Marker Of Platelet Reactivity Research Articles

Increased Platelet Reactivity and Proinflammatory Profile Are Associated with Intima-Media Thickness and Arterial Stiffness in Prediabetes.

Alterations of glucose homeostasis are associated with subclinical vascular damage; however, the role of platelet reactivity in this process has not been fully investigated. In this cross-sectional study, we evaluated the correlation between markers of platelet reactivity and inflammation and markers of vascular disease in subjects with prediabetes. Markers of platelet reactivity such as 11-dehydro-thromboxane B2 urinary levels (11-dh-TXB2) and mean platelet volume (MPV) and inflammatory indexes such as platelet-to-lymphocyte ratio (PLR) were evaluated in subjects with prediabetes (n = 48), new-onset type 2 diabetes (NODM, n = 60) and controls (n = 62). Furthermore, we assessed the cardiovascular risk profile of the study population with arterial stiffness and quality intima–media thickness (qIMT). Subjects with prediabetes and NODM exhibited higher 11-dh-TXB2 urinary levels and MPV and a proinflammatory profile with an increased PLR, high-sensitivity C-reactive protein, ferritin and fibrinogen. Furthermore, after multiple regression analyses, we found that urinary 11-dh-TXB2 was one of the major determinants of IMT and arterial stiffness parameters. In conclusion, subjects with prediabetes exhibit increased platelet reactivity as well as a proinflammatory profile. Furthermore, this condition is associated with early markers of cardiovascular disease.

Baseline mean platelet volume is a strong predictor of major and life-threatening bleedings after transcatheter aortic valve replacement

Bleeding following transcatheter aortic valve replacement (TAVR) has important prognostic implications. This study sought to evaluate the impact of baseline mean platelet volume (MPV), a routinely used marker of platelet reactivity, on bleeding events in a contemporary real-world TAVR cohort. Patients undergoing TAVR between February 2010 and May 2019 with available preprocedural MPV were included. Low MPV (L-MPV) was defined as MPV ≤ 10 fL and high MPV (H-MPV) as MPV > 10 fL. The primary endpoint was the occurrence of major/life-threatening bleeding complications (MLBCs) at one year follow-up. Among 1,111 patients, 398 (35.8%) had L-MPV and 713 (64.2%) had H-MPV. The rate of MLBCs at 1 year was higher in L-MPV patients compared with H-MPV patients (22.9% vs. 17.7% respectively, P = 0.034). L-MPV was associated with vascular access-site complications (36.2% vs. 28.9%, P = 0.012), early (< 30 days) major bleeding (15.6% vs. 9.4%, P < 0.01) and red blood cell transfusion > 2 units (23.9% vs. 17.5%, P = 0.01). No impact of baseline MPV on overall death, cardiovascular death and ischemic events (myocardial infarction and stroke) was evidenced. Multivariate analysis using Fine and Gray model identified preprocedural hemoglobin (sHR 0.84, CI95% [0.75–0.93], P = 0.001), preprocedural L-MPV (sHR 1.64, CI95% [1.16–2.32], P = 0.005) and CT-ADP post-TAVR (sHR 2.71, CI95% [1.87–3.94], P < 0.001) as predictors of MLBCs (Fig. 1, Table 1). Preprocedural MPV was identified as an independent predictor of MLBCs one year after TAVR, regardless of the extent of platelet inhibition and primary hemostasis disorders. MPV should be regarded as a simple, common and valuable biomarker of bleeding prediction after TAVR.

The relationship between mean platelet volume and albuminuria in patients with type 2 diabetes mellitus

Background&aimMean platelet volume (MPV) is suggested as a marker of platelet reactivity and tendency for thrombosis and microvascular complications like albuminuria in patients with type 2 DM. We aimed to measure the MPV in patients with type 2 DM and its correlation with albuminuria, body mass index (BMI), duration of DM, hypertension (HTN), stroke, ischemic heart disease (IHD), and HbA1c level. MethodsA cross sectional study included 100 patients with type 2 DM ≥ 18 y of both genders who were randomly selected from the medical units of Baghdad Teaching Hospital. After taking verbal consents; MPV was measured&correlated with aimed variables. Diabetics with HbA1c ≤ 7% were considered as having adequate control while those with (HbA1c) > 7% as having poor control. Albumin creatinine ratio (ACR) in urine was measured and classified into normal, moderately and severely increased. Odds ratios with 95% CI were calculated and P ≤ 0.05 was considered as statistically significant. ResultsThe mean MPV was 7.7 fl ± 1.2. Regarding ACR, 42% had normal level, 37% with moderately increased and 21% had severely increased level. Regarding HbA1c, 68% were having poorly controlled DM. Mean platelets’ count and MPV were higher in the uncontrolled group with a statistically significant association. There was a statistically significant positive correlation between MPV and albuminuria, duration of DM, HTN, IHD, Stroke, BMI, HbA1c, and platelets count. ConclusionsThe mean MPV was statistically significantly higher in the uncontrolled DM group and there was a statistically significant positive correlation between MPV and albuminuria.

2218-PUB: Increased Platelet Reactivity Is Associated with Inflammation and Arterial Stiffness in Subjects with Prediabetes

We investigated markers of platelet reactivity and low-grade inflammation, and their association with early markers of vascular disease in subjects with prediabetes and new onset type 2 diabetes (NODM). Methods: 121 subjects without history of diabetes were stratified into 3 groups according to glycemic status: controls (n=41), prediabetes (n=42) and NODM (n=39). Platelet reactivity was evaluated as 11-dehydro thromboxane B2 urinary levels (TXB2), mean platelet volume (MPV) and platelet/lymphocytes ratio (PLR); cardiovascular risk was evaluated with arterial stiffness [pulse wave velocity (PWV), Augmentation pressure (AP), Subendocardial viability ratio (SEVR)] and intima media thickness (IMT). Results: Subjects with prediabetes exhibited: higher TXB2 urinary levels (10.7 ± 4.8 vs. 6.4 ± 1.8 pg/mg creatinine, p&amp;lt;0.05), PLR (143.7 ± 43 vs. 106.1 ± 26.7, p&amp;lt;0.05) and lower MPV (8.7 ± 0.7 vs. 9.5 ± 1.1 fl, p&amp;lt;0.05). Prediabetes showed higher fibrinogen and C creative protein (CRP) serum levels (333.2 ± 63 vs. 310.6 ± 58 mg/dL, p&amp;lt;0.05; 0.34 (0.11-0.47) vs. 0.14 (0.08-0.27) mg/dL, p&amp;lt;0.05, respectively). Subjects with prediabetes exhibited increased PWV, AP and IMT (8.1 ± 0.9 cm/sec vs. 7.5 ± 1.5, p&amp;lt;0.05; 13.2 ± 9.5 mmHg vs. 11.2 ± 4.6, p&amp;lt;0.05 and 710.2 ± 93.4 vs. 659 ± 93.1 μm, p&amp;lt;0.05, respectively) and decreased SEVR (159.4 ± 11 vs. 171.8 ± 32.3, p&amp;lt;0.05) compared with controls. No differences were found between prediabetes and NODM subjects regarding platelet reactivity and cardiovascular risk markers.TXB2 urinary levels were independently associated with hs-CRP, fibrinogen and HbA1c in multiple regression analysis. In simple regression analysis AP, PWV and SEVR showed a significant association with TXB2 urinary levels (r=0.32, p&amp;lt;0.05, r=0.16, p&amp;lt;0.05 and r=0.26 p&amp;lt;0.05 respectively). Conclusions: Subjects with prediabetes showed increased platelet reactivity and inflammation markers. These alterations were associated with early markers of cardiovascular disease. Disclosure A. Di Pino: None. F. Urbano: None. R. Scicali: None. S. Piro: None. A. Rabuazzo: None. F. Purrello: None. Funding University of Catania

Impact of long-term therapy with acetylsalicylic acid on immature platelet count: a single-centre cohort study.

: Acetylsalicylic acid (ASA) represents one of the most widely used pharmacological treatments for the prevention of atherothrombotic events. However, its use in low-risk patients is still debated, due to the complex balance between benefits and bleeding complications, therefore requiring new tools for the assessment of cardiovascular risk. Immature platelet count (IPC) has been suggested as a marker of platelet reactivity and turnover, thus potentially reflecting the progression of the chronic atherothrombotic vascular damage, which could be prevented by ASA. However, no study has evaluated, so far, the impact of long-term therapy with ASA on the IPC among patients undergoing coronary angiography, which was the aim of the present study. We included patients from a single centre. Significant coronary artery disease (CAD) was defined as at least one-vessel stenosis more than 50%. Immature platelet fraction (IPF) levels were measured by routine blood cells count (a Sysmex XE-2100) in patients naive or chronically treated with ASA at admission. Among 1475 patients, 464 (31.5%) were ASA-naive. Patients on long-term antiplatelet therapy were more often men (P < 0.001), with a higher prevalence of cardiovascular risk factors and CAD. The mean levels of IPC did not differ between ASA-naive and treated patents (8 ± 5.3 vs. 7.8 ± 4.9, P = 0.48). Similar results were obtained when considering IPC distribution across tertiles, as ASA therapy did not result as an independent predictor of IPC levels above the third tertile (≥8.6 × 10/ml) [adjusted odds ratio (95% confidence interval) = 0.96 (0.63-1.48), P = 0.87]. Results were confirmed in major higher risk subgroups of patients. The present study shows that among high-risk patients undergoing coronary angiography, the long-term therapy with ASA does not affect the levels of IPC.

Impact of metabolic syndrome on mean platelet volume and its relationship with coronary artery disease.

