European Journal of Cardiovascular Medicine

Acute Coronary Syndrome (ACS) encompasses a wide range of coronary artery disorders caused primarily by atherosclerotic plaque rupture, ulceration, or erosion, leading to intraluminal thrombus formation and impaired myocardial perfusion [1]. The resulting ischemia and necrosis of the myocardium cause the release of cardiac enzymes into circulation [2]. Complete vessel occlusion by a ruptured plaque results in ST-elevation myocardial infarction (STEMI), characterized by localized ST-segment elevation on ECG and, if untreated, can progress to transmural infarction. Non-ST elevation acute coronary syndromes (NSTE-ACS), which include NSTEMI and unstable angina, occur due to incomplete or transient vessel occlusion. NSTEMI presents with enzyme elevation, while unstable angina does not, aiding in therapeutic decision-making and prognosis [3,4].

Platelet activation plays a central role in the pathogenesis of ACS. Activated platelets become more spherical and swollen, increasing in volume and mass. This activation leads to the release of free arachidonic acid, which is converted to thromboxane A₂, a potent vasoconstrictor and platelet aggregator that amplifies the inflammatory cascade [5]. Larger platelets, derived from activated megakaryocytes, possess more secretory granules, mitochondria, and bioactive mediators, making them metabolically and enzymatically more active. These platelets release a variety of adhesive proteins, growth factors, and cytokines, all of which contribute to thrombus formation and vascular injury [6].

The mean platelet volume (MPV), which reflects average platelet size, serves as a simple and inexpensive marker of platelet activation [7]. Unlike other platelet function markers, MPV is automatically calculated in routine hematology analyzers, making it an easily accessible diagnostic parameter. Elevated MPV and platelet distribution width (PDW) have been associated with an increased risk of myocardial infarction and can serve as early indicators for ACS, particularly in differentiating ischemic chest pain when traditional biomarkers are inconclusive [8].

Although troponin remains the gold-standard biomarker for myocardial injury, false elevations can occur in conditions like pulmonary embolism, renal failure, myocarditis, and heart failure. Therefore, serial troponin measurements are recommended at presentation and after 3 hours to confirm acute myocardial infarction. A fivefold increase has a 90% positive predictive value for myocardial infarction, whereas a threefold increase has a lower predictive accuracy of 50–60% [9].

Given the central role of platelet activation in ACS, antiplatelet therapy is fundamental to management. Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor such as clopidogrel or ticagrelor is recommended. Clopidogrel, an irreversible inhibitor, has a delayed onset of action, while ticagrelor acts rapidly and reversibly, making it more effective during the acute phase [10]. Current guidelines advocate DAPT for at least one year after ACS or stent placement, with duration adjusted according to bleeding risk and recurrent event profile. Extended therapy benefits high-risk individuals but may increase bleeding complications, while shorter courses may suffice with newer-generation stents [11].

Hence, considering the important role of platelet activation and platelet indices in the pathophysiology of ACS, the present study aimed to evaluate platelet parameters in patients with acute coronary syndrome and compare them with healthy controls to assess their potential role as early diagnostic and prognostic markers.

The present study was conducted at a tertiary care centre. It was designed as a matched case–control analytical study carried out over a period of two years, from December 2023 to January 2025.

The case group comprised patients aged 18 to 60 years presenting to the emergency ward with ACS, including STEMI, NSTEMI, and unstable angina. The control group included healthy, non-diabetic, non-hypertensive individuals who were non-smokers. Subjects were excluded if they had known bleeding disorders, blood dyscrasias, thrombophilic states, pregnancy, sepsis, hepatic or renal disease, a recent major surgery, or were taking drugs that cause thrombocytopenia, including antiplatelet agents. Participants with malignancy, infections causing thrombocytopenia, or platelet counts below 1,00,000/µL were also excluded.

Venous blood samples were collected from the antecubital vein using a 5 mL syringe and transferred into EDTA vacutainers under aseptic precautions. Samples were analyzed using a differentiated automated hematology analyzer for platelet indices and related hematological parameters. The sample size was calculated using the formula,

𝑁=2(𝑍_𝑎+𝑍_𝑏)²𝑆²/𝑑²

Where, 𝑍_𝑎=1.96 at 95% confidence level and 𝑍_𝑏=.84 at 80% power. Based on the combined standard deviation (S) and mean difference (d), the required sample size was 87 subjects per group, making a total of 174 participants.

Data were analyzed using SPSS version 27. The unpaired t-test was applied to compare mean values between cases and controls. A p-value < 0.05 was considered statistically significant

A total of 174 participants were included in the study, with 87 individuals in each group. The overall mean age of the study population was 58.25 ± 5.10 years, with the majority belonging to the 56–60-year age group. Males predominated across both groups, constituting 78% of the total sample. In the case group, 79% were males, while in the control group, 76% were males, indicating a similar gender distribution. The mean ages were comparable between groups (58.16 years in cases vs. 58.33 years in controls), showing no significant demographic difference between them (Table 1).

Table 1. Baseline Characteristics of Study Participants (n = 174)

Among the 87 cases, the presence of comorbidities was common. Diabetes mellitus was observed in 44.8%, hypertension in 39%, and both diabetes and hypertension in 16.2% of participants. This indicates that metabolic and cardiovascular risk factors were highly prevalent in individuals presenting with acute coronary syndrome (Table 2).

