Antiplatelet therapy abrogates platelet-assisted Staphylococcus aureus infectivity of biological heart valve conduits

Although recent advances in pulmonary valve replacement have enabled excellent hemodynamics, infective endocarditis remains a serious complication, particularly for implanted bovine jugular vein (BJV) conduits.

We investigated contributions by platelets and plasma fibrinogen to endocarditis initiation on various grafts used for valve replacement. Thus, adherence of Staphylococcus aureus and platelets to 5 graft tissues was studied quantitatively in perfusion chambers, assisted by microscopic analysis. We also evaluated standard antiplatelet therapy to prevent onset of S aureus endocarditis.

Of all tissues, bovine pericardium (BP) showed the greatest fibrinogen binding. Perfusion of all plasma-precoated tissues identified BP and BJV_wall with the greatest affinity for S aureus. Perfusions of anticoagulated human blood over all tissues also triggered more platelet adhesion to BP and BJV_wall as single platelets. Several controls confirmed that both S aureus and platelets were recruited on immobilized fibrinogen. In addition, perfusions (and controls) over plasma-coated tissues with whole blood, spiked with S aureus, revealed that bacteria exclusively bound to adhered platelets. Both the platelet adhesion and platelet-mediated S aureus recruitment required platelet α_IIbβ₃ and coated or soluble fibrinogen, respectively, interactions abrogated by the α_IIbβ₃-antagonist eptifibatide. Also, standard antiplatelet therapy (aspirin/ticagrelor) reduced the adherence of S aureus in blood to BJV 3-fold.

Binding of plasma fibrinogen to especially BJV grafts enables adhesion of single platelets via α_IIbβ₃. S aureus then attaches from blood to (activated) bound platelet α_IIbβ₃ via plasma fibrinogen. Dual antiplatelet therapy appears a realistic approach to prevent endocarditis and its associated mortality.