Platelet indices as diagnostic and prognostic markers in acute coronary syndrome

Gokul Krishnan; M Mukhyaprana Prabhu; Weena Stanley

doi:10.12688/f1000research.152404.1

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Research Article

Platelet indices as diagnostic and prognostic markers in acute coronary syndrome

[version 1; peer review: awaiting peer review]

Gokul Krishnan¹, M Mukhyaprana Prabhu ¹, Weena Stanley¹

PUBLISHED 15 Aug 2024

Author details Author details

¹ Department of Medicine, Manipal, Manipal Academy of Higher Education, Kasturba Medical College Manipal, Manipal, Karnataka, India

Gokul Krishnan
Roles: Conceptualization, Investigation, Methodology, Writing – Original Draft Preparation

M Mukhyaprana Prabhu
Roles: Conceptualization, Methodology, Writing – Review & Editing

Weena Stanley
Roles: Methodology, Supervision, Writing – Review & Editing

OPEN PEER REVIEW

REVIEWER STATUS AWAITING PEER REVIEW

This article is included in the Manipal Academy of Higher Education gateway.

Abstract

Background

Acute coronary syndromes refer to STEMI, NSTEMI and unstable angina.

The preferred biomarkers for assessing myocardial damage are cTnI and cTnT, and high-sensitivity cardiac troponin assays are recommended in clinical practice. Other biomarkers such as CK-MB have lower sensitivity and specificity.

Platelets play a major role in thrombosis, which is a causative factor for most acute coronary syndromes. In our study, we attempted to analyze the effectiveness of platelet indices (mean platelet volume, platelet count, and platelet distribution width) as diagnostic and prognostic markers in acute coronary syndromes.

Our data suggest that mean platelet volume and platelet distribution width are potential diagnostic markers, and plateletcrits can serve as prognostic markers.

Methods

A total of 290 subjects were recruited for the study, including 145 cases and 145 controls matched for sex and age. Cases presented with the first episode of acute coronary syndrome. Controls are those without acute coronary syndrome during present admission or in the past.

Results

MPV and plateletcrit correlated with both troponin T and pro-BNP, whereas PDW showed a positive correlation only with troponin T. The only significant correlation was between the plateletcrit and pro-BNP levels. The plateletcrit showed a positive correlation with other parameters (degree of ventricular dysfunction, severity of coronary artery disease, and presence of arrhythmia). On comparing platelet indices with risk factors for coronary artery disease, such as diabetes mellitus and dyslipidemia, MPV showed a positive correlation with HbA1c and the entire lipid profile, whereas PDW showed a positive correlation only with HbA1c and triglycerides. The plateletcrit was positively correlated with HbA1c and total cholesterol levels.

Conclusions

Our data suggest that mean platelet volume and platelet distribution width are potential diagnostic markers, whereas plateletcrits can serve as prognostic markers.

Keywords

Platelet indices, Acute coronary syndromes, MPV, PCT, PDW

Corresponding author: M Mukhyaprana Prabhu

Competing interests: No competing interests were disclosed.

Grant information: The author(s) declared that no grants were involved in supporting this work.

Copyright: © 2024 Krishnan G et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Krishnan G, Prabhu MM and Stanley W. Platelet indices as diagnostic and prognostic markers in acute coronary syndrome [version 1; peer review: awaiting peer review]. F1000Research 2024, 13:927 (https://doi.org/10.12688/f1000research.152404.1) First published: 15 Aug 2024, 13:927 (https://doi.org/10.12688/f1000research.152404.1) Latest published: 15 Aug 2024, 13:927 (https://doi.org/10.12688/f1000research.152404.1)

Introduction

Acute coronary syndrome (ACS) is a major cause of mortality worldwide. There are several protocols for the diagnosis and triaging of ACS, including ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), and unstable angina, all aimed at timely diagnosis and early referral if indicated, which is essential for a favorable outcome.¹

The preferred biomarkers for assessing myocardial damage in ACS are cardiac troponin T (cTnT) and cardiac troponin I (cTnI). It is recommended that high-sensitivity cardiac troponin assays should be used in clinical practice.²^–⁵ Other biomarkers such as CK-MB have lower sensitivity and specificity.⁶ Platelets play a major role in thrombosis, which is a causative factor for most acute coronary syndromes.

Enzyme markers with good specificity have a few disadvantages, such as being negative during the window period and may not be available at all centers.⁷ Therefore in our study, we attempted to determine how effective platelet indices (mean platelet volume, platelet count, and platelet distribution width) are diagnostic markers in acute coronary syndromes. Additionally, we attempted to assess their prognostic ability among cases of ACS.

Methods

Study design

This prospective case-control study was conducted at Kasturba Hospital, Manipal, India, from May 2020 to September 2021.

Setting

The study was approved by our Institutional Review Board (IRB) known as Kasturba Medical College and Kasturba Hospital Institutional Ethics Committee (reference number: 954/2019) on 19th November, 2019. This study was conducted in accordance with the principles of the Declaration of Helsinki. Written informed consent was obtained from all the participants.

Participants and sample size

The total sample size was 290, with cases and controls in a ratio of 1:1. All the cases meeting the inclusion criteria over the mentioned study period were included. Blood was collected from cases and controls in ethylenediaminetetraacetic acid (EDTA) tubes, and samples were analyzed using automated analyzers: Beckman Coulter DxH™ 800, Beckman Coulter DxH™ 900 and Sysmex XN1500 ™.

Inclusion criteria for cases

- Those presenting with the first episode of acute coronary syndrome (ACS)

Inclusion criteria for controls

- Those without acute coronary syndrome at present or in the past

Exclusion criteria for cases and controls

- Those on antiplatelet agents
- Those with abnormalities in platelet count (thrombocytopenia/thrombocytosis)

Variables

Diagnosis of acute coronary syndrome among cases was made according to the fourth universal definition of myocardial infarction.⁸ Those with unstable angina, non ST elevation myocardial infarction and ST elevation myocardial infarction were considered. Platelet indices (MPV, PCT and PDW) at admission were noted among both the groups. Among cases, in addition to platelet indices, other parameters like troponin T levels, pro BNP levels echocardiography findings, and coronary angiography results were also recorded with intend to analyse their ability to serve as potential prognostic markers.

Data sources & bias

Cases as mentioned above were cases of acute coronary syndrome. Controls were patients who presented to our center but without a diagnosis of ACS. Cases and controls were matched for age and gender.

Statistical analysis

Statistical analysis was done using SPSS version 21.0.⁸ Continuous and normally distributed variables were expressed as mean ± standard deviation, and general characteristics were compared using the chi-square test and t-test. Statistical significance was set of statistical significance.

Results

A total of 145 patients and 145 controls were included in this study [Table 1]. Among the cases, the majority had STEMI, followed by NSTEMI, and unstable angina [Table 2]. On comparing platelet indices between cases and controls, all of them (MPV, plateletcrit, and PDW) were found to be higher among the cases. However, only the MPV was statistically significant [Table 3].

Table 1. Demographics.

Age	Cases	Controls
30 and below	2.1%(3)	4.1%(6)
31-40	2.1%(3)	2.1%(3)
41-50	15.2%(23)	14.5%(21)
51-60	34.5%(49)	33.8 %(49)
61-70	35.2%(51)	35.9%(52)
≥70	11%(16)	9.7%(14)
Gender
Male	110	110
Female	35	35

Table 2. Acute coronary syndrome subtypes among cases.

ACS subtypes	Frequency (percentage)
STEMI	80(55.2%)
NSTEMI	52(35.9%)
Unstable angina	13(9%)

Table 3. Platelet indices among cases and controls.

Platelet indices	Case (mean, standard deviation)	Control (mean, standard deviation)	P value (t test)
MPV (fL)	8.38 ± 0.96	8.03 ± 0.90	0.006
Plateletcrit (%)	0.2198 ± 0.0647	0.2158 ± 0.0588	0.585
PDW (%)	16.65 ± 0.97	16.60 ± 0.60	0.160

When platelet indices were compared to the laboratory markers, Troponin T, pro-BNP, MPV, and plateletcrit correlated with both troponin T and pro-BNP, while PDW showed a positive correlation only with troponin T. The only significant correlations were between plateletcrits and pro-BNP [Table 4]. The degree of ventricular dysfunction, severity of coronary artery disease, and existence or absence of arrhythmias were among the other criteria whose relation with the platelet indices were studied. Plateletcrit showed a positive relationship with all the mentioned parameters [Tables 5,6].

Table 4. Relation between platelet indices and troponin T & pro-BNP.

Platelet indices	Troponin T		pro BNP
Platelet indices	Pearson correlation	P value	Pearson correlation	P value
MPV	0.092	0.269	0.145	0.115
Plateletcrit	0.098	0.239	0.331	0.000
PDW	0.091	0.277	-0.015	0.867

Table 5. Relation between platelet indices and severity of ventricular dysfunction.

Platelet indices	Ventricular dysfunction
Platelet indices	Absent	Mild	Moderate	Severe	P value
MPV (fL)	8.26	8.50	8.59	8.12	0.312
Plateletcrit (%)	0.2086	0.2247	0.2308	0.2523	0.153
PDW (%)	16.58	16.68	16.75	16.77	0.850

Table 6. Relation between platelet indices and severity of coronary heart disease and arrhythmia.

Platelet indices	Severity of coronary artery disease				Arrhythmia
Platelet indices	Single	Double	Triple	P value	Present	Absent	P value
MPV (fL)	8.36	8.38	8.38	0.990	8.41	8.38	0.907
Plateletcrit (%)	0.2087	0.2229	0.2256	0.370	0.2666	0.2151	0.006
PDW (%)	16.65	16.64	16.63	0.994	16.96	16.62	0.229

Analysis of the relationship between platelet indices and other risk factors of coronary artery disease, such as diabetes mellitus (represented by HbA1c) and dyslipidemia (lipid profile), showed that MPV had a positive relationship with HbA1C and the entire lipid profile, while PDW showed a positive relationship with only Hba1C and triglycerides. Plateletcrits had a positive relation with Hba1C and total cholesterol [Table 7].

Table 7. Relation between platelet indices and glycemic status and lipid profile.

Platelet indices		HbA1c	Total cholesterol	Triglyceride	HDL	LDL
MPV	Pearson correlation	0.199	0.231	0.100	0.043	0.221
MPV	p value	0.018	0.006	0.234	0.611	0.008
Plateletcrit	Pearson correlation	0.097	0.728	-0.035	-0.034	-0.020
Plateletcrit	p value	0.251	0.029	0.675	0.689	0.813
PDW	Pearson correlation	0.073	-0.011	0.120	-0.006	-0.009
PDW	p value	0.391	0.899	0.153	0.945	0.911

Discussion

Acute coronary syndrome refers to STEMI, NSTEMI, and unstable angina. Myocardial infarction is defined as “myocardial cell death due to prolonged ischemia.”⁹

The first ultrastructural alterations include reduced cellular glycogen, loosened myofibrils, and sarcolemmal disruption, which can occur within 10–15 min after the onset of ischemia.¹⁰ Mitochondrial anomalies can be observed by electron microscopy as soon as 10 min after cardiac blockage and are progressive.¹¹ Necrosis proceeds from the subendocardium to the subepicardium over several hours in an experimental setting. An increase in collateral flow, decreased drivers of cardiac oxygen demand, and intermittent occlusion or reperfusion that may prepare the heart can all add to the length of time.

Significance is that when reperfusion therapy is administered promptly, it helps to prevent myocardial ischemia.¹²^–¹⁴ Cardiac troponins I (cTnI) and T (cTnT) are components of the contractile machinery of myocardial cells and are found virtually exclusively in the heart.²^,³

Injuries to non-cardiac tissues have not been linked to an increase in cTnI levels. This situation is more complicated for cTnTs. Biochemical evidence suggests that the cardiac troponin T assay detects proteins expressed by damaged skeletal muscle, implying that cTnT increases could come from skeletal muscle in some cases.¹⁴^–²¹ The preferred biomarkers for assessing myocardial damage are cTnI and cTnT, and it is recommended that high-sensitivity cardiac troponin assays be used in clinical practice.²^–⁵ Other biomarkers, such as CK-MB, have lower sensitivity and specificity.⁶ Myocardial injury is said to be present when the levels of cardiac troponin in the blood are above the 99th percentile of the upper reference limit. Injury may be acute, as demonstrated by a “newly found dynamic rising and/or falling level of cTn values above the 99th percentile URL, or chronic, as evidenced by continuously elevated cTn levels”.²^–⁵

The commonly measured platelet indices are the mean platelet volume (MPV), plateletcrit (PCT), and platelet distribution width (PDW). The mean platelet volume is a measure of the platelet volume measured in femtolitres, whereas PDW and PCT are presented as percentages. Plateletcrit refers to the volume occupied by platelets in blood. PDW is an indicator of volume variability in platelet size.

Regarding the role of platelet indices in acute coronary syndrome, larger and hyperactive platelets play a pivotal role in accelerating the formation and propagation of intracoronary thrombi, leading to acute thrombotic events. Larger platelets are enzymatically and metabolically active and have higher thrombotic ability than smaller platelets.⁷^,²²^,²³

We evaluated the diagnostic and prognostic significance of platelet indices in ACS, considering the function of platelets in the pathophysiology of the disease.

