Enhanced Response to Chemotactic Activation of Polymorphonuclear Leukocytes from Patients with Heart Valve Replacement

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.