Roberta Rolla

Azienda Ospedaliero Universitaria Maggiore della Carità, Novara, Piedmont, Italy

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Publications (43)227.6 Total impact

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    ABSTRACT: Background and aim: High residual platelet reactivity (HRPR) is still an important challenge, despite the advent of new potent ADP-antagonists. Therefore it is of extreme importance to identify factors that can influence platelet activation. Serum uric acid (SUA) has been largely addressed in the past as a possible risk factor for coronary artery disease, with a possible association with platelets hyperreactivity. So far no studies have assessed the role of serum uric acid on the response to dual antiplatelet therapy. Therefore, the aim of our study was to evaluate the impact of uric acid levels on platelet function in patients treated with dual antiplatelet therapy (DAPT) with clopidogrel or ticagrelor. Methods and results: We scheduled for platelet function assessment at 30-90 days post-discharge patients treated with DAPT (ASA + clopidogrel or ticagrelor) for an ACS or elective percutaneous coronary intervention (PCI). Platelet function was assessed by whole blood impedance aggregometry (Multiplate(®)-Roche Diagnostics AG), HRPR was considered for ASPI test >862 AU(∗)min (for ASA) and ADP test values ≥417 AU(∗)min (for ADP-antagonists). Results: We included a total of 493 patients (262 were on ASA and clopidogrel and 231 on ASA and ticagrelor). Patients were divided according to quartiles of serum uric acid levels measured at the time of platelet aggregation assessment (Group 1 <4.6 mg/dL, n = 114; Group 2, 4.7-5.8 mg/dL, n = 133; Group 3, 5.9-6.8 mg/dL, n = 124; Group 4, >6.9, n = 122). Patients with higher uric acid levels were older, more often smokers, with history of hypertension and previous coronary artery bypass surgery and renal failure and were more often on therapy with diuretics at admission. Patients with higher SUA had higher triglycerides and fibrinogen. Uric acid levels did not influence ASPI, COL, TRAP and ADP tests. High residual platelet reactivity (HRPR) was observed in 1.5% of patients treated with ASA, with no difference according to SUA quartiles (p = 0.60), confirmed at multivariate analysis after correction for baseline confounders (adjusted OR[95%CI] = 1.05 [0.44-2.52], p = 0.90). HRPR for ADP-antagonists was observed in 23.6% of patients, with no difference according to SUA quartiles (p = 0.47); this result was confirmed also after correction for baseline confounders (adjusted OR[95%CI] = 1.04 [0.84-1.28], p = 0.73). Moreover, no association was found between HRPR and uric acid levels both among patients treated with clopidogrel (p = 0.35) or ticagrelor (p = 0.74), that was confirmed after correction for baseline confounding factors (adjusted OR[95%CI] = 1.18 [0.90-1.55], p = 0.23) and (adjusted OR[95%CI] = 0.96 [0.63-1.47], p = 0.85). The absence of association between SUA and platelet reactivity was confirmed at linear regression analysis both with clopidogrel (r = 0.03, p = 0.55) or ticagrelor (r = -0.01, p = 0.85). Conclusion: This is the first large study showing that in patients receiving DAPT, uric acid levels do not influence response to ticagrelor and clopidogrel or the effectiveness of ASA.
    No preview · Article · Jan 2016 · Nutrition, metabolism, and cardiovascular diseases: NMCD
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    ABSTRACT: Residual high-on treatment platelet reactivity (HRPR) still represents a challenging matter in patients with coronary artery disease. Drug-to-drug interaction has been suggested between some statin and antiplatelet agents, despite their co-administration is mandatory in patients after an acute cardiovascular event or coronary stenting. Therefore, the aim of the current study was to investigate any impact of rosuvastatin or atorvastatin co-administration on platelet reactivity in patients receiving dual antiplatelet therapy (DAPT).
