Maria Serena Parri

Monitoring of monocyte functional state after extracorporeal circulation: a flow cytometry study.

Cardiovascular surgery with cardiopulmonary bypass (CPB) induces systemic inflammation and postoperative complications depending on pro‐ and anti‐inflammatory mechanisms. Activated polymorphonuclear cells and monocytes may be responsible for morbidity associated with CPB. Knowledge of the monocyte functional state in particular may help to develop protective interventions.

Reference intervals for brain natriuretic peptide in healthy newborns and infants measured with an automated immunoassay platform

Abstract Background: In order to assess the reference intervals for B-type natriuretic hormone (BNP) in the first days of life, we measured peptide concentrations using the fully automated Access platform. Methods: Plasma BNP was measured in 188 apparently healthy newborns and infants throughout the first month of extra-uterine life, as well as in 245 healthy infants ranging from 1 month to 12 years of age. Results: BNP showed the highest concentrations in the first 2 days of life, with a progressive decline afterwards. Moreover, BNP values in the first week of