Table 2. Distribution of Cases Based on Comorbidities (n = 87)

Based on clinical diagnosis, the cases were categorized into four subtypes. Inferior wall myocardial infarction (IWMI) was the most frequent presentation, seen in 28.7% of patients, followed by anterior wall myocardial infarction (AWMI) in 27.6%, anterolateral wall myocardial infarction (ALWMI) in 17.2%, and NSTEMI in 26.4% (Table 3).

Table 3. Distribution of Cases Based on Diagnosis (n = 87)

Comparison of platelet indices between cases and controls revealed statistically significant differences in several parameters. The mean platelet count (PC) was slightly lower in cases (2.30 ± 0.34) compared to controls (2.43 ± 0.39), showing significance (p = 0.017). The MPV was significantly higher in cases (8.95 ± 0.63) than controls (6.98 ± 0.43) with a highly significant p-value (< 0.001), indicating increased platelet activity in acute coronary syndrome. The platelet crit (Pcrit) was also higher in cases (0.23 ± 0.27 vs. 0.17 ± 0.01, p = 0.024), while platelet distribution width (PDW) showed no significant difference (p = 0.203) between groups (Table 4).

Table 4. Comparison of Platelet Indices Between Cases and Controls

Further subgroup analysis among the cases compared STEMI and NSTEMI. The mean MPV was significantly higher in STEMI patients (9.10 ± 0.61) compared to NSTEMI (8.52 ± 0.49; p < 0.001), suggesting greater platelet activation in the former. However, PC, Pcrit, and PDW did not differ significantly between these subgroups (p > 0.05), indicating that MPV serves as the most sensitive platelet parameter distinguishing STEMI from NSTEMI presentations (Table 5).

Table 5. Comparison of Platelet Indices Between STEMI and NSTEMI (Among Cases)

Platelets play a central role in the pathogenesis of atherosclerosis and its complications such as ischemic heart disease (IHD). During activation, platelets undergo a morphological transformation from a discoid to a spherical shape to increase their surface area and promote aggregation. This activation process is accompanied by an increase in platelet indices such as MPV, PCT, and PDW. PDW reflects the variation in platelet size, and elevated values indicate increased production of larger, more reactive platelets. Several studies have proposed that raised platelet indices may serve as risk factors for CAD and ACS, highlighting their diagnostic and prognostic importance.

In the current study, platelet indices were compared between ACS patients and healthy controls. The mean MPV was significantly higher in the ACS group (8.94 fL) compared to the control group (6.98 fL), with a p-value < 0.001, indicating a strong association between platelet activation and ACS. Similarly, the mean plateletcrit was significantly higher in the ACS group (0.234) compared to controls (0.167), with p < 0.05. However, PDW did not show a statistically significant difference between the two groups. When ACS subtypes were analyzed, STEMI cases (including anterior wall, inferior wall, and anterolateral MI) demonstrated a higher MPV (9.10 fL) compared to NSTEMI (8.51 fL), which was statistically significant (p < 0.05). Platelet count, plateletcrit, and PDW, however, showed no significant intergroup variation. These findings reinforce the hypothesis that MPV, a marker of platelet activation, may serve as a simple and inexpensive indicator of ACS.

The results of this study are consistent with several previous reports. Randheer et al. found that MPV was higher in ACS patients (11.44 fL) compared to non-ACS patients (9.91 fL). Similarly, Pervin et al. observed elevated MPV in ACS cases in comparison to non-ACS, in concordance with our findings. Studies by A. Mathur et al. and A.S. Assiri et al. also demonstrated similar results. Rifat et al. reported a significant difference in MPV between ACS and non-ACS patients (8.7 ± 1 vs 7.9 ± 0.7 fL), while Sermin et al. found slightly higher but not statistically significant MPV values among STEMI patients compared to NSTEMI. Ridavan et al. (2010) and Nurcan et al. (Turkey) both identified MPV as an independent risk factor for acute myocardial infarction. Furthermore, Jasmin et al. (2014) and Pervin et al. (2011) demonstrated that MPV had greater sensitivity and specificity than platelet count in detecting ACS, suggesting its potential role in early diagnosis and risk stratification.

Taken together, both prior literature and the present study emphasize that increased prothrombotic activity can be reflected by elevated platelet indices, especially MPV, which correlates with enhanced platelet aggregation and thrombus formation. These mechanisms contribute significantly to the pathophysiology of unstable angina, myocardial infarction, and stroke. Hence, MPV can serve as an independent hematological marker of cardiovascular risk and a useful adjunct to traditional biomarkers in ACS evaluation.

Limitation: The study’s generalizability is limited due to its purposive sampling method and relatively small sample size. Larger multicentric studies are warranted to validate these findings and establish reference thresholds for platelet indices in ACS diagnosis

The present study demonstrates that platelet indices, particularly MPV and PCT, are significantly elevated in patients with ACS compared to healthy controls, suggesting their potential role as reliable and cost-effective hematological markers of platelet activation and cardiovascular risk. Among ACS subtypes, STEMI patients exhibited higher MPV values than NSTEMI, indicating greater platelet reactivity in more severe presentations. Given that MPV estimation is a simple, inexpensive, and routinely available parameter in automated blood analysis, it can serve as an adjunct diagnostic tool for early identification and risk stratification of ACS, especially in resource-limited settings. Larger multicentric studies are recommended to further establish standardized cut-off values and validate its clinical utility in predicting adverse cardiac events.

Conflict of Interest: None declared

Acknowledgement: None

Funding: None.

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