    No preview · Article · Nov 2015 · Atherosclerosis
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    ABSTRACT: Background: Aim of present study was to evaluate the impact of age on platelet function and the occurrence of high- residual on treatment platelet reactivity (HRPR) in patients treated with dual antiplatelet therapy (DAPT) with ASA and clopidogrel or ticagrelor. Methods: Patients treated with DAPT (ASA and clopidogrel or ticagrelor) were scheduled for platelet function assessment at 30-90 days post-discharge. By whole blood impedance aggregometry, HRPR was considered for ASPI test >862 AU*min (for ASA) and ADP test values >417 AU*min (for ADP-antagonists). Elderly were defined for age ≥ 70 years old. Results: Among 494 patients on DAPT, 224 (45.3%) were ≥70 years old. ADP-mediated platelet aggregation increased with decades of age (279.3±148.6 vs 319.6±171.1 vs 347.3±190.1 vs 345.7±169.2), while no difference was observed for ASA response. A reduced effectiveness of ADP-antagonists was observed among the elderly, in fact, among the 117 patients displaying HRPR (23.7%), a higher prevalence was observed among patients above 70 years old (30.4%vs 18.1%, adjusted OR[95%CI]=2.19[1.29-3.71]). Similar results were obtained among the 266 clopidogrel treated patients (38.5% vs 27.9%, adjusted OR[95%CI]= 2.91[1.46-5.8]) and in the 228 patients receiving ticagrelor (19.1%vs 8.1%, adjusted OR[95%CI]=2.55[1.02-8.59]). Conclusion: In patients receiving dual antiplatelet therapy, advanced age is independently associated with a reduced effectiveness of ADP-antagonists and a higher rate of HRPR with both clopidogrel and ticagrelor. This article is protected by copyright. All rights reserved.
    No preview · Article · Oct 2015 · Journal of Thrombosis and Haemostasis
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    ABSTRACT: Background: 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. Methods: 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. Results: 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). Conclusion: 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.
    No preview · Article · Oct 2015 · Cardiovascular Drugs and Therapy
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    ABSTRACT: Residual high-on treatment platelet reactivity (HRPR) has been associated with a 2-9 fold increased risk of acute ischemic events in patients with acute coronary syndromes or coronary stenting. However, the mechanism of suboptimal platelet inhibition are still poorly understood. Aim of present study was to evaluate the role of the percentage of reticulated platelets on HRPR with ticagrelor. In patients treated with ASA (100-160 mg) and ticagrelor (90 mg twice a day) platelet reactivity and the reticulated platelets fraction (immature platelets fraction, IPF) were assessed at 30-90 days after acute coronary syndrome. Aggregation was assessed by multiple-electrode aggregometry. HRPR was defined as ADP test >417 AU*min. Our population is represented by 190 patients, divided according to tertiles values of IPF (<2.5; 2.5-3.99; ≥4 %). Higher IPF was associated to a larger platelet volume and lower platelets count (p < 0.001), and inversely related with a history of previous coronary revascularization (p = 0.03). Twenty-one out of 190 (11.0 %) patients displayed HRPR. No difference in the levels of circulating IPF was found in patients with or without HRPR (p = 0.25), with no correlation between the rate of reticulated platelets and platelet reactivity at ADP test (r = -0.084, p = 0.26). In fact no association was observed between high levels of IPF and the occurrence of HRPR (adjusted OR[95 % CI] = 0.69[0.34-1,37], p = 0.28), even after correction for baseline differences. In patients treated with ticagrelor, the levels of circulating reticulated platelets assessed at 30-90 days post-ACS are not associated with platelet reactivity or the occurrence of HRPR.
    No preview · Article · Sep 2015 · Journal of Thrombosis and Thrombolysis
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    ABSTRACT: High on-treatment platelet reactivity (HRPR) is associated with a two- to ninefold increased risk of recurrent ischemic events among patients receiving dual antiplatelet therapy (DAPT) for coronary artery disease. However, its determinants are still poorly understood. The aim of the present study was to assess the impact of mean platelet volume (MPV) on platelet reactivity in patients receiving DAPT after an acute coronary syndrome or PCI. Patients treated with DAPT (acetylsalicylic acid [ASA] and clopidogrel or ticagrelor) were scheduled for platelet function assessment at 30 - 90 days post-discharge. By whole blood impedance aggregometry, HRPR was considered for ASPI test > 862 aggregation units (AU)*min (for ASA) and ADP test values ≥ 417 AU*min (for ADP-antagonists). Our population is represented by a total of 487 patients on DAPT, divided according to MPV tertiles (< 10.4 fl; 10.4 - 11.29 fl; ≥ 11.3 fl). Larger-sized platelets were associated with use of statins (p < 0.001) and beta-blockers (p = 0.03), higher hemoglobin levels (p = 0.002) and lower platelets count (p < 0.001). Higher platelet reactivity was observed at ASPI test in patients with higher MPV (r = 0.12, p = 0.008), but not for ADP-mediated aggregation (r = -0.007, p = 0.88). However, a low prevalence of HRPR was observed with ASA, with no impact of MPV tertiles (1.2 vs 1.1 vs 1.6%, p = 0.70, adjusted OR [95% CI] = 1.05 [0.51 - 1.77], p = 0.87). MPV did not influence the prevalence of HRPR for ADP-antagonists (25.9 vs 1 vs 26.5%, p = 0.89; adjusted OR [95% CI] = 1.1 [0.84 - 1.45], p = 0.50) with similar results among the 259 patients receiving clopidogrel (adjusted OR [95% CI] = 1.15 [0.82 - 1.62], p = 0.43) and the 228 patients on ticagrelor (adjusted OR [95% CI] = 1.46 [0.84 - 2.55], p = 0.18). In patients receiving DAPT, MPV does not affect the response to major antiplatelet therapies. In fact, MPV elevation does not influence the risk of HRPR with clopidogrel, ticagrelor or ASA.
    No preview · Article · Jun 2015 · Expert Opinion on Pharmacotherapy
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    ABSTRACT: Dual antiplatelet therapy (DAPT) is considered essential in clinical management of patients undergoing percutaneous coronary revascularization (PCI) or Acute Coronary Syndromes (ACS). However, the optimal platelet inhibition is not always obtained, with high residual platelet reactivity (HRPR) increasing stent thrombosis and recurrent ischemic events. Aim of the present study was to investigate the impact of body mass index (BMI) on platelet reactivity in patients on DAPT. We included patients treated with ASA (100-160 mg) and clopidogrel (75 mg) or ticagrelor (90 mg twice a day) for ACS or Drug-Eluting Stent (DES) implantation. Platelet reactivity was assessed at 30-90 days post-discharge by multiple-electrode aggregometry. HRPR for ADP-antagonists was defined as ADP-test results >417 AU*min. HRPR for ASA was considered for ASPI-test >862 AU*min. Our population is represented by 498 patients, 308 (61.8%) were treated with clopidogrel and 190 (38.2%) with ticagrelor. Overall, higher BMI was related with younger age (p=0.003), higher prevalence of diabetes mellitus (p<0.001), hypercholesterolemia (p=0.017), hypertension (p<0.001), chronic therapy with ARB (p=0.019), CCB (p=0.003). Higher values of BMI directly related with haemoglobin (p=0.02), triglycerides (p<0.001), glycaemia (p=0.035), HbA1c (p<0.001), and inversely related with HDL cholesterol (p=0.01). BMI did not influence the effectiveness of ASA, while it was associated to a non significant trend for higher platelet reactivity (r=0.08, p=0.08) for ADP-antagonists. In fact, 111 patients (22.3%) displayed HRPR at ADP test (> 417 AU*min), with no statistically significant difference according to BMI (20.3% vs 27.1% vs 25.7%, p=0.28; adjusted OR[95%CI]= 1.19[0.86-1.64], p=0.30). However, results were different when considering separately patients receiving clopidogrel or ticagrelor.In the clopidogrel-treated subgroup significantly higher ADP-mediated aggregation values were found in patients with higher BMI (r=0.14, p=0.023), that emerged as an independent predictor of HRPR with clopidogrel (OR[95%CI]= 1.45 [1.01-2.12], p=0.049).On the contrary, no impact of BMI was observed in the ticagrelor-treated subgroup for platelet reactivity (r=-0.036, p=0.62) or the prevalence of HRPR (adjusted OR[95%CI]= 0.73[0.39-1.36], p=0.32). Present study shows that among patients treated with DAPT for coronary artery disease, higher BMI is related to an increased platelet reactivity and a higher prevalence of HRPR in clopidogrel treated patients, while not significantly influencing the effectiveness of ticagrelor or ASA.
    No preview · Article · Jun 2015 · Journal of cardiovascular pharmacology
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    ABSTRACT: Cardiovascular disease is the leading cause of morbidity and mortality in hemodialysis patients; the increased risk of cardiovascular disease is due to accelerated atherosclerosis, inflammation and impaired lipoprotein metabolism. We aimed to evaluate lipoprotein-associated phospholipase A2 (Lp-PLA2) and some pro-inflammatory aspects of the lipoprotein profile in dialyzed patients in order to evaluate the relationship with the accelerated atherosclerosis and vascular accidents. In 102 dialysis patients and 40 non-uremic controls, we investigated the lipoprotein plasma profile, high sensitivity C-reactive protein (CRP), ceruloplasmin and serum amyloid A protein (SAA), and followed patients for 1 year to analyze the risk of acute cardiovascular events. Total cholesterol, low-density lipoprotein and high-density lipoprotein plasma levels were significantly lower in uremic patients than controls, whereas CRP, SAA, ceruloplasmin, Lp-PLA2 and their ratio with apolipoprotein A1 were significantly higher. Patients with Lp-PLA2 levels >194 nmol/min/ml had more acute cardiovascular events than patients with lower values. Our results show that in dialysis subjects: (1) low-density lipoproteins show a more atherogenic phenotype than in the general population; (2) high-density lipoproteins are less anti-inflammatory; (3) Lp-PLA2 could potentially be used to evaluate cardiovascular risk.
    No preview · Article · May 2015 · Journal of nephrology
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    ABSTRACT: Residual high-on treatment platelet reactivity (HRPR) predicts outcomes and major cardiovascular events. Ticagrelor has provided pharmacological and clinical evidence of more predictable and more potent antiplatelet effect as compared to clopidogrel. However, so far, few data have investigated the prevalence and predictors of HRPR in unselected patients treated with ticagrelor, that is therefore the aim of the current study. Our population is represented by 195 patients undergoing coronary stenting for ACS and receiving ASA and ticagrelor. Platelet function was assessed by Multiplate impedance aggregometry (MEA) between 1 and 3months after stenting. Main clinical features and biochemistry parameters were collected. HRPR for ticagrelor was defined for aggregation>417 AUC after MEA-ADP stimulation. A total of 26 patients, (13.3%), displayed HRPR with ticagrelor. Older age (≥70years, p=0.002), hypertension (p=0.02) previous myocardial infarction (p=0.04), therapy with nitrates and beta-blockers (p=0.02), diuretics (p=0.03) and fasting glycaemia (p=0.05) were associated to HRPR with ticagrelor. By multivariate analysis, age≥70years (OR [95%CI]=4.6[1.55-13.8], p=0.006), concomitant therapy with beta-blockers (OR [95%CI]=3.2[1.06-9.6], p=0.04) and platelets count (OR[95%CI]=1.0007 [1-1.016], p=0.05) were identified as independent predictors of HRPR with ticagrelor. The present study firstly demonstrates that the occurrence of HRPR in patients treated with ticagrelor is not so futile, as it was observed in 13% of patients treated with ticagrelor. Older age, beta-blockers administration and platelets count are independent predictors of HRPR with ticagrelor. Copyright © 2015. Published by Elsevier Inc.
    No preview · Article · May 2015 · Vascular Pharmacology
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    ABSTRACT: Suboptimal platelet inhibition with antiplatelet treatments is associated with a severe prognosis in patients with coronary artery disease and the identification of its determinants is still challenging. Homocysteine elevation has emerged as a pro-thrombotic factor, influencing coagulative status, endothelial function and potentially modulating platelet aggregation. We therefore aimed to evaluate the effects of homocysteine (Hcy) levels on platelet reactivity in patients receiving acetylsalicylic acid (ASA) with or without ADP-antagonists. Patients undergoing coronary angiography and receiving ASA (100 to 160 mg/daily) for > 7 days, with or without ADP-antagonists, were included. Aggregation tests were performed by Multiple Electrode Aggregometry (MEA). Suboptimal platelet inhibition was defined as on-treatment aggregation above the lower limit of normality. Our population is represented by 508 ASA treated patients, 406 (80.1%) of whom on dual antiplatelet therapy (ASA and ADP-antagonists). Hcy levels above the median (15.1 nmol/ml) were associated with male gender (p=0.04), hypertension (p=0.004), hypercholesterolemia (p=0.03), ageing, renal failure (<0.001, respectively), previous coronary bypass grafting (p=0.04), therapy with calcium antagonists (p=0.04) and diuretics (p=0.001), multivessel coronary artery disease (p=0.03). Higher Hcy directly related with serum creatinine and uric acid (p<0.001).Suboptimal platelet inhibition was found in 16 patients (3.2%) for ASA and for ADP-antagonists in 80 patients (19.7%).Hcy levels significantly affected suboptimal response to ASA, but not to ADP-mediated aggregation. In fact, a linear relationship was found between homocysteine and platelet reactivity after stimulation with arachidonic acid (r=0.14, p=0.004), collagen (r=0.12, p=0.02), but not with ADP (r=0.02, p=0.77).Moreover, after correction for baseline differences, Hcy above the median was confirmed as an independent predictor of impaired ASA response (adjusted OR[95%CI]=3.7[1.08-12.4], p=0.04). Among patients with coronary artery disease, elevated homocysteine is an independent predictor of suboptimal response to ASA, but not to ADP-antagonists.
    No preview · Article · Feb 2015 · Journal of Cardiovascular Pharmacology
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    ABSTRACT: Aims: To evaluate the prognostic implications of baseline cardiac troponin (cTn) values in the normal range in stable coronary artery disease (CAD) patients successfully treated with percutaneous coronary intervention (PCI). Methods and results: We investigated the correlation between pre-procedural cTnI levels and major clinical adverse events at three years of follow-up in 1,063 consecutive stable CAD patients with normal baseline cTnI levels, successfully treated with PCI. Patients with pre-procedural cTnI levels in the upper tertile showed an increased long-term risk of overall death (HR 3.17, 95% CI: 1.62 to 6.21; p=0.0001), cardiac death (HR 5.09, 95% CI: 2.30 to 11.25; p=0.002), myocardial infarction (MI) (HR 2.34, 95% CI: 1.45 to 3.76; p=0.003) and target vessel failure (TVF) (HR 1.91, 95% CI: 1.28 to 2.84; p=0.006). Pre-procedural cTnI levels remained significantly correlated after adjustment for clinical and angiographic findings. Analysis of pre-PCI values eliminated any association of post-PCI values with prognosis. Conclusions: In stable CAD patients successfully treated with PCI, pre-procedural cTnI levels, in the upper limits of the normal range, are associated with hard cardiac endpoints.
    No preview · Article · Nov 2014
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    ABSTRACT: Background Intracoronary Abciximab administration during primary percutaneous coronary intervention (pPCI) could offer theoretical advantages over the intravenous route. Besides antiplatelet effects, Abciximab can modulate inflammation via cross-reactivity with GPIIb/IIIa, avb3, and aMb2 receptors. The aim of our study was to assess whether the Abciximab administration route could influence its anti-inflammatory effects.Methods Eighty-nine consecutive ST elevation myocardial infarction patient candidates for pPCI were randomized to intracoronary (Group A-47 patients) or intravenous (Group B-42 patients) Abciximab bolus administration. The primary endpoint was the extent of inflammation, measured by C-reactive protein (CRP), vascular cell adhesion molecule 1 (VCAM-1) and inter-cellular adhesion molecule 1 (ICAM-1) levels. This study is registered with, NCT01757457.ResultsData are expressed in medians (interquartiles). In both groups, troponin levels were similar [baseline: 0.12 (0.03-0.94) vs. 0.27 (0.07-1.24) ng/ml, P=0.73; postprocedural: 22.00 (14.75-69.43) vs. 31.96 (8.23-7.20) ng/ml, P=0.83]. Both groups also showed similar baseline [0.31 (0.14-0.69) vs. 0.22 (0.09-0.59) mg/ml, P=0.80] and postprocedural CRP levels [2.28 (1.37-4.23) vs. 2.16 (1.15-3.22) mg/dl, P=0.69], similar baseline [272.5 (224.7-340.8) vs. 262.2 (221.2-306.4) ng/ml, P=0.33] and postprocedural soluble ICAM-1 levels [281.5 (244.6-337.4) vs. 287.2 (226.9-359.2) ng/ml P=0.71], and similar baseline [771.6 (620.9-971.0) vs. 748.6 (592.2-838.8) ng/ml, P=0.30] and postprocedural soluble VCAM-1 levels [785.2 (671.6-947.1) vs. 745.9 (641.1-841.9) ng/ml, P=0.17]. In-hospital and 6-month event rates were similar in the two groups.Conclusions Our study suggests that Abciximab has similar anti-inflammatory effects irrespective of the administration route. It is unlikely that the potential clinical benefits of intracoronary Abciximab can be related to modulation of integrin receptors.
