Comparison of streptokinase, urokinase, and recombinant tissue plasminogen activator in an in vitro model of venous thrombolysis.
OBJECTIVE
Presumed differences in the thrombolytic activity and fibrinolytic specificity of the three commonly used thrombolytic agents, streptokinase, urokinase, and recombinant tissue plasminogen activator (rt-PA), are based on clinical study results, where variability renders meaningful comparisons difficult. An in vitro model of catheter-directed venous thrombolysis was used to compare the three agents.


METHODS
Retracted iodine 125-radiolabeled clots that simulate those observed in the venous system were infused with thrombolytic agents at doses analogous to those used clinically. Perfusion with heparinized, whole human blood was undertaken for 60 minutes, measuring the efficacy of thrombolysis through serial quantification of radio tracer released into the circuit. Fibrinolytic specificity was determined by following decrements in perfusate fibrinogen concentration.


RESULTS
Streptokinase was the agent associated with the slowest rate of clot lysis (p = 0.01 vs urokinase and rt-PA). Urokinase was associated with an intermediate rate of lysis but appeared to be the agent with the greatest degree of fibrinolytic specificity (p = 0.02 vs streptokinase, p = 0.05 vs rt-PA). Although rt-PA was associated with improved efficacy early in the perfusions, the differences between rt-PA and urokinase dissipated after 30 minutes.


CONCLUSIONS
These laboratory observations suggest that urokinase may be the most appropriate agent for catheter-directed venous thrombolysis, offering an advantageous compromise between fibrinolytic specificity and thrombolytic speed.
D000704:Analysis of Variance; D003018:Clot Retraction; D003365:Costs and Cost Analysis; D005340:Fibrinogen; D006801:Humans; D066298:In Vitro Techniques; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000191:economics; D013300:Streptokinase / Q000008:administration & dosage* / Q000191:economics; D013917:Thrombin; D015912:Thrombolytic Therapy / Q000191:economics / Q000379:methods*; D013924:Thrombophlebitis / Q000139:chemically induced / Q000188:drug therapy* / Q000191:economics; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000191:economics; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage* / Q000191:economics
D011994:Recombinant Proteins; D005340:Fibrinogen; D013300:Streptokinase; D013917:Thrombin; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator