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


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 microg/l; p < 0.01), indicating paradoxical thrombin activation. F 1 + 2 increased transiently after rt-PA but not after TNK-tPA. Fibrinogen was significantly lower after rt-PA versus TNK-tPA (3 h: 163 +/- 27 versus 380 +/- 54 mg/dl; p < 0.05). KK activities in the rt-PA group were significantly (p < 0.01) increased over 48 h versus TNK-tPA. PAP and D-dimers were lower over the time course of 48 h in the tenecteplase group versus rt-PA.


CONCLUSIONS
This study indicates that tenecteplase has higher fibrin specificity not only in vitro but also in vivo versus alteplase. TNK-tPA consecutively has no paradoxical systemic procoagulant effect due to the lower extent of activation of the kallikrein-factor XII system than alteplase.
Medizinische Klinik II, Städtisches Klinikum Solingen, Gotenstr 1, 42653 Solingen, Germany. KrisztinaSzb@aol.com
Sebastian
S
Szabo
Ronald
R
Letsch
Raila
R
Ehlers
Thomas
T
Walter
Silke
S
Kazmaier
Uwe
U
Helber
Hans Martin
HM
Hoffmeister
D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use; D000933:Antifibrinolytic Agents / Q000097:blood; D000990:Antithrombin III / Q000032:analysis; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use; D015415:Biomarkers; D004789:Enzyme Activation / Q000187:drug effects; D015956:Factor XIIa / Q000032:analysis; D005260:Female; D005337:Fibrin / Q000187:drug effects*; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005341:Fibrinolysin; D005342:Fibrinolysis / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006487:Hemostasis / Q000187:drug effects; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000188:drug therapy; D010446:Peptide Fragments / Q000097:blood; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D011516:Prothrombin; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013379:Substrate Specificity; D000077785:Tenecteplase; D013917:Thrombin / Q000187:drug effects*; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D000979:alpha-2-Antiplasmin
D000925:Anticoagulants; D000933:Antifibrinolytic Agents; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D005343:Fibrinolytic Agents; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; D000979:alpha-2-Antiplasmin; C036309:fibrin fragment D; C037742:plasmin-plasmin inhibitor complex; C045879:prothrombin fragment 1.2; D000990:Antithrombin III; D011516:Prothrombin; D005337:Fibrin; D006493:Heparin; D015956:Factor XIIa; D013917:Thrombin; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D001241:Aspirin; D000077785:Tenecteplase