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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.

SUBMITTER: Hannachi N

PROVIDER: S-EPMC7291881 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Hannachi Nadji N Ogé-Ganaye Emma E Baudoin Jean-Pierre JP Fontanini Anthony A Bernot Denis D Habib Gilbert G Camoin-Jau Laurence L

Frontiers in pharmacology 20200605

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, <i>in vitro</i>, the effect of antiplatelet drugs on platelet aggregation induced by two of the bacter ...[more]

PMID: 32581813

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Project description:AimThe aim of this study was to evaluate the in vitro effect of coumarin and 15 monosubstituted derivatives on the inhibition of human platelet aggregation induced by various proaggregatory agonists, particularly by epinephrine.BackgroundThe emergence of residual platelet reactivity during the use of conventional antiplatelet agents (acetylsalicylic acid and clopidogrel) is one of the main causes of double therapy´s therapeutic failure. Platelet adrenoceptors participate in residual platelet reactivity. Therefore, it is necessary to develop new antiplatelet agents that inhibit epinephrine-induced platelet aggregation as a new therapeutic strategy. Information on the antiplatelet activity of coumarins in inhibiting epinephrine-induced aggregation is limited.ObjectiveThe objective of this study was to establish the structure-activity relationship (SAR) of coumarin derivatives with hydroxy, methoxy, and acetoxy groups in different positions of the coumarin nucleus to identify the most active molecules. Moreover, this study aimed to use in silico studies to suggest potential drug targets to which the molecules bind to produce antiplatelet effects.MethodsThe platelet aggregation was performed using a Lumi-aggregometer; the inhibitory activity of 16 compounds were evaluated by inducing the aggregation of human platelets (250 × 103/μl) with epinephrine (10 μM), collagen (2 μg/ml) or ADP (10 μM). The aggregation of control platelets was considered 100% of the response for each pro-aggregatory agonist.ResultsEleven molecules inhibited epinephrine-induced aggregation, with 3-acetoxycoumarin and 7-methoxycoumarin being the most active. Only coumarin inhibited collagen-induced platelet aggregation, but no molecule showed activity when using ADP as an inducer.ConclusionsIn silico studies suggest that most active molecules might have antagonistic interactions in the α2 and β2 adrenoceptors. The antiplatelet actions of these coumarins have the potential to reduce residual platelet reactivity and thus contribute to the development of future treatments for patients who do not respond adequately to conventional agents.

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

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

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