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

Bartosz Ditkowski; Martyna Bezulska-Ditkowska; Ramadan Jashari; Pieter Baatsen; Philippe Moreillon; Filip Rega; Tiago R Veloso; Marc F Hoylaerts; Ruth Heying; Congenital Cardiology and Cardiac Surgery Group

doi:10.1016/j.jtcvs.2019.10.188

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

J Thorac Cardiovasc Surg. 2021 Jun;161(6):e457-e472. doi: 10.1016/j.jtcvs.2019.10.188. Epub 2019 Nov 23.

Authors

Bartosz Ditkowski¹, Martyna Bezulska-Ditkowska², Ramadan Jashari³, Pieter Baatsen⁴, Philippe Moreillon⁵, Filip Rega⁶, Tiago R Veloso¹, Marc F Hoylaerts⁷, Ruth Heying⁸; Congenital Cardiology and Cardiac Surgery Group

Collaborators

Congenital Cardiology and Cardiac Surgery Group:
Marc Gewillig⁹, Bart Meyns⁹

Affiliations

¹ Cardiovascular Developmental Biology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.
² Cardiovascular Developmental Biology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium; Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.
³ European Homograft Bank, Saint Jean Clinique, Brussels, Belgium.
⁴ Department of Neurosciences, VIB-KU Leuven Center for Brain & Disease Research, KU Leuven and EM-platform of VIB Bio Imaging Core @KULeuven, Leuven, Belgium.
⁵ Department of Fundamental Microbiology, University Lausanne, Lausanne, Switzerland.
⁶ Division of Clinical Cardiac Surgery, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.
⁷ Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.
⁸ Cardiovascular Developmental Biology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium. Electronic address: ruth.heying@uzleuven.be.
⁹ Department of Cardiovascular Sciences, Cardiovascular Developmental Biology, KU Leuven, Leuven, Belgium; Division of Clinical Cardiac Surgery, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.

PMID: 31926702
DOI: 10.1016/j.jtcvs.2019.10.188

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: S aureus; cardiac graft tissues; fibrinogen; infective endocarditis; platelets.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bacterial Adhesion
Bioprosthesis*
Blood Platelets / physiology
Cattle
Endocarditis, Bacterial*
Fibrinogen
Heart Valves* / microbiology
Heart Valves* / physiopathology
Platelet Aggregation Inhibitors*
Protein Binding
Staphylococcal Infections*
Staphylococcus aureus

Substances

Platelet Aggregation Inhibitors
Fibrinogen