Platelet Biomarkers in Patients with Atherosclerotic Extracranial Carotid Artery Stenosis: A Systematic Review
Arun Subramanian1, Siobhan Delaney1, Stephen J X Murphy1
1Department of Neurology, Tallaght University Hospital/Adelaide and Meath Hospital, Dublin, Incorporating the National Children's Hospital (AMNCH), Tallaght, Dublin, Ireland; Stroke Service, Tallaght University Hospital/Adelaide and Meath Hospital, Dublin, Incorporating the National Children's Hospital (AMNCH), Tallaght, Dublin, Ireland.
Insights
Platelets show increased activation in carotid stenosis patients, especially those with symptoms. Current tests for platelet reactivity are not recommended for guiding therapy outside research settings.
Area of Science:
- Cardiovascular Research
- Hematology
- Neuroscience
Background:
- Atherosclerotic carotid stenosis poses a significant risk for vascular events.
- Platelet activation plays a crucial role in the pathogenesis of atherosclerosis and thrombosis.
- Understanding platelet behavior is key for risk stratification and therapeutic strategies.
Purpose of the Study:
- To review the role of platelet biomarkers in vascular events related to carotid stenosis.
- To assess the utility of platelet function tests in risk stratifying patients with carotid stenosis.
- To understand platelet activation in asymptomatic and symptomatic carotid stenosis.
Main Methods:
- Systematic review of studies from 1975 to 2020.
- Inclusion of studies on ex vivo platelet activation and function in carotid stenosis.
- Adherence to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
Main Results:
- Increased platelet biomarkers were observed in patients with asymptomatic carotid stenosis (ACS) (≥30%).
- Platelet activation was excessive in symptomatic carotid stenosis (SCS) patients (≥30%).
- High on-treatment platelet reactivity (HTPR) was common, but ex vivo testing is not yet recommended for therapy adjustment.
Conclusions:
- Platelets are hyper-activated in carotid stenosis, particularly in symptomatic patients, even on antiplatelet therapy.
- Platelet activation may increase post-intervention (endarterectomy, stenting).
- Further research is needed to integrate platelet biomarkers with clinical and imaging data for personalized antiplatelet therapy.
Objective:
The aim was to enhance understanding of the role of platelet biomarkers in the pathogenesis of vascular events and risk stratifying patients with asymptomatic or symptomatic atherosclerotic carotid stenosis.
Data Sources:
Systematic review conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.
Review Methods:
A systematic review collated data from 1975 to 2020 on ex vivo platelet activation and platelet function/reactivity in patients with atherosclerotic carotid stenosis.
Results:
Forty-three studies met the inclusion criteria; the majority included patients on antiplatelet therapy. Five studies showed increased platelet biomarkers in patients with ≥ 30% asymptomatic carotid stenosis (ACS) vs. controls, with one neutral study. Preliminary data from one study suggested that quantification of "coated platelets" in combination with stenosis severity may aid risk stratification in patients with ≥ 50% - 99% ACS. Platelets were excessively activated in patients with ≥ 30% symptomatic carotid stenosis (SCS) vs. controls (≥ 11 positive studies and one neutral study). Antiplatelet-High on Treatment Platelet Reactivity (HTPR), previously called "antiplatelet resistance", was observed in 23% - 57% of patients on aspirin, with clopidogrel-HTPR in 25% - 100% of patients with ≥ 50% - 99% ACS. Aspirin-HTPR was noted in 9.5% - 64% and clopidogrel-HTPR in 0 - 83% of patients with ≥ 50% SCS. However, the data do not currently support the use of ex vivo platelet function/reactivity testing to tailor antiplatelet therapy outside of a research setting. Platelets are excessively activated (n = 5), with increased platelet counts (n = 3) in recently symptomatic vs. asymptomatic patients, including those without micro-emboli on transcranial Doppler (TCD) monitoring (n = 2). Most available studies (n = 7) showed that platelets become more reactive or activated following carotid endarterectomy or stenting, either as an acute phase response to intervention or peri-procedural treatment.
Conclusion:
Platelets are excessively activated in patients with carotid stenosis vs. controls, in recently symptomatic vs. asymptomatic patients, and may become activated/hyper-reactive following carotid interventions despite commonly prescribed antiplatelet regimens. Further prospective multicentre studies are required to determine whether models combining clinical, neurovascular imaging, and platelet biomarker data can facilitate optimised antiplatelet therapy in individual patients with carotid stenosis.
Related Concept Videos
01:19Blood Studies for Cardiovascular System II: CRP, Hcy, and Cardiac Natriuretic Peptide Markers
These markers indicate stress or strain on the heart muscle:
Natriuretic Peptides (BNP)
Cardiac myocytes produce these hormones in response to ventricular stretching...
01:20Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
01:27Atherosclerosis II: Clinical Manifestations and Diagnostic Tests
01:25Imaging Studies for Cardiovascular System VI: Calcium -Scoring CT
01:20Blood Studies for Cardiovascular System I: Cardiac Biomarkers
The essential diagnostic tools for detecting myocardial necrosis and monitoring individuals suspected of having acute coronary syndrome (ACS) include:
Troponins
Troponins, particularly cardiac troponins I and T, are the most precise and sensitive markers of myocardial injury. They are detectable within 4-6 hours of myocardial injury and remain...