Procoagulant effects of thrombolytic therapy in acute myocardial infarction.
OBJECTIVE
To examine the procoagulant effects of thrombolytic agent on hemostasis and study the role of hemostatic markers as predictors of clinical outcomes.


METHODS
In the present study, eighteen patients with acute myocardial infarction (AMI) received 1.5 or 2.0 million U nonspecific urokinase (UK), or 70 approximately 80 mg fibrin-specific recombinant tissue plasminogen activator (rt-PA) and did not use heparin until 8 hours after intravenous injection of the above agents. Eight patients with AMI and without thrombolytic therapy were enrolled as controls. Coagulant and thrombolytic activity markers included thrombin-antithrombin III complex (TAT), D-dimer, fibrinogen (Fg), FMPV/Amax. All markers were determined before, immediately, 1, 2, 4 and 8 hours after the administration of thrombolytic agents respectively.


RESULTS
Molecular marker of thrombin generation--TAT showed an activated coagulant state immediately after thrombolytic therapy. Level of TAT showed no significant changes between every two observed phases in controls. However, level of TAT increased significantly from 4.95 +/- 1.75 microg/L ( 4.63 +/- 1.37 microg/L) to 14.71 +/- 3.31 microg/L (14.25 +/- 2.53 microg/L) before and immediately after administration of thrombolytic agents UK (or rt-PA). There was significant difference between level of serum TAT of patients with and without thrombolytic therapy (P < 0.05). Patients achieving clinical reperfusion had lower TAT level than those failing in thrombolytic therapy, and higher FMPV/Amax level than controls. D-dimer, a surrogate of thrombolytic activity increased markedly and Fg significantly declined after thrombolytic therapy (P < 0.05).


CONCLUSIONS
Thrombin generation occurred in plasma in response to excess fibrinolysis induced by thrombolytic therapy. Both urokinase and rt-PA had procoagulant action. This transient activation of the coagulant system might contribute to early reocclusion. These data provided the theoretical support for simultaneous administration of anticoagulant therapy with thrombolytic agents. These results also suggested that TAT might be useful in predicting clinical outcomes of patients treated with thrombolytic therapy for AMI.
Wang
Yanni
Y
Department of Cardiology, the First Hospital, Xi'an Jiaotong University, Xi'an 710061.
Liu
Qianqian
Q
Zhu
Jiaqing
J
Yuan
Zuyi
Z
Ma
Xi
X
D000368:Aged; D000990:Antithrombin III; D015415:Biomarkers / Q000097:blood; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy*; D010447:Peptide Hydrolases / Q000097:blood; D011994:Recombinant Proteins / Q000627:therapeutic use; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D014568:Urokinase-Type Plasminogen Activator / Q000627:therapeutic use*
D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; D000990:Antithrombin III; D005340:Fibrinogen; D010447:Peptide Hydrolases; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator