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Enhanced response to chemotactic activation of polymorphonuclear leukocytes from patients with heart valve
N Maugeri1, A C Kempfer, V Evangelista
1Department of Thrombosis and Hemostasis, National Academy of Medicine, Buenos Aires, Argentina.
Abstract:
Artificial surfaces activate blood components. Since anticoagulant and antiplatelet therapy fail to abolish thromboembolic complications in patients with mechanical heart valve replacement (MHVR), other mechanisms might contribute to switch on a thrombotic event. We therefore investigated the reactivity to chemotactic activation of PMN from patients with MHVR. PMN responses were analyzed in 3 groups: 130 patients with MHVR and oral anticoagulant therapy, with or without aspirin, 57 patients on a comparable antithrombotic regimen, but without MHVR and 50 healthy subjects. In vitro studies showed that the release of cathepsin G and elastase from fMLP-stimulated PMN was significantly higher in the MHVR group, the leukocyte content of alpha 1-antitrypsin (an inhibitor of both enzymes) being similar in all three groups. CD11b expression after stimulation with fMLP was also significantly higher on PMN from MHVR patients than from control patients or healthy volunteers, while PMN CD11b basal expression was similar in all three groups. This increased PMN response in vitro in the absence of an obvious activation in vivo, may reflect a modified reactivity of circulating PMN passing through the artificial valves. Increased reactivity to local stimuli might allow PMN to participate in thrombus formation, despite conventional antithrombotic therapy.
Insights
Patients with mechanical heart valve replacement show increased polymorphonuclear neutrophil (PMN) reactivity. This heightened response may contribute to thrombotic events despite anticoagulant therapy.
Area of Science:
- Biomedical Engineering
- Hematology
- Cardiovascular Research
Background:
- Artificial surfaces, like mechanical heart valves, can activate blood components.
- Standard anticoagulant and antiplatelet therapies are insufficient to prevent thromboembolic complications in mechanical heart valve replacement (MHVR) patients.
Purpose of the Study:
- To investigate the reactivity of polymorphonuclear neutrophils (PMN) to chemotactic activation in patients with MHVR.
- To explore alternative mechanisms contributing to thrombotic events in MHVR patients.
Main Methods:
- Analyzed PMN responses in three groups: MHVR patients (with/without aspirin), non-MHVR patients on antithrombotics, and healthy controls.
- Utilized in vitro studies to measure cathepsin G and elastase release from fMLP-stimulated PMN.
- Assessed CD11b expression on PMN following fMLP stimulation.
Main Results:
- PMN release of cathepsin G and elastase was significantly higher in MHVR patients compared to controls.
- CD11b expression on stimulated PMN was significantly elevated in MHVR patients.
- Leukocyte alpha 1-antitrypsin levels were similar across all groups, indicating no compensatory inhibition.
Conclusions:
- MHVR patients exhibit increased PMN reactivity in vitro, potentially due to altered PMN behavior after passing through artificial valves.
- This enhanced PMN responsiveness may play a role in thrombus formation, even with conventional antithrombotic treatments.
- Further research is needed to understand the implications of this altered PMN function in MHVR patients.