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[Serial changes in hemostatic molecular markers after urokinase therapy of acute myocardial infarction]
1Department of Medicine, School of Medicine, Keio University.
Insights
Urokinase administration in acute myocardial infarction patients significantly enhanced fibrinolytic activity. Higher urokinase doses profoundly reduced alpha 2-plasmin inhibitor, increasing fibrinolysis markers.
Area of Science:
- Cardiology
- Hematology
- Pharmacology
Context:
- Acute myocardial infarction (AMI) is a critical condition requiring prompt reperfusion therapy.
- Fibrinolysis plays a key role in dissolving blood clots, crucial for restoring blood flow.
- Urokinase is a thrombolytic agent used to treat AMI.
Purpose:
- To investigate the impact of urokinase administration on fibrinolysis in AMI patients.
- To evaluate the effectiveness of different urokinase dosages using novel molecular markers and classical hemostatic tests.
- To assess the changes in fibrinolytic activity and related markers over time following urokinase therapy.
Summary:
- Patients with AMI received urokinase (960,000–1,440,000 units).
- Fibrinolytic activity was assessed using alpha 2-plasmin inhibitor (alpha 2-PI), plasminogen, alpha 2-PI plasmin complex (PIC), FDP D-dimer, prothrombin time (PT), and fibrinogen levels.
- Initial lower-dose IV urokinase showed limited fibrinolytic enhancement, while higher-dose intracoronary urokinase significantly increased fibrinolysis, marked by reduced alpha 2-PI and elevated FDPs.
Impact:
- Demonstrates that higher doses of urokinase are more effective in enhancing fibrinolysis in AMI.
- Highlights the utility of molecular markers like alpha 2-PI in monitoring thrombolytic therapy effectiveness.
- Provides insights into the dynamics of fibrinolysis following urokinase treatment, informing clinical practice for AMI management.
Abstract:
We have examined the changes in fibrinolysis after urokinase administration for 6 patients with acute myocardial infarction. Patients were treated with urokinase with doses between 960,000 and 1,440,000 units, and fibrinolytic activities were determined by using newly developed molecular markers: alpha 2-plasmin inhibitor (alpha 2-PI), plasminogen, alpha 2-PI plasmin complex (PIC) and FDP D dimer. We also used classical hemostatic tests such as prothrombin time (PT) and plasma fibrinogen level. These tests were measured with 1 to 2 hour intervals, during the first 6 hours of therapy, daily during the next 3 days, and subsequently on day 7 and 14. The initial intravenous administration of urokinase with a dose of 460,000 units produced a significant decrease in alpha 2-PI level, but induced only minimal changes in the level of fibrinogen, FDP-E, and FDP D-dimer, suggesting that enhancement of fibrinolytic activity was less pronounced under such therapy. This might be due to the ability of residual amounts of alpha 2-PI to sufficiently inhibit plasmin generation in the circulating blood. However, a subsequent injection of 960,000 units of urokinase into the coronary artery induced a profound reduction in the alpha 2-PI to an unmeasurable level, and resulted in a marked enhancement of fibrinolytic activity. The elevation of FDP-E and FDP D-dimer was accompanied with this decrease in alpha 2-PI and persisted for more than 6 hours after urokinase injection. Prolongation of PT due to decrease in fibrinogen level was also observed over 6 hours.(ABSTRACT TRUNCATED AT 250 WORDS)