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Published on: March 19, 2018
The platelet-related effects of tenecteplase versus alteplase versus reteplase
Paul A Gurbel1, Kevin Hayes, Kevin P Bliden
1Sinai Center for Thrombosis Research, 2401 West Belvedere Avenue, Baltimore, MD 21215, USA. pgurbel@lifebridgehealth.org
Insights
Alteplase demonstrates significant antiplatelet properties, inhibiting aggregation more effectively than tenecteplase or reteplase. This effect is independent of glycoprotein IIb/IIIa activation and fibrinogen degradation, suggesting a unique mechanism for reperfusion therapy.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Hematology
Background:
- Clinical studies explore combining glycoprotein (GP) IIb/IIIa inhibitors with thrombolytic agents for acute myocardial infarction.
- Thrombolytic agents may possess intrinsic antiplatelet effects influencing reperfusion outcomes.
Purpose of the Study:
- To investigate the direct antiplatelet effects of tenecteplase, alteplase, and reteplase on blood samples from patients with coronary disease and healthy subjects.
- To determine if thrombolytic agents affect platelet aggregation, GP IIb/IIIa activation, P-selectin expression, and fibrinogen levels.
Main Methods:
- Blood samples were incubated with varying concentrations of tenecteplase, alteplase, or reteplase.
- Platelet aggregation induced by adenosine diphosphate (ADP) was measured.
- Stimulated expression of GP IIb/IIIa and P-selectin, and plasma fibrinogen levels were determined.
Main Results:
- Alteplase significantly inhibited platelet aggregation at medium and high concentrations, more so than tenecteplase or reteplase.
- Tenecteplase showed some inhibition of aggregation at high concentrations.
- No significant changes were observed in GP IIb/IIIa activation or P-selectin expression with any agent.
- Reteplase significantly decreased plasma fibrinogen levels at tested concentrations.
Conclusions:
- Alteplase exhibits potent antiplatelet activity, independent of GP IIb/IIIa activation and fibrinogen degradation.
- The antiplatelet effect of alteplase may be a crucial factor in its reperfusion efficacy.
- Findings support further research into combined therapies involving alteplase and antiplatelet agents.
Abstract:
Clinical studies have investigated the combination of glycoprotein (GP) IIb/IIIa inhibitors and thrombolytic agents for acute myocardial infarction. However, thrombolytic agents alone may possess direct antiplatelet properties that could affect reperfusion. Blood from 11 patients with coronary disease and five healthy subjects was incubated for 30 min with tenecteplase (4, 12, and 24 microg/ml), alteplase (1, 4, and 10 microg/ml), reteplase (1, 5, and 10 microg/ml) or control buffer. Platelet aggregation induced by 1, 20 and 50 micromol/l adenosine diphosphate (ADP), the stimulated expression of GP IIb/IIIa and P-selectin, and plasma fibrinogen levels were determined. Platelet aggregation in patients was inhibited by medium and high concentrations of alteplase when induced by 1 micromol/l ADP [1.6 +/- 0.5%, P = 0.001 and 0.9 +/- 0.2%, P = 0.002 versus 8.3 +/- 1.6% (control)] and 20 micromol/l ADP [46.9 +/- 3.9%, P = 0.001 and 46.2 +/- 4.8%, P = 0.001 versus 65.7 +/- 2.7% (control)]. High concentration tenecteplase was associated with lower aggregation by 20 micromol/l ADP (58 +/- 2.1% versus control, P = 0.033). There were no changes in GP IIb/IIIa activation or P-selectin expression in patients or healthy subjects. Platelet aggregation (1 micromol/l ADP) in healthy subjects was inhibited only by high doses of alteplase (P = 0.001). Plasma fibrinogen levels were significantly decreased after treatment with reteplase at 1 microg/ml(1.53 +/- 0.21 versus 2.65 +/- 0.31, P = .009) and 5 microg/ml(1.55 +/- 0.16 versus 2.65 +/- 0.31, P = .005). Alteplase inhibits platelet aggregation more than tenecteplase and reteplase. The attenuation of platelet aggregation by alteplase is dissociated from the expression of activated GP IIb/IIIa and P-selectin, and by fibrinogen degradation. These results suggest that alteplase exerts its antiplatelet effect independent of GP IIb/IIIa and P-selectin expressions and fibrinogen degradation. These findings may be directly relevant to the effect of alteplase on reperfusion and to future studies using combined platelet inhibitors and thrombolytic therapy.
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