Combination of Platelet expression of PKCepsilon and cardiac troponin-I for early diagnosis of chest pain patients in the emergency department

Cecilia Carubbi,Rosalia Aloe,Matteo Goldoni,Giulia Pozzi,Marco Vitale,Silvia Martini,Elena Masselli,Giuliana Gobbi,Maria Mattioli,Gianfranco Cervellin

doi:10.1038/s41598-019-38624-5

Cecilia Carubbi, Rosalia Aloe + Show 8 more

Open Access

https://doi.org/10.1038/s41598-019-38624-5

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Abstract

A rapid differential diagnosis of the clinical conditions underlying chest pain is a relevant clinical issue. Specifically, a fast rule-in or -out of acute myocardial infarction (AMI) is mandatory to improve diagnostic outcome and cost-effectiveness of patient management. We demonstrated that Protein Kinase C (PKC) epsilon is selectively expressed by platelets from AMI patients, accounting for increased platelet activation. Thus, we hypothesized that PKCepsilon-expressing platelets may represent a pathophysiological marker of AMI that could be utilized in combination with troponin-I, the conventional marker of cardiac injury, to add diagnostic information in chest pain workup. In 94 chest pain patients consecutively admitted to Parma University Hospital, we tested the diagnostic performance of flow-cytometric detection of PKCepsilon expressing platelets in discriminating AMI vs. non-AMI conditions. We demonstrated that PKCepsilon-expressing platelets were significantly higher in patients with AMI. Flow cytometry detection of PKCepsilon-expressing platelets showed high sensitivity and specificity (87.5% and 84.4%, respectively) and good diagnostic accuracy (AUC: 0.875). The combination of PKCepsilon expressing platelets and cardiac troponin clearly discriminates patients with 100% and 0% of probability to be affected by AMI. Overall, we highlighted a dual marker strategy potentially useful for a rapid rule-in or -out of myocardial infarction in chest pain patients.

Highlights

Chest pain (CP) is one of the leading complaints in patients seeking medical evaluation at emergency departments (EDs), accounting for up to 10% of the whole ED census[1,2]
We demonstrated that Flow cytometry (FCM) detection of platelet population expressing PKCe has a diagnostic feasibility, PKCe-expressing PLTs shows a high sensitivity and specificity (87.5% and 84.4%, respectively) and a good diagnostic accuracy (AUC: 0.875), that is similar to cardiac troponin (AUC: 0.843), the marker of choice for serological diagnosis of acute myocardial infarction (AMI)
We focused on platelets expressing PKCe, a disease-specific platelet protein, involved in the molecular pathways of platelet reactivity leading to platelet aggregation[27]

Summary

Introduction

Chest pain (CP) is one of the leading complaints in patients seeking medical evaluation at emergency departments (EDs), accounting for up to 10% of the whole ED census[1,2] It is a common symptom of both cardiac and non-cardiac disorders, and the underlying cause may vary from diseases with favorable prognosis to potentially life-threatening conditions, including myocardial infarction, pulmonary embolism, acute aortic syndromes, pneumothorax, or myocarditis. Laboratory tests – troponins included– should always be used in conjunction with all other information available to the clinicians[9,10,12,13,14] Given this scenario, new tools are eagerly needed to improve the diagnostic algorithm for CP patients and the cost- and time-effectiveness of ED management. We demonstrated that the ectopic expression of PKCe involves both mature and young platelets, excluding that the presence of PKCe-positive platelets could be selectively ascribed to newly formed platelets during AMI, rather suggesting that PKCe could be up-regulated before the acute event[21]

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