MPV in ACS

The literature shows that MPV is higher in patients with myocardial infarction than in those with stable angina pectoris and healthy controls, suggesting that MPV is a risk factor for the severity of coronary artery disease [Table 8].²⁴^–²⁹ In our study, MPV is significantly higher among ACS cases as compared to controls with p value 0.006 and mean difference of 0.35 fL (8.38 fL vs 8.03 fL), suggesting that it may be used as a diagnostic marker of ACS. Regarding MPV as a prognostic marker, it was found to have a positive correlation with trop T, pro-BNP and presence of arrhythmia.

Table 8. Results of other similar studies.

	Present study	Akula S P et al.²⁴	Gururajaprasad et al.²⁵	Cost a sc et al.²⁶	Assiri AS et al.²⁷	Pal R et al.²⁸	Yilmaz M B et al.²⁹
Country of origin	India	India	India	Brazil	Saudi Arabia	India	Turkey
Year of publication		2017	2018	2015	2012	2014	2008
Sample size	290	120	300	83	261	215	336
MPV (fL) (cases vs controls)	8.38 vs 8.03	11.31 vs 10.5	10.5±0.76 vs 9.4±0.7	9.6±0.9 vs 8.1±0.6	8.99±1.5 vs 8.38±0.51	11.44±1.23 vs 9.91±1.275	10.4±0.6 vs 8.9±0.7
P value	0.006	0.04	<0.001	<0.01	0.009	<0.001	0.001
Plateletcrit(%)(cases vs controls)	0.2198 vs 0.2158	0.2217 vs 0.144	Not assessed	0.16±0.1 vs 0.19±0.1	Not assessed	Not assessed	Not assessed
P value	0.585	<0.0001		>0.05
PDW(%)(cases vs controls)	16.65 vs 16.60	17.34 vs 15.21	12.1±1.68 vs 9.8±1.4	16.7±2.8 vs 14.1±1.7	15.88±1.5 vs 11.96±1.8	Not assessed	Not assessed
P value	0.160	<0.0001	<0.0001	<0.01	.001

However none of them were of statistical significance.

PCT in ACS

Studies have shown that higher PCT levels are observed in patients with ACS and are associated with worse prognosis [Table 8]. Our study also noted that plateletcrit was higher among cases but not statistically significant. However, the plateletcrit was the only platelet index that was found to have a positive correlation with all the prognostic markers assessed (troponin T, pro-BNP, ventricular dysfunction, presence of arrhythmia, and severity of vessel disease). Thus, we conclude that PCT is a potential prognostic marker in patients diagnosed with ACS but may not be a suitable diagnostic marker.

PDW in ACS

PDW directly measures the variability in platelet size, changes with platelet activation, and reflects heterogeneity in platelet morphology. Under physiological conditions, there is a direct relationship between the MPV and PDW; both usually change in the same direction. In our study, we observed that the PDW was higher in the ACS group, but not significantly higher.³⁰ Among prognostic markers, PDW has been shown to be positively correlated with troponin T, ventricular dysfunction, and the presence of arrhythmia [Table 8].

Comparing platelet indices with other known risk factors, such as diabetes mellitus and dyslipidemia, we found that MPV showed a positive but insignificant correlation with HbA1C and lipid profile. PDW showed a positive correlation only with HbA1C and triglyceride levels. From the results of our study, we can conclude that MPV and PDW are potential diagnostic markers for ACS, with MPV being superior to PDW. PCT was found to be superior to both MPV and PDW. In conclusion, MPV and PDW are potential diagnostic markers of ACS, with MPV being superior to PDW. PCT was found to be superior to both MPV and PDW as a prognostic marker.

Conclusion

We suggest that platelet indices be applied in the following clinical practice methods. In an outpatient setting where an individual with risk factors is presented for routine evaluation, if platelet indices are grossly deranged, then they may be candidates for further evaluation in the form of coronary CT or coronary angiography to rule out underlying coronary artery disease.

In case of an emergency setting with a patient presenting with acute onset symptoms and if ACS is suspected, deranged platelet indices can be used in the periphery where cardiac biomarkers are not available to decide on referral to a higher center. In other words, platelet indices can be used to triage suspected ACS patients. If ACS is confirmed, platelet indices can be used to prognosticate.

Limitations of study

However, there are limitations associated with applying platelet indices in routine practice, and a few limitations of our study have been elaborated. Patients on antiplatelet agents and those with haematological malignancies were excluded from the study.

Ethics and consent

The study was approved by our Institutional Review Board (IRB) known as Kasturba Medical College and Kasturba Hospital Institutional Ethics Committee (reference number: 954/2019) on 19th November, 2019. This study was conducted in accordance with the principles of the Declaration of Helsinki. Written informed consent was obtained from all participants.