    Full-text · Article · Jul 2014 · Journal of Cardiovascular Medicine
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    ABSTRACT: Background: In previous studies elevated Asymmetric NG, NG - dimethylarginine (ADMA) plasma levels, an endogenous nitric oxide synthase inhibitor, correlated with the severity of hepatic venous pressure gradient measurement, both in peripheral and in hepatic veins. The aim of this study was to explore whether elevated ADMA plasma levels were able to predict the presence of esophageal varices (EV) and/or large EV in patients with cirrhosis. Methods: 74 cirrhotic patients who had undergone elective upper gastrointestinal endoscopy in order to assess the presence of portal hypertension and predictors of EV and/or large EV. ADMA levels were assayed by an ELISA test (Immundiagnostik AG, Germany). Results: 53 patients had EV (26/53 had large EV). Univariate analysis of low hemoglobin (p = 0.045), PT-INR (p = 0.003), albumin (p = 0.024), bilirubin (p = 0.036), Child-Pugh score (p = 0.026), and ascites (p = 0.036) predicted the presence of EV. Multivariate analysis predicted EV for only PT-INR. The presence of large EV was predicted with univariate analysis of ADMA plasma levels (p = 0.013), low hemoglobin (p < 0.001), PT-INR (p = 0.001), albumin (p = 0.001), bilirubin (p = 0.026), Child-Pugh score (p < 0.001), ascites (p = 0.004). Sensitivity, specificity, predictive positive and negative values of ADMA plasma level > 0.5 micromol/L(-1) in predicting large EV were 0.69 (95% CI 0.53 - 0.82), 0.51 (95% CI 0.40 - 0.62), 0.43 (95% CI 0.31 - 0.56), 0.76 (95% CI 0.62 - 0.86), while the area under the ROC curve was 0.65 (95% CI 0.51 - 0.79). Conclusions: ADMA plasma levels were increased in cirrhotics with more advanced liver failure but did not prove to be a useful clinical tool for predicting the presence of esophageal varices or large esophageal varices.
    No preview · Article · May 2014 · Clinical laboratory
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    ABSTRACT: Venlafaxine (V) is a serotonin-norepinephrine selective reuptake inhibitor, mainly metabolized by cytochrome P4502D6 (CYP2D6). CYP2D6 polymorphisms result in a variety of phenotypes: poor (PMs), intermediate (IMs), extensive (EMs), and ultrarapid metabolizers (UMs). PMs usually show poor tolerance to drugs metabolized by CYP2D6, while UMs need greater doses. The aim of this study was to evaluate the impact of CYP2D6 genotype on V dosage, therapeutic response, and side effects in a clinical outpatient setting. 47 patients with Major Depressive Disorder, treated with V 75 - 300 mg/day, underwent CYP2D6 genotyping using the INFINITI-CYP2D6 assay. Duration of treatment and clinical outcome (Clinical Global Impression [CGI] effectiveness index) were assessed. CGI assessment was performed after 6 weeks, 6 months, and 1 year of treatment with a V median dose of 150 mg/day. CYP2D6 genotyping resulted in 1 PM, 3 IMs, 42 EMs, and 1 UM. The UM took the greatest V dose (375 mg) without side effects; IMs/PMs took moderate/high doses of V (150 - 300 mg) without adverse effects; EMs displayed high response variability. PM/IM patients responded to V differently than expected according to genotype. However, the UM patient responded to a dosage higher than the usual therapeutic range and without developing side effects, suggesting an association between CYP2D6 gene duplication and the therapeutic efficacy of venlafaxine. The CYP2D6 genotyping may thus provide clinicians with a potential explanation for those patients requiring greater doses of CYP2D6 substrates in order to obtain the same therapeutic efficacy.
