Platelets and Their Role in the Pathogenesis of Cardiovascular Events in Patients With Community-Acquired Pneumonia

Abstract

Community-acquired pneumonia (CAP) remains an important cause of morbidity and mortality throughout the world with much recent and ongoing research focused on the occurrence of cardiovascular events (CVEs) during the infection, which are associated with adverse short-term and long-term survival. Much of the research directed at unraveling the pathogenesis of these events has been undertaken in the settings of experimental and clinical CAP caused by the dangerous, bacterial respiratory pathogen, Streptococcus pneumoniae (pneumococcus), which remains the most common bacterial cause of CAP. Studies of this type have revealed that although platelets play an important role in host defense against infection, there is also increasing recognition that hyperactivation of these cells contributes to a pro-inflammatory, prothrombotic systemic milieu that contributes to the etiology of CVEs. In the case of the pneumococcus, platelet-driven myocardial damage and dysfunction is exacerbated by the direct cardiotoxic actions of pneumolysin, a major pore-forming toxin of this pathogen, which also acts as potent activator of platelets. This review is focused on the role of platelets in host defense against infection, including pneumococcal infection in particular, and reviews the current literature describing the potential mechanisms by which platelet activation contributes to cardiovascular complications in CAP. This is preceded by an evaluation of the burden of pneumococcal infection in CAP, the clinical features and putative pathogenic mechanisms of the CVE, and concludes with an evaluation of the potential utility of the anti-platelet activity of macrolides and various adjunctive therapies.

Acetylsalicylic acid use is associated with improved survival in bacteremic pneumococcal pneumonia: A long‐term nationwide study

“…Cardiovascular complications in the setting of pneumonia are thought to be caused by a combination of factors, including hypoxemia, damage to the myocardium, inflammatory response, plaque destabilization, platelet activation, and diminished perfusion of coronary arteries [10,13,20,40,41]. Finally, pneumococcal antigen persistence can result in a chronic inflammatory response, which could also play a role [42,43].…”

Administration of recombinant human thrombopoietin is associated with alleviated thrombocytopenia in adult intensive care unit patients with pneumonia: A single-center retrospective study

“…The lung is also a primary site for platelet biogenesis and reservoirs ( Lefrançais and Looney, 2019 ), which are responsible for approximately 50% of total platelet production ( Lefrançais et al, 2017 ). Platelets also contribute to the pathophysiology of a variety of lung disorders and to systemic syndromes that involve the lungs ( Weyrich and Zimmerman 2013 ); they have been found to trap, sequester and, in some cases, eliminate invasive pathogens in pneumonia such as pneumococcus, Haemophilus influenzae, Staphylococcus aureus, and viruses ( Feldman and Anderson 2020 ). Thus, platelets play a significant role in restraining bacterial infections to the lung ( Amison et al, 2018 ).…”

Risk of cardiovascular events leading to hospitalisation afterStreptococcus pneumoniaeinfection: a retrospective cohort LIFE Study

“…28 Many studies that seek to understand the pathogenesis of cardiovascular events following pneumonia focus on infections caused by S. pneumoniae. 29 Several studies have proposed that S. pneumoniae cell wall components and pneumolysin (a poreforming toxin) trigger proinflammatory mechanisms that ultimately result in cardiac damage. [30][31][32][33] Furthermore, the infection-mediated hyperactivation of platelets can create a proinflammatory and prothrombotic environment that facilitates the occurrence of cardiovascular events and cardiac damage.…”

“…S. pneumoniae reportedly reduces cardiac contractility by increasing cardiomyocyte uptake of bacterial cell wall antigens 28. Many studies that seek to understand the pathogenesis of cardiovascular events following pneumonia focus on infections caused by S. pneumoniae 29. Several studies have proposed that S. pneumoniae cell wall components and pneumolysin (a pore-forming toxin) trigger proinflammatory mechanisms that ultimately result in cardiac damage 30–33.…”