Data availability

Underlying data

Figshare: Platelet indices as diagnostic and prognostic markers in acute coronary syndrome, https://doi.org/10.6084/m9.figshare.25999672.³¹

The data contain the three platelet indices (plateletcrit, platelet distribution width, and mean platelet volume) and various other parameters considered, ranging from lipid profile to echocardiography and coronary angiography findings.

Data are available under the terms of the Creative Common Attribution 4.0 International licence (CC-BY 4.0).

Acknowledgments

We would like to thank the Manipal Academy of Higher Education for providing support in performing the study. Permission has been obtained for the same.

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Author details Author details

¹ Department of Medicine, Manipal, Manipal Academy of Higher Education, Kasturba Medical College Manipal, Manipal, Karnataka, India

Gokul Krishnan
Roles: Conceptualization, Investigation, Methodology, Writing – Original Draft Preparation

M Mukhyaprana Prabhu
Roles: Conceptualization, Methodology, Writing – Review & Editing

Weena Stanley
Roles: Methodology, Supervision, Writing – Review & Editing

Competing interests

No competing interests were disclosed.

Grant information

The author(s) declared that no grants were involved in supporting this work.

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Published: 15 Aug 2024, 13:927

https://doi.org/10.12688/f1000research.152404.1

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© 2024 Krishnan G et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Krishnan G, Prabhu MM and Stanley W. Platelet indices as diagnostic and prognostic markers in acute coronary syndrome [version 1; peer review: awaiting peer review]. F1000Research 2024, 13:927 (https://doi.org/10.12688/f1000research.152404.1)

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[1] 1. Rogers WJ, Frederick PD, Stoehr E, et al.: Trends in presenting characteristics and hospital mortality among patients with ST elevation and non-ST elevation myocardial infarction in the National Registry of Myocardial Infarction from 1990 to 2006. Am. Heart J. 2008; 156: 1026–1034. PubMed Abstract | Publisher Full Text

[2] 2. Thygesen K, Mair J, Katus H, et al.: Recommendations for the use of cardiac troponin measurement in acute cardiac care. Eur. Heart J. 2010; 31: 2197–2204. Publisher Full Text

[3] 3. Thygesen K, Mair J, Giannitsis E, et al.: Study Group on Biomarkers in Cardiology of the ESC Working Group on Acute Cardiac Care. How to use high-sensitivity cardiac troponins in acute cardiac care. Eur. Heart J. 2012; 33: 2252–2257. Publisher Full Text

[4] 4. Thygesen K, Alpert JS, Jaffe AS, et al.: Writing Group on the Joint ESC/ACC/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction. Third universal definition of myocardial infarction. Eur. Heart J. 2012; 33: 2551–2567. Circulation 126:2020–2035; J Am Coll Cardiol 2012: 60:1581–1598. Publisher Full Text

[5] 5. Apple FS, Jaffe AS, Collinson P, et al.: on behalf of the International Federation of Clinical Chemistry (IFCC) Task Force on Clinical Applications of Cardiac Bio-Markers. IFCC educational materials on selected analytical and clinical applications of high sensitivity cardiac troponin assays. Clin. Biochem. 2015; 48: 201–203. PubMed Abstract | Publisher Full Text

[6] 6. Goodman SG, Steg PG, Eagle KA, et al.: The diagnostic and prognostic impact of the redefinition of acute myocardial infarction: lessons from the Global Registry of Acute Coronary Events (GRACE). Am. Heart J. 2006; 151: 654–660. PubMed Abstract | Publisher Full Text

[7] 7. Davì G, Patrono C: Platelet activation and atherothrombosis. N. Engl. J. Med. 2007; 357: 2482–2494. Publisher Full Text

[8] 8. IBM Corp: IBM SPSS Statistics for Windows, Version 28.0. Armonk, NY: IBM Corp; 2021. Released.

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Platelet indices as diagnostic and prognostic markers in acute coronary syndrome

Abstract

Background

Methods

Results

Conclusions

Keywords

Introduction

Methods

Study design

Setting

Participants and sample size

Variables

Data sources & bias

Statistical analysis

Results

Table 1. Demographics.

Table 2. Acute coronary syndrome subtypes among cases.

Table 3. Platelet indices among cases and controls.

Table 4. Relation between platelet indices and troponin T & pro-BNP.

Table 5. Relation between platelet indices and severity of ventricular dysfunction.

Table 6. Relation between platelet indices and severity of coronary heart disease and arrhythmia.

Table 7. Relation between platelet indices and glycemic status and lipid profile.

Discussion

MPV in ACS

Table 8. Results of other similar studies.

PCT in ACS

PDW in ACS

Conclusion

Limitations of study

Ethics and consent

Data availability

Underlying data

Acknowledgments

References

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