    No preview · Article · Mar 2014 · Clinical laboratory
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    ABSTRACT: Background: The identification of prothrombin G20210A polymorphism (PT20210) is normally included in the thrombophilia laboratory panel and evaluated by DNA-based molecular analysis. To date, a routine coagulation test that helps to identify PT20210 carriers has not been set, in contrast to the FV Leiden mutation, for which a functional coagulation test, the Activated Protein C Resistance test (APCR), is available as a screening tool. Moreover the molecular tests are expensive and are used inappropriately. The aim of the study is to characterize the effects of the prothrombin G20210A mutation on routine clotting assays in order to identify, if any, coagulation tests that can be used as a first-line cost-effective assay for prothrombin G20210A polymorphism.
    No preview · Article · Jan 2014 · Clinical laboratory
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    ABSTRACT: Inherited hemoglobin disorders (sickle-cell disorders and thalassaemias) represent an increasing global health problem. The early detection of sickle cell disease allows counselling for family members about disease management and future reproductive decisions. The aim of the present study was to estimate the birth prevalence of hemoglobinopathies in newborns of Italian couples and couples of immigrants from endemic areas living in an urban area of northern Italy in order to assess the opportunity of implementing a neonatal screening programme for hemoglobin disorders. Inclusion criteria were infants with at least one of the parents from high risk areas of hemoglobinopathies (Po delta and Sardinia, Italy; Mediterranean area; sub-Saharan Africa; Brazil; Asia) or a positive family history for hemoglobinopathies. The number of infants included in the present study was 337: 13.8% out of 2447 children born at Azienda Ospedaliera Universitaria (AOU) "Maggiore della Carità", Novara, Italy, from 31 December 2012 to 31 January 2014 and 47.6% of 710 infants with at least one foreign parent. 232 infants were wild-type (68.8%) for hemoglobin variants; 48 subjects (14.2%) had no hemoglobin variants, but we could not exclude the presence of a thalassemia trait (Hb A < 15%): a further monitoring of hemoglobin electrophoresis at 6 months was therefore recommended. 20 infants (5.9%) had Hb S (7.7% ± 3 of the total hemoglobin; range 3.5 - 13) and were diagnosed as Hb S carriers and 2 infants (0.6%) had Hb C (7.8% and 12.1% of the total hemoglobin, respectively) and were diagnosed as Hb C carriers. Based on our results, we can conclude that: (i) the sickle-cell disorder (Hb S) is relatively high in our territory, with a heterozygous frequency in infants at risk of 5.9%; (ii) the neonatal screening for hemoglobin disorders appears to be a valid, easy to perform test, which allows an early diagnosis and timely payment of hemoglobinopathies in populations at risk.
    No preview · Article · Jan 2014 · Clinical laboratory
  • Roberta Rolla · Giorgio Bellomo

    No preview · Article · Nov 2013 · Clinical laboratory
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    ABSTRACT: Glycoprotein IIb-IIIa (Gp IIb-IIIa), a fibrinogen receptor located on platelet surface, is a key point in the pathway leading to platelet aggregation. Therefore, great interest has emerged in the last decades on its pharmacological block, both by irreversible binding of abciximab or by competitive small molecules (tirofiban and eptifibatide). Gp IIb-IIIa inhibitors, in fact have demonstrated to provide benefits in clinical outcome among patients with acute myocardial infarction and in complex elective percutaneous coronary intervention (PCI) procedures. Still unclear is whether the genetic Leu 33Pro substitution in Gp IIIa may affect the extent of platelet aggregation inhibition by these drugs. Therefore, the aim was to evaluate whether this polymorphism (PlA) may influence inhibition of platelet aggregation after Gp IIb-IIIa administration in patients undergoing coronary angioplasty. We analyzed 80 patients undergoing nonurgent coronary revascularization and receiving Gp IIb-IIIa inhibitors (bolus and endovenous infusion; 40 patients with Abciximab and 40 patients with eptifibatide or tirofiban). The aggregation tests were performed at baseline and after 10 min, 1 h and 4 h, through multiplate impedance aggregometry. The PlA polymorphic variant was found in 26 patients (32.5%). The PlA carriers did not differ significantly from wild-type subjects for main clinical and angiographic features, except for in-stent restenosis that was more frequent among PlA carriers (P = 0.003). Therapy and aggregation values at baseline were similar in the two groups. The Leu33Pro substitution did not influence platelet response after Gp IIb-IIIa administration, which was confirmed for both abciximab and small molecules. This study showed that Leu33Pro polymorphism of Gp IIIa does not affect the extent of inhibition of platelet aggregation by Gp IIb-IIIa inhibitors.