Platelets represent one of the main actors involved in pathogenesis of coronary artery disease (CAD). Mean platelet volume (MPV) has been proposed as marker of platelet reactivity and thrombotic risk. However, still debated is whether higher MPV constitutes an independent determinant of CAD or just the consequence of an association with several cardiovascular risk factors. Therefore, the aim of the present study was to assess the impact of metabolic syndrome (MetS), on MPV and its relationship with angiographically defined CAD. Consecutive patients undergoing coronary angiography were included. Admission samples were collected for MPV and chemistry assessment. MetS was defined according to IDF-criteria. Significant CAD was defined as at least 1 vessel stenosis >50%, while severe CAD as left main and/or 3-vessel disease, as evaluated by quantitative coronary angiography. We included 4730 patients, among them 2167 (45.8%) had MetS. Patients with MetS were older (p<0.001), more often females (p<0.001), and displayed higher BMI, higher prevalence of hypercholesterolemia, renal failure, hypertension, diabetes mellitus, history of myocardial infarction (MI), previous PCI (p<0.001, respectively), previous CABG (p=0.002),treatment with ACE inhibitors, ARB, beta-blockers, nitrates, statins, ASA, calcium channel blockers, diuretics (p<0.001, respectively), higher values of glycemia, HbA1c, fibrinogen (p<0.001, respectively), creatinine (p=0.01), uric acid (p=0.02), and lower values of hemoglobin (p=0.001),total-cholesterol, LDL-cholesterol, and HDL-cholesterol (p<0.001, respectively). MetS patients showed a higher prevalence of CAD (p=0.002) and severe CAD (p=0.01). MPV values were slightly higher in patients with MetS (10.91±1.01 vs. 10.84±1.03 fL, p=0.02), although MetS did not emerge as an independent predictor of higher MPV values (above 4th quartile; adjusted OR OR[95%CI]=1.01[0.84-1.22], p=0.93). When metabolic syndrome patients were analyzed according to MPV quartiles, higher MPV values did not result as an independent predictor of CAD (adjusted OR[95%CI]=0.79[0.61-1.03], p=0.08) and severe CAD (adjusted OR[95%CI]=0.82 [0.65-1.03], p=0.084). Results did not change when applying the new harmonized definition of MetS. This study shows that among patients undergoing coronary angiography MetS is not an independent predictor of higher MPV. Moreover, among MetS patients, larger-sized platelets are not associated to the prevalence and extent of CAD.

JAK2V617F Mutation and Thrombosis History Are Determinants of Mean Platelet Volume (MPV) in Essential Thrombocythemia Patients

Introduction and aim: Persistently enhanced platelet activation has been described in patients with myeloproliferative neoplasms, i.e. essential thrombocythemia (ET) and polycythemia vera (PV), which carry a high thrombotic risk. Different studies suggest that mean platelet volume (MPV) and immature platelet fraction (IPF) can serve as useful markers of platelet activation and increased thrombosis rate in various diseases. In a previous study of ET and PV patients, we demonstrated that JAK2V617F mutation and hydroxyurea (HU) treatment determine the IPF parameters (Panova-Noeva et al, Blood 2011). In this study of ET patients, we aimed to investigate on whether MPV values are influenced by pathogenic factors, such as JAK2V617F mutation, previous thrombotic events, HU treatment, and features of platelet activation.Methods: Eighty-nine consecutive patients with ET (56F/33M; median age 60 yrs) were recruited after written informed consent. Venous blood samples were collected at enrollment and clinical data recorded. Ninety healthy subjects acted as a control group. The mutational status was as follows: 46 patients (51.6%) were JAK2V617F+, 23 (25.8%) CALR+, and 3 (3.4%) MPL+. Thirty eight patients were receiving HU cytoreductive therapy plus ASA, 6 patients HU alone, and 20 patients none of these drugs. Fifteen patients (16.8%) had a positive history of thrombosis. MPV was measured by an automated hematology analyzer (CELL-DYN Ruby System). Platelet surface P-selectin was measured by flow cytometry. Plasma levels of platelet-released proteins, i.e. soluble (s)P-selectin, sGPV, PF4, βTG, were measured by commercial ELISA (Stagò, France).Results: The study shows that in ET patients, the MPV values were inversely related to platelet count (p=0.005, by a multivariate analysis). The analysis according to mutational status indicates that MPV was greater in JAK2V617F+ carriers compared to JAK2 wild type (p<0.05) or other mutation carriers. In addition, MPV was greater in subjects with a positive history of thrombosis versusthose without (p<0.05) and results remained significant after multivariate analysis (p<0.05). Differently, HU treatment did not correlate with MPV values. Also, the platelet activation parameters, including the levels of platelet surface P-selectin and the plasma circulating markers, i.e. sP-selectin, sGPV, PF4, βTG, showed no relation with MPV.Conclusions: Our data provide evidence that the presence of JAK2V617F mutation or of a positive history of thrombosis are linked to MPV values in ET patients, which might contribute to the prothrombotic phenotype in these patients. In view of the increasing importance of MPV as a marker of platelet reactivity, prospective studies are warranted to evaluate the usefulness of MPV as a cellular marker to predict thrombosis in MPN patients.Project funded by "AIRC-IG2013" grant Nr. 14505 from the "Italian Association for Cancer Research" (A.I.R.C.). DisclosuresFalanga:Pfizer: Speakers Bureau; Aspen: Speakers Bureau; Janssen: Speakers Bureau.

