specificity; Tenecteplase; Thrombin - drug effects; Thrombolysis; Thrombolytic Therapy; Tissue Plasminogen Activator - administration & dosage; Tissue Plasminogen Activator - blood; Tissue Plasminogen Activator - pharmacology; Tissue Plasminogen Activator - therapeutic use
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/S0049-3848(02)00084-1

Objectives: Thrombolytic therapy in patients with acute myocardial infarction is hampered by bleeding complications and procoagulant effects favoring early reocclusion. TNK-tPA was shown in vitro to have considerable fibrin specificity. We investigated the effects of tenecteplase (TNK-tPA) and alteplase (rt-PA) on the haemostasis and fibrinolytic system. Methods and Results: We enrolled 30 patients with AMI into the study. Twenty patients received front-loaded rt-PA up to 100 mg; 10 patients were given TNK-tPA in a single bolus up to 50 mg. All patients received aspirin and intravenous heparin. During the first 2 days, the following parameters were repetitively determined: thrombin–antithrombin III complexes (TAT), antithrombin III (ATIII), prothrombin fragment F 1+2 (F 1+2), kallikrein-like activity (KK), activated factor XII (FXIIa), plasmin alpha 2–antiplasmin complexes (PAP), fibrinogen, D-dimers (DD), tissue-type plasminogen activator (t-PA). A total of 75 healthy persons served as control group. TAT increased significantly after rt-PA but not after TNK-tPA (3 h: 38.1±29.4 versus 10.5±4.2 μg/l; p