Related Experiment Videos
Comparison of thrombolytic agents: selected hematologic, vascular and clinical events
1Department of Medicine, University of Rochester School of Medicine & Dentistry, New York.
Insights
Different plasminogen activators cause similar blood changes and complications, leading to hypocoagulability. Reperfusion rates vary, but antiplatelet agents like aspirin significantly reduce mortality in myocardial infarction.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Pharmacology
Background:
- Plasminogen activators are crucial for thrombolysis but exhibit varied pharmacokinetics.
- Understanding their effects on coagulation and clinical outcomes is vital for acute cardiovascular events.
Purpose of the Study:
- To compare the effects of different plasminogen activators on blood parameters and clinical outcomes.
- To evaluate the impact of these agents on coronary artery reperfusion and reocclusion rates.
Main Methods:
- Review of existing literature on anisoylated plasminogen streptokinase activator complex (APSAC), streptokinase (SK), urokinase (UK), recombinant tissue plasminogen activator (rt-PA), and recombinant single-chain urokinase plasminogen activator (scu-PA).
- Analysis of data on infusion regimens, half-life, hypofibrinogenemia, hypercoagulability, reperfusion, and reocclusion.
- Assessment of the role of adjunctive antiplatelet therapy, such as aspirin.
Main Results:
- All activators induce hypofibrinogenemia via plasmin degradation, with recovery over 48 hours post-discontinuation.
- Reperfusion rates are 50-60% within 3-4 hours; rt-PA shows greater potential than SK for older thrombi.
- Reocclusion occurs in 10-20% of patients, more frequently after rt-PA than SK.
Conclusions:
- Plasminogen activators share similar mechanisms and complications, primarily hypocoagulability.
- Adjunctive aspirin significantly reduces mortality post-myocardial infarction, with APSAC showing maximal benefit.
- Therapeutic strategies should consider activator half-life, reperfusion potential, and the benefits of antiplatelet agents.
Abstract:
Plasminogen activators of distinct structure and biochemical action seem to be more equivalent than unique regarding induced blood changes and clinical complications. All of the activators ultimately degrade substrate through plasmin, resulting in a striking hypocoagulable state characterized primarily by a decrease in fibrinogen concentration. Infusion regimens are inversely proportional to the half-life of the activator, which is relatively long with anisoylated plasminogen streptokinase activator complex (APSAC), intermediate for streptokinase (SK) and urokinase (UK), and very short for recombinant tissue plasminogen activator (rt-PA) and recombinant single-chain urokinase plasminogen activator (scu-PA). After therapy is discontinued, hypofibrinogenemia persists until activator is cleared from the blood, then is slowly corrected over 48 hours, regardless of which thrombolytic agent has been used. Coagulation and platelet activity may be transiently accentuated soon after administration of the agent. Hypercoagulability contributes to vascular reocclusion, especially when acting in concert with the thrombogenic influences of residual thrombus and the original ruptured atherosclerotic plaque. In the first 3 to 4 hours after symptom onset, coronary artery reperfusion can be achieved with all of the thrombolytic agents in 50 to 60% of patients, with a greater thrombolytic potential of rt-PA over SK in thrombi of greater than 4 hours' duration. After coronary artery reperfusion, reocclusion occurs in 10 to 20% of patients, more often after rt-PA than SK treatment. Antiplatelet agents such as aspirin decrease the incidence of reocclusion and when added to either SK or rt-PA, decrease mortality after acute myocardial infarction by half. APSAC appears to have a maximal beneficial effect in reducing mortality even without aspirin.(ABSTRACT TRUNCATED AT 250 WORDS)