Impact of renal function on mean platelet volume and its relationship with coronary artery disease: A single-centre cohort study

BackgroundMean platelet volume (MPV) has been proposed as a marker of platelet reactivity and cardiovascular disease. Chronic kidney disease (CKD) significantly favors the occurrence of cardiovascular events, by increasing the circulating levels of a wide spectrum of pro-oxidant and pro-thrombotic mediators. However, opposite alterations of platelet function, both enhanced aggregability and increased bleeding diathesis have been reported in these patients, with contrasting results on the effects of renal function on MPV and coronary artery disease, that were assessed in present study. MethodsIn patients undergoing coronary angiography, MPV and renal function (serum creatinine and estimated Glomerular Filtration Rate, eGFR, by MDRD formula) were assessed at admission. Coronary artery disease (CAD) was defined as a stenosis >50% in at least 1 coronary vessel, while severe CAD as left main or trivessel disease. ResultsAmong 3712 patients, 1044 (28.1%) had chronic kidney disease. CKD was related with age, female gender, diabetes and glycemic control, history of myocardial infarction, cerebrovascular accidents, coronary artery bypass grafting and left ventricular dysfunction or arrhythmias as indication to angiography, therapy with angiotensin-receptor blockers, nitrates, diuretics and calcium-antagonists, but lower rate of smoking, lower fibrinogen levels, haemoglobin, total and HDL cholesterol (p<0.001, respectively). CKD patients displayed increased severity and complexity of CAD (p<0.001) and significantly larger platelet volume (p<0.001), with CKD resulting as independent predictor of MPV above the median (≥10.85fl; Adjusted OR[95%CI]=1.56[1.23,1.99], p=0.002). Moreover, in the 1044 patients with renal failure, higher platelet volume (above the median value; ≥10.85fl) was associated with age (p=0.05), haemoglobin levels and platelet count (p<0.001), but not to a higher prevalence or extent of coronary artery disease (CAD: adjusted OR[95%CI]=0.80[0.58–1.09], p=0.16; severe CAD, adjusted OR[95%CI]=1.07[0.81–1.41], p=0.65). ConclusionsHigher values of MPV are observed among patients with chronic kidney disease, inversely relating to eGFR. However, larger platelet size does not contribute to explain the increased severity of coronary artery disease observed among these patients.

Reduced spontaneous platelet aggregation: a novel risk factor for adverse pregnancy outcome

ObjectiveSpontaneous platelet aggregation has not been adequately assessed as a potential risk factor for adverse outcomes in pregnancy. Therefore the objective of this study was to assess spontaneous platelet aggregation (SPA), measured via a novel functional assay, as a risk factor for hypertensive disease and intra-uterine growth restriction (IUGR). Study designThis was a prospective longitudinal study. Spontaneous platelet aggregation was assessed as a marker of platelet reactivity using a modification of light transmission aggregometry. Platelet reactivity was assessed in four groups: non-pregnant healthy female volunteers (n=30), longitudinally in normal uncomplicated pregnancy (n=50), hypertensive disorder (n=40) and IUGR (n=30). The mean percentage SPA was plotted and compared across all groups. ResultsSpontaneous platelet aggregation was significantly reduced in the first trimester compared to the non-pregnant group (p-value=0.003). The mean aggregation for the hypertensive group was 1.9%, (95% CI −0.08 to 4.02) and for the IUGR group was 1.6%, (95% CI −0.6 to 3.72). Platelet aggregation in the hypertensive group was significantly reduced compared to the normal pregnant group (p<0.05). Spontaneous platelet aggregation was also reduced in the IUGR group compared to normal pregnancy (p<0.05). ConclusionThis study demonstrates that a reduction of spontaneous platelet aggregation may be a novel risk factor for adverse pregnancy outcomes such as pre-eclampsia and IUGR. The most clinically significant finding is that SPA is significantly lower in pregnancies complicated by hypertension and IUGR compared to those who had a normal pregnancy outcome. Further studies should be carried out to asses if spontaneous platelet aggregation may be a clinically useful tool for the prediction of pre-eclampsia and IUGR.

Brak wpływu stopnia zwężenia zastawki aortalnej na standardowe parametry płytek krwi — kluczowa rola innych czynników ryzyka sercowo-naczyniowego

