Inflammatory Mediators of Platelet Activation: Focus on Atherosclerosis and COVID-19

Background: Atherosclerotic cardiovascular diseases are characterized by a dysregulated inflammatory and thrombotic state, leading to devastating complications with increased morbidity and mortality rates. Summary: In this review article, we present the available evidence regarding the impact of inflammation on platelet activation in atherosclerosis. Key messages: In the context of a dysfunctional vascular endothelium, structural alterations by means of endothelial glycocalyx thinning or functional modifications through impaired NO bioavailability and increased levels of von Willebrand factor result in platelet activation. Moreover, neutrophil-derived mediators, as well as neutrophil extracellular traps formation, have been implicated in the process of platelet activation and platelet-leukocyte aggregation. The role of pro-inflammatory cytokines is also critical since their receptors are also situated in platelets while TNF-α has also been found to induce inflammatory, metabolic, and bone marrow changes. Additionally, important progress has been made towards novel concepts of the interaction between inflammation and platelet activation, such as the toll-like receptors, myeloperoxidase, and platelet factor-4. The accumulating evidence is especially important in the era of the coronavirus disease-19 pandemic, characterized by an excessive inflammatory burden leading to thrombotic complications, partially mediated by platelet activation. Lastly, recent advances in anti-inflammatory therapies point towards an anti-thrombotic effect secondary to diminished platelet activation.

Effect of Prolonged Hypothermic Cardiopulmonary Bypass, Heparin, and Protamine on Platelet: A Small-Group Study

Cardiopulmonary bypass (CPB) is associated with platelet dysfunction (PD), an important cause of postoperative bleeding. The etiology of PD is not completely understood. We mapped the platelets' function during CPB to determine the etiology of PD. Platelets activation, measured by procaspase activating compound-1 and P-selectin expression (CD62P), after activation by adenosine diphosphate and thrombin receptor activator peptide, were decreased by protamine. Changes during CPB were insignificant. Platelet-leukocyte aggregation was increased by CPB but not by protamine. Platelet apoptosis marker, annexin V, was increased by protamine. Changes during CPB were insignificant. Our findings demonstrate that protamine given after CPB plays a central role in PD and count decrease.

The Role of CD147 in Leukocyte Aggregation in Liver Injury

BackgroundChronic inflammation is the driver of liver injury resulting in progressive fibrosis and eventual cirrhosis. The consequences include both liver failure and liver cancer. We have previously described increased expression of the highly multifunctional glycoprotein CD147 in liver injury. This work describes a novel role of CD147 in liver inflammation and the importance of leukocyte aggregates in determining the extent of liver injury.MethodsNon-diseased, progressive injury and cirrhotic liver from humans and mice were examined using mAb targeting CD147. Inflammatory cell subsets were assessed by multicolor flow cytometry.ResultsIn liver injury, we observe abundant intrahepatic leukocyte clusters defined as ≥5 adjacent CD45+cells which we have labelled “leukocyte aggregates”. We have shown that these leukocyte aggregates are significant in determining the extent of liver injury. If CD147 is blockedin vivo,these leukocyte aggregates diminish in size and number together with a marked significant reduction in liver injury including fibrosis. This accompanied by no change in overall intrahepatic leukocyte numbers. Further, blocking aggregation formation occurs prior to an appreciable increase in inflammatory markers or fibrosis. Additionally, there were no observed, “off-target” or unpredicted effects in targeting CD147.ConclusionCD147 mediates leukocyte aggregation which is associated with the development of liver injury. This is not a secondary effect, but a cause of injury as aggregate formation proceeds other markers of injury. Leukocyte aggregation has been previously described in inflammation dating back over many decades but till now been shown to determine the extent of injury.

Correlation between leukocyte aggregation score of cerebrospinal fluid and bacterial meningitis in children

Background Bacterial meningitis is one of life-threatening dis-eases and carries a risk of sequelae in affected children. In termsof cost and rapid differentiation between bacterial and non-bacte-rial meningitis, several tests have been proposed.Objective This study aimed to determine the use of leukocyteaggregation score (LAS) of cerebrospinal fluid (CSF) in diagnos-ing bacterial meningitis.Methods A prospective analytic study was done from October 2001to July 2002 in the Department of Child Health, Medical School,Sam Ratulangi University/ Manado General Hospital. Children pre-senting with symptoms of meningitis, aged between 28 days and13 years were enrolled. LAS was counted in percentage. Regres-sion analysis was used to determine the correlation between LASand diagnosis of bacterial meningitis.Results CSF examinations were done on 35 meningitis patients.Three patients were excluded. The remaining 32 patients com-prised of 11 with bacterial meningitis and the other 21 with non-bacterial meningitis. The mean of LAS in bacterial meningitis wassignificantly higher than that of non-bacterial meningitis (p<0.001).The cut off value of LAS to diagnose bacterial meningitis was12.35%.Conclusion LAS may be used as a fast and simple alternativediagnostic tool to confirm the diagnosis of bacterial meningitis