    No preview · Article · Feb 2013 · Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis
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    ABSTRACT: The increasing demand for therapeutic monitoring in patients receiving antiplatelet therapy has been paralleled by the development of instruments and tests whose clinical usefulness is still under debate. We devised a laboratory approach to detect patients with antiplatelet resistance at risk to develop thrombotic events. One hundred and eighty patients, under aspirin and clopidogrel after angioplasty and stent implantation, were studied by PFA100(®) with collagen/epinephrine (CoEPI, cutoff 165s) cartridge and by Multiplate(®) using arachidonic acid (ASPItest, pos < 862AUC), ADP (ADPtest, pos < 417AUC), and collagen (COLtest, pos < 607AUC). Only 67 of 173 patients with ASPI < 862 displayed a prolonged CoEPI and up to 65 patients had normal CoEPI despite ASPI < 300. Patients with ASPI < 300 had significantly lower COL than patients with ASPI > 300. One hundred and thirty-eight patients displaying ADP < 417 had significantly lower COL than those with ADP > 417. Association between COL and ADP remained after ASPI stratification: in patients with suboptimal (ASPI 300-892) or maximal (ASPI < 300) response to aspirin, having ADP < 417 (clopidogrel responsive) increased COL positivity, respectively, from 9.5 to 58.8% and from 47.6 to 82.7%. A combination of specific tests may be useful in identifying higher-risk patients with poor compliance or drug resistance who potentially may benefit from therapy change.
    No preview · Article · May 2012 · International journal of laboratory hematology
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    ABSTRACT: The oral glucose tolerance test (OGTT) is widely employed to evaluate insulin resistance in children with growth hormone deficiency. Due to the difficulty in blood sampling, hemolysis is a frequent pre-analytic interference. The present study was performed to characterize the effects of hemolysis on insulin assays, in order to assess the need to generate automatic hemolysis reports and/or to reject hemolyzed samples. Insulin plasma levels were measured using a Siemens ADVIA Centaur on samples obtained from children with suspected GH deficiency at risk for insulin resistance during OGTT. The presence of hemolysis (with a concentration of free hemoglobin above 75 mg/dL) promotes a dose- and time-dependent decrease in immunoreactive insulin at any time-point evaluated during OGTT. As a consequence, the variability of insulin is particularly high (often exceeding 100% of the mean value) as compared to that of glucose. This variability is markedly reduced after removal of the hemolyzed samples. When hemolysis is not taken into account a misinterpretation of insulin secretion pattern can occur. It is therefore imperative to: (i) analyze blood samples immediately after sampling, (ii) reject samples with a concentration of free hemoglobin equal to or above 125 mg/dL and (iii) always report the possible interference.
    No preview · Article · Jan 2012 · Clinical laboratory

Publication Stats

565 Citations
227.60 Total Impact Points


  • 2010-2015
    • Azienda Ospedaliero Universitaria Maggiore della Carità
      • Department of Cardiology 2
      Novara, Piedmont, Italy
  • 2003-2015
    • Amedeo Avogadro University of Eastern Piedmont
      • Interdisciplinary Research Center of Autoimmune Diseases IRCAD
      Novara, Piedmont, Italy
  • 2001
    • Newcastle University
      Newcastle-on-Tyne, England, United Kingdom