Introduction. Calcification of the aortic valve, the main component of degenerative aortic stenosis (AS), results in turbulent blood flow, higher shear stress and may have an effect on the platelet (PLT) parameters. Platelet function and size, which are easily measured automatically during a complete blood count, are proposed as markers of platelet reactivity and risk factors for cardiovascular diseases. Material and methods. 143 patients with AS (mean age: 70 ± 13 y., males 76/53%) were enrolled into the study and divided according to the AS severity: severe AS (n = 89; males 43/48.3%; age IQR: 70 [63–75] y.) and non-severe AS (n = 54; males 63/61.1%; age IQR: 70 [62–76] y.). The clinical data were collected and analyzed with special attention being paid to the cardiovascular risk factors, concomitant diseases (coronary artery disease [CAD], diabetes mellitus, arterial hypertension, obesity). Laboratory tests and echocardiography were assessed in all subjects. Routine admission complete blood cell count was obtained — PLT count, mean PLT volume (MPV), PLT distribution width (PDW) and percentage of giant PLT (giant PLT%) were analyzed. Results. There were no differences between the PLT count, MPV, PDW and giant PLT% when comparing the group with severe AS to the non-severe AS group. Multivariate analysis showed a significant effect of CAD coincidence (β = –0.2, SE = 0.09, p = 0,03) and active smoking (β = –0.2, SE = 0.09, p = 0.03) on the PLT count; obesity (β = 0.2, SE = 0.09, p = 0.03) and CAD (β = –0.2, SE = 0.09, p = 0.03) on MPV; obesity (β = 0.21, SE = 0.09, p = 0.02), thienopyridines (β = 0.19, SE = 0.09, p = 0.03) and LMWH intake (β = 0.21, SE = 0.09, p = 0.02) on PDW; and similarly, obesity (β = 0.23, SE = 0.09, p = 0.01), thienopyridines (β = 0.18, SE = 0.09, p = 0.046) and LMWH intake (β = 0.23, SE = 0.09, p = 0.01) on giant PLT%. Conclusions. Aortic stenosis severity has no effect on PLT count and morphology that are automatically measured. The coincidence of standard cardiovascular risk factors and the CAD effects on the PLT parameters that are established during a standard complete blood count.

Platelet Larger Cell Ratio and High-on Treatment Platelet Reactivity During Dual Antiplatelet Therapy

Low response to antiplatelet agents has been associated to an increased risk of thrombotic complications and recurrent ischemic events. Platelet size has been proposed as a potential marker of platelet reactivity. Therefore, the aim of the present study was to evaluate the impact of platelet Larger Cell Ratio (p-LCR) on platelet aggregation and the prevalence of residual high-on treatment platelet reactivity (HRPR) in patients receiving dual antiplatelet therapy (DAPT) after a recent acute coronary syndrome or coronary revascularization. Patients treated with DAPT (ASA and clopidogrel or ticagrelor) were scheduled for platelet function assessment at 30-90 days post-discharge. HRPR was considered for ASPI test >862 AU*min (for ASA) or ADP test values ≥417 AU*min (for ADP-antagonists) using impedance aggregometry. Our population consisted of 530 patients receiving DAPT, who were divided in tertiles according to values of p-LCR (< 27.6; 27.6-34.7; ≥34.7 l). p-LCR was related with use of beta-blockers (p = 0.02) and statins (p = 0.002), and inversely with acute presentation (p = 0.05). Higher platelet count (p < 0.001) and haemoglobin levels (p = 0.001) were observed in higher p-LCR tertiles. The prevalence of HRPR for ASA was low and not significantly different across tertiles of p-LCR (1.1 vs 1.1 vs 1.7%, p = 0.66; adjusted OR[95%CI] = 1.68[0.66-4.29], p = 0.27). Moreover, p-LCR did not influence the occurrence of HRPR for ADP-antagonists (24.4% vs 20.9% vs 25.6 %%, p = 0.80, adjusted OR[95%CI] = 0.88[0.67-1.17], p = 0.38) and similar results were obtained when considering separately patients receiving clopidogrel (adjusted OR[95%CI] = 1.21[0.86-1.69], p = 0.29) or ticagrelor (adjusted OR[95%CI] = 1.17[0.69-2], p = 0.56). In patients receiving DAPT for coronary artery disease, p-LCR does not impact platelet reactivity. Larger platelets did not influence the prevalence of high-on treatment platelet reactivity with the antiplatelet agents ASA, clopidogrel or ticagrelor.

Impact of age on mean platelet volume and its relationship with coronary artery disease: A single-centre cohort study

