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Antithrombotic effects of abciximab
R Hayes1, J H Chesebro, V Fuster
1Zena and Michael A. Wiener Cardiovascular Institute, New York, New York 10029, USA.
Abstract:
The observation that platelet-platelet interaction and thrombosis are ultimately regulated by the glycoprotein (GP) IIb/IIIa receptor complex, triggered the development of agents capable of interfering with this platelet receptor complex. Several large clinical trials have demonstrated the effectiveness of this class of agents. The first of these agents to show beneficial effects after coronary interventions was the mouse/human chimeric Fab fragment antibody c7E3 (abciximab; ReoPro). This study analyzes whether the addition of heparin to the GP IIb/IIIa antagonist abciximab would enhance the antithrombotic effect. Blood drawn directly from patients on aspirin who underwent interventional procedures perfused an ex vivo perfusion chamber containing a severely injured arterial wall at local rheologic conditions of a mildly stenosed coronary artery. Blood was perfused directly from patients at baseline and following administration of heparin, abciximab, or both. The antithrombotic effects of the 3 treatments were assessed by reduction of the thrombus formation on the perfused specimens. Thrombus formation at baseline was not significantly modified by the administration of heparin (13,897 +/- 1,316 vs 11,917 +/- 1,519 microm(2)). Abciximab produced a 58% reduction in thrombus formation (11,631 +/- 861 vs 4, 925 +/- 585 microm(2); p <0.001). The addition of heparin to abciximab did not further reduce thrombus area versus abciximab alone (5,651 +/- 581 vs 4,925 +/- 585 microm(2)). Thus, our data show that abciximab dramatically decreases mural thrombus formation and that combining heparin with abciximab did not add any additional antithrombotic effect to abciximab alone.
Insights
Adding heparin to abciximab, a glycoprotein IIb/IIIa antagonist, did not enhance its antithrombotic effect in patients undergoing interventions. Abciximab alone significantly reduced thrombus formation, with no added benefit from heparin.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Pharmacology
Background:
- Platelet aggregation and thrombosis are regulated by the glycoprotein (GP) IIb/IIIa receptor complex.
- GP IIb/IIIa antagonists, like abciximab, interfere with this receptor complex and have shown effectiveness in clinical trials.
- Abciximab (c7E3 Fab fragment) was the first agent in this class to demonstrate benefits after coronary interventions.
Purpose of the Study:
- To investigate whether combining heparin with the GP IIb/IIIa antagonist abciximab enhances antithrombotic effects.
- To assess the additive antithrombotic potential of heparin when used alongside abciximab in patients on aspirin undergoing interventional procedures.
Main Methods:
- An ex vivo perfusion chamber model was used with blood from patients on aspirin undergoing interventional procedures.
- Blood was perfused over a severely injured arterial wall under conditions mimicking a mildly stenosed coronary artery.
- Treatments assessed included baseline, heparin alone, abciximab alone, and the combination of abciximab and heparin, with thrombus formation quantified.
Main Results:
- Heparin alone did not significantly alter baseline thrombus formation.
- Abciximab demonstrated a significant 58% reduction in thrombus formation compared to baseline (p <0.001).
- The addition of heparin to abciximab did not result in a further reduction in thrombus area compared to abciximab alone.
Conclusions:
- Abciximab effectively and significantly decreases mural thrombus formation.
- Combining heparin with abciximab does not provide additional antithrombotic benefits beyond abciximab monotherapy in this setting.
- These findings suggest that abciximab alone is sufficient for substantial antithrombotic effect in patients on aspirin undergoing interventions.