Antiplatelet Agents Have a Distinct Efficacy on Platelet Aggregation Induced by Infectious Bacteria

Abstract

Platelets are the cornerstone of hemostasis. However, their exaggerated aggregation induces deleterious consequences. In several diseases, such as infectious endocarditis and sepsis, the interaction between platelets and bacteria leads to platelet aggregation. Despite platelet involvement, no antiplatelet therapy is currently recommended in these infectious diseases. We aimed here, to evaluate, in vitro, the effect of antiplatelet drugs on platelet aggregation induced by two of the bacterial pathogens most involved in infectious endocarditis, Staphylococcus aureus and Streptococcus sanguinis. Blood samples were collected from healthy donors (n = 43). Treated platelet rich plasmas were incubated with three bacterial strains of each species tested. Platelet aggregation was evaluated by Light Transmission Aggregometry. CD62P surface exposure was evaluated by flow cytometry. Aggregate organizations were analyzed by scanning electron microscopy. All the strains tested induced a strong platelet aggregation. Antiplatelet drugs showed distinct effects depending on the bacterial species involved with different magnitude between strains of the same species. Ticagrelor exhibited the highest inhibitory effect on platelet activation (p <0.001) and aggregation (p <0.01) induced by S. aureus. In the case of S. sanguinis, platelet activation and aggregation were better inhibited using the combination of both aspirin and ticagrelor (p <0.05 and p <0.001 respectively). Aggregates ultrastructure and effect of antiplatelet drugs observed by scanning electron microscopy depended on the species involved. Our results highlighted that the effect of antiplatelet drugs depended on the bacterial species involved. We might recommend therefore to consider the germ involved before introduction of an optimal antiplatelet therapy.

Characterization of a bacterial strain Lactobacillus paracasei LP10266 recovered from an endocarditis patient in Shandong, China

“…The neutrophil phagocytic assay showed that the difference of the neutrophil phagocytic rate of L. paracasei LP10266 and L. paracasei ATCC25302 was statistically significant ( p = 0.044). Platelet aggregation caused by bacteria is an important source of infective endocarditis [ 31 ]. Many Gram-positive bacteria causing sepsis have been shown to induce platelet aggregation [ 32 ].…”

Aspirin or Ticagrelor in Staphylococcus aureus Infective Endocarditis: Where Do We Stand?

“…Heying et al (2019) proposed that the bactericidal properties of ticagrelor could resemble the aspirin effect, modulating the expression of S. aureus virulence factors with a decrease in the expression of MSCRAMM's and toxins. The potential inhibitory effect of ticagrelor on bacteria-platelet interactions was further supported by an in vitro study reporting the highest inhibitory effect of bacteria-induced platelet aggregation by ticagrelor as compared to aspirin, aspirin plus ticagrelor, or tirofiban (Hannachi et al, 2020). Very recently, two studies described an inhibitory effect of ticagrelor on α-toxin mediated platelet clearance by the hepatic AMR pathways, thereby preserving the antibacterial activity of platelets (Sun et al, 2021;Ulloa et al, 2021).…”

“…The initial phase of IE development involves the interplay between platelets and bacteria (Figure 1; Hamzeh-Cognasse et al, 2015;Liesenborghs et al, 2018Liesenborghs et al, , 2019, which strongly suggests an essential role for platelets in early stages of IE. Vegetations could form either via indirect or direct interaction of bacteria with platelets (Hamzeh-Cognasse et al, 2015;Hannachi et al, 2020; Figure 1). S. aureus -bacteria interactions are mainly mediated through binding of the GPIIb/IIIa platelet receptor (integrin a IIb b 3 ) (Hamzeh-Cognasse et al, 2015;Liesenborghs et al, 2018Liesenborghs et al, , 2020.…”

Association of Staphylococcus aureus in platelet concentrates with skin diseases in blood donors: Limitations of cultural bacterial screening

“…Previous studies have shown that S. aureus produces fibrinogen‐binding protein, and the membrane surface protein binds to platelet receptors to cause platelet aggregation in platelet‐rich plasma at higher bacterial levels 29 . At that time, bacterial cells accumulate in the aggregates 30 . These mechanisms may reduce the bacterial concentration (even to zero) in the liquid phase of plasma by culture.…”

“…29 At that time, bacterial cells accumulate in the aggregates. 30 These mechanisms may reduce the bacterial concentration (even to zero) in the liquid phase of plasma by culture. In S. aureus-contaminated PC units, some aggregations are often found using visual inspection after day 3 and thereafter and can, thus, be excluded before transfusion.…”