Elderly patients represent a high risk category among subjects with atherosclerosis, due to the presence of comorbidities and suboptimal response to antiplatelet drugs. Mean platelet volume (MPV) has been indicated as a marker of platelet reactivity, with contrasting data on its role on coronary artery disease. Aim of the present study was to evaluate the impact of age on the MPV and its role on the extent of coronary artery disease (CAD). MethodsOur population is represented by a cohort of 3750 patients undergoing coronary angiography. Elderly were defined according to age≥75years. MPV was measured at admission. Significant coronary artery disease was defined as a stenosis >50% in at least 1 coronary vessel, while severe CAD was defined as left main and/or three-vessel disease. ResultsA total of 1170 out of 3750 (31.2%) patients were ≥75years old. Advanced age was associated with female gender (p<0.001), hypertension (p<0.001), renal failure (p<0.001), previous myocardial infarction (p=0.03) coronary artery bypass grafting (p<0.001) indication to angiography (p<0.001), therapy with angiotension-receptor blockers, (p=0.003), nitrates, diuretics and calcium-antagonists (p<0.001), serum creatinine (p<0.001), fibrinogen (p<0.001) and C reactive protein (p=0.02), but inversely to percutaneous coronary interventions (p=0.02), dyslipidemia, family history of CAD and smoking (p<0.001, respectively), use of statins (p=0.02) and beta blockers (p=0.003), haemoglobin, total cholesterol and triglycerides (p<0.001, respectively), white blood cells (p=0.009) and platelet count (p=0.006).Elderly patients displayed a significantly larger platelet volume (p<0.001), with a direct linear relationship between age and the MPV (r=0.08, p<0.001), with age being confirmed as an independent predictor of larger MPV (≥10.85fl) at multivariate analysis (adjusted OR [95% CI]=1.18 [1.01–1.40], p=0.04).Among the elderly, MPV value above the median (≥10.85fl) was not associated with a higher prevalence of coronary artery disease (77.3 vs. 79.4%, p=0.39, adjusted OR [95% CI]=0.94 [0.66–1.33], p=0.71), or higher prevalence of severe CAD (35.2 vs. 32.4%, p=0.28, adjusted OR [95% CI]=1.34 [0.99–1.82], p=0.06). ConclusionAdvanced age was directly associated with larger mean platelet volume that, however, did not contribute to explain the higher prevalence and extent of coronary artery disease observed in elderly patients.

Is mean platelet volume itself a sufficient indicator of coronary syndrome X?

Dear Editor, We read with deep interest the paper “Evaluation of the mean platelet volume in patients with cardiac syndrome X” by Demirkol et al. (1). The authors (1) aimed to evaluate the mean platelet volume (MPV) in patients with cardiac syndrome X (CSX) and compare patients with coronary artery disease (CAD) with a control group. We have a minor criticism concerning their methodology. Although statistical significance was defined as p<0.05 and the p-values of MPV were given, the p-values of all variables should have been provided in the paper (1). It seems that some of the variables are not compatible with a normal distribution. However, the continuous variables were only reported as mean±standard deviation (SD). In addition, the authors (1) used a one-way analysis of variance (ANOVA) or Kruskal–Wallis test to compare the variables. ANOVA is used to analyze the means of two or more samples. The Kruskal–Wallis test is the nonparametric equivalent of the ANOVA test. The statistical test used for each variable in the study is thus unclear (1). CSX is an angina with signs associated with decreased blood flow to the heart tissue but with normal coronary arteries. A number of systemic microvascular abnormalities, including endothelial cell dysfunction, diffuse atherosclerosis, and systemic inflammation, result in reduced blood flow (2,3). Platelets play a key role in atherothrombosis and inflammation. MPV, an index of platelet function, is a potential marker of platelet reactivity. Therefore, recent studies have focused on platelet function and inflammatory markers to determine their importance in cardiovascular diseases, including CSX (4,5). Most conditions, including traditional risk factors (e.g., hypertension, atherogenic lipoproteins, obesity, and hyperglycemia) and many inflammatory conditions (e.g., infection and inflammatory diseases), can influence MPV (4,5). However, the authors (1) did not exclude local or systemic infections or any previous history of infection (particularly <3 months). In addition, the authors (1) did not analyze inflammation markers, such as C-reactive protein (CRP), even though their role in inflammation has been previously reported in CAD. It is still unclear whether MPV measurement is the best method to determine the inflammation in patients with CSX. If other proven inflammatory markers (in addition to MPV) had been screened and were found to correlate with the MPV of these patients, the conclusions would have been more definitive. Therefore, the MPV should be evaluated together with the other serum inflammatory markers. Although the authors (1) did not include other markers relevant to CSX in their paper, we agree with their follow-up letter that suggests that MPV itself (without other inflammatory markers) may not provide comprehensive information about ongoing inflammation (6). Furthermore, in addition to the p values, the exact MPV values for each group should have been provided in order to analyze the entire study group to determine the clinical impact of the MPV. We would like to congratulate the authors (1) for highlighting the efficacy of MPV in patients with CSX. MPV appears to be a novel marker and an important indicator and predictor of atherothrombosis together with traditional risk factors and other proven inflammatory markers. Large-scale prospective clinical studies with these recommendations are now needed.

Relationship of admission mean platelet volume, platelet distribution width and white blood cells with ST resolution in patients with acute ST segment elevation myocardial infarction treated with streptokinase without history of previous cardiovascular surgery

Background:Mean platelet volume (MPV) and platelet distribution width (PDW), markers of platelet reactivity, and white blood cell count (WBC-C), a marker of inflammation, have been shown to be predictive of unfavorable outcomes among survivors of ST elevation myocardial infarction (STEMI). we aimed to evaluate the value of admission of MPV, PDW and WBC-C for the prediction of ST segment resolution, in patient with acute STEMI treated with Streptokinase.Materials and Methods:This cross sectional study conducted on 280 patients with STEMI treated with streptokinase, from August 2009 until August 2011, in Afshar cardiovascular center, Yazd, Iran. Blood samples were obtained on admission in 280 patients with STEMI. According to sum of ST segment resolution and Schroder's method, patients divided two groups ((patients with ST resolution≥ 70% versus group with ST resolution < 70%)). The best cut off value of MPV, PDW and WBC-C for prediction of ST resolution (STR) were identified by using the receiver operating characteristic curve. The optimum cut off level was determined by selecting points of test value that provided the greatest sum of sensitivity and specificity.Results:Of 280 patients enrolled this study, 39.3% of the patients with STR≥70% and in 60.7% with STR<70% were found. Patients in the STR < 70% group had higher admission MPV (10.6 ± 0.8 vs. .9.5 ± 0.8, P = 0.00) and higher PDW (13.8 ± 1.8 vs. 11.8 ± 1.7, P = 0.00)and higher WBC-C (12.1 ± 3.1 vs. 10.5 ± 2.5, P = 0.00) compare with patients with ST resolution ≥ 70%. The best cut off value of MPV for predicting STR < 70%was 10/05 fl (sensitivity 71/8 and specificity 80.9%) and for PDW was 12.85 fl (sensitivity 71.2% and specificity 83.6%) and for WBC-C was 12.65 × 1000 (sensitivity 42.9% and specificity 82.7%). The greatest area under the receiver operating characteristic (ROC) curve and greatest predicting value for ST resolution lower 70% was due to PDW (area = 0.812, P = 0/00).Conclusion:MPV, PDW and WBC-C at admission might be valuable in the prediction of impaired STR and in planning the need for adjunctive therapy to improve outcomes with STEMI treated with Streptokinase. We can speculate that acute STEMI patients having MPV-PDW and WBC-C values above their's cut off patients should be considered for stronger antiplatelet and helps anti inflammation treatment to be able to attain a favorable ST resolution and better clinical outcome.

The safety and efficacy of intracoronary nitrite infusion during acute myocardial infarction (NITRITE-AMI): study protocol of a randomised controlled trial

IntroductionAcute myocardial infarction (AMI) is a major cause of death and disability in the UK and worldwide. Presently, timely and effective reperfusion with primary percutaneous coronary intervention (PPCI) remains the...

015: Relation between platelet activation and inflammation indexes measured on admission and new onset atrial fibrillation in patients with acute myocardial infarction

Platelet activation is present in atrial fibrillation (AF), but there is some debate whether this is due to AF itself and/or to underlying cardiovascular diseases. We aim to determine the association between a marker of platelet reactivity (mean platelet volume (MPV)) and systemic inflammation (CRP) measured on admission, and new onset episode of AF in patients with MI. Prospective cohort of 4994 consecutive patients with AMI. Patients with paroxysmal or persistent AF were excluded. 426 (8.5%) patients were diagnosed with a new onset of AF during the in-hospital-stay (mean stay 3±2 days). These patients were older (75 vs 65, p<0.001), predominantly male, and prevalence of hypertension and diabetes was greater. Also less smoker were found among this group. Despite similar reperfusion strategies, clinical presentation with heart failure and increased heart rate (HR) was more frequently found in patients with AF. Left ventricular ejection fraction (LVEF) was significantly depressed in AF patients (47 vs. 55, p<0.001), among with increased NT-proBNP, admission MPV (8.9 vs. 8.6, p<0.001) and CRP (10.7 vs 5.7, p<0.001). Backward logistic regression analysis (model 1) found that age [OR=1.04, 95%CI (1.031–1.050), p<0.001)], HR [OR=1.016, 95%CI (1.011–1.021), p<0.001)], LVEF [OR=0.979, 95%CI (0.970–0.987), p<0.001)] and MPV [OR=1.182, 95%CI (1.064–1.312), p<0.001)] were independent predictors of AF occurrence. A second backward regression analysis (model 2= model 1+CRP) found that age [OR=1.036, 95%CI (1.026–1.046), p<0.001)], HR [OR=1.013, 95%CI (1.008–1.018), p<0.001)], LVEF [OR=0.977, 95%CI (0.968–0.987), p<0.001)] and CRP [OR=1.003, 95%CI (1.001–1.005), p=0.006)] were independent predictors of AF occurrence after MI. This study suggested that new onset of AF early after MI is rather linked to inflammation induced by myocardial damage or the existing atherosclerotic burden than platelet activation.

Mean Platelet Volume as a Diagnostic Marker for Cardiovascular Disease

After the first description of platelets more than a century ago, the knowledge about their origin and function grew continuously. The development of the impedance method as a completely automated assay allowed integrating mean platelet volume (MPV) measurement as a routine parameter of the complete blood count. This enabled us to focus more on the association of platelet function and size. Since then, many authors described MPV as a marker of platelet reactivity and risk factor for cardiovascular diseases. Hence, the preanalytical variability of this parameter is known from its introduction as standard laboratory value. Unfortunately no preanalytical standards have been implemented. This review shows the high variability in the literature with MPV as a risk factor for cardiovascular disease. After a brief description of the biology of platelets, we provide an in-depth survey of the measurement methods and their drawbacks. Finally, we propose a possible approach to standardization.

Enhanced platelet-derived microparticle formation is associated with carotid atherosclerosis in convalescent stroke patients

Platelets participate in the development and progression of atherosclerosis. During this process they interact with endothelial cells and leukocytes. Therefore, we investigated the associations between carotid atherosclerosis and platelet reactivity markers. The platelet surface expression of P-selectin (CD62P) and the activated GPIIb/IIIa receptor (corresponding to increased binding of PAC-1), as well as the fraction of platelet-derived microparticles (PMPs) prior to and after platelet stimulation with TRAP or ADP, were determined using flow cytometry in 94 subjects in the convalescent phase of ischaemic stroke and in 76 disease controls. The mean common carotid intima-media thickness (CCAmean IMT), maximal common carotid IMT (CCAmax IMT) and maximal bifurcation IMT (BIFmax IMT) were measured bilaterally using B mode, colour Doppler ultrasonography. In stroke subjects IMT within CCA and BIF were greater than in disease controls and the percentage of PMPs prior to and after ex vivo stimulation with agonists was significantly higher than in controls. Multiple regression analysis revealed that PMPs were positively and independently correlated with both CCAmean IMT ( β = 0.23; p < 0.01) and stroke ( β = 0.21; p<0.01), while PAC-1 binding to platelets activated with ADP was negatively and independently associated with CCAmean IMT ( β = −0.29; p<0.001) and atherosclerotic carotid plaque presence ( β = −0.28, p = 0.003). We found a positive association between enhanced PMP formation and atherosclerotic thickening of carotid intima-media or carotid plaque in patients after ischaemic stroke. We demonstrated that diminished expression of active GPIIb/IIIa in the ADP-activated platelets is associated with increased carotid IMT, independently of stroke.

Prognostic significance of mean platelet volume on admission in an unselected cohort of patients with non ST-segment elevation acute coronary syndrome

Mean platelet volume (MPV) has been proposed as a marker of platelet reactivity and cardiovascular risk. Its prognostic significance has not been thoroughly investigated in patients with non-ST elevation acute coronary syndrome (NSTE-ACS). We included 1,041 consecutive patients with NSTE-ACS. Patients were divided in quartiles according to the MPV value on admission (fl) i.e. Q1<7.5; Q2=7.5-8.0; Q3=8.1-8.8; Q4≥8.9. The primary study endpoint was the composite of cardiovascular death and re-myocardial infarction (MI) at one year. Secondary study endpoints were individual cardiovascular death and re-MI. Patients in Q4 were older, had a higher prevalence of previous MI, peripheral artery disease and advanced Killip class compared to patients in Q1-Q3. Elevated MPV levels (Q4) was independently associated with gender, smoking status, platelet count and creatinine level. Overall, 210 patients (20.2%) reached the primary endpoint, 124 (12.1%) died from cardiovascular causes and 125 (12.0%) suffered from re-MI. On multivariable analysis patients in Q4 were at higher risk of primary endpoint (HR=1.41; 95%CI 1.06-1.89; p=0.02) whilst the association with cardiovascular death and re-MI was attenuated. MPV as continuous variable was independently associated with both primary endpoint (HR=1.19; 95%CI 1.06-1.33; p=0.003) and cardiovascular death (HR=1.23; 95%CI 1.06-1.42, p=0.006). The incorporation of MPV into a comprehensive model of risk significantly increased the likelihood ratio chi-square for prediction of both the composite endpoint (p=0.004) and cardiovascular death (p=0.009). Therefore, MPV may be useful to improve risk stratification in NSTE-ACS patients and should be included in future prospective studies evaluating the role of platelet function in promoting cardiovascular events.

Platelet-Large Cell Ratio and the extent of coronary artery disease: results from a large prospective study

Even though platelet volume has been supposed to be indicator of platelet activation, contrasting results have been reported on its relationship with the extent of coronary artery disease (CAD). No data have been so far reported on Platelet-Large Cell Ratio (P-LCR). Thus, the aim of the current study was to investigate whether P-LCR is associated with CAD. We measured P-LCR in 1882 consecutive patients undergoing coronary angiography. Significant CAD was defined as stenosis >50% in at least 1 coronary vessel. We additionally measured Carotid Intima-Media Thickness (IMT) in 359 patients. The relationship between P-LCR and platelet aggregation was evaluated by PFA-100 and Multiplate. Patients with higher P-LCR were older (P=0.038), with larger prevalence of diabetes (P<0.0001), dilated cardiomyopathy or valvular heart disease (P=0.004) and less often family history of CAD (P=0.045), more often on statins (P=0.002), and diuretics (P=0.016). P-LCR was significantly associated with baseline glycaemia (P=0.001) and RBC count (P<0.001), but inversely related to platelet count (P<0.0001). P-LCR was not associated with the prevalence of CAD (adjusted P=0.3) or its severity. In addition, P-LCR was not related to Carotid IMT or platelet aggregation in patients with or without aspirin therapy. This study showed that P-LCR is not related to platelet aggregation, aspirin resistance, the extent of CAD and carotid IMT. Thus, P-LCR can not be considered as a marker of platelet reactivity or a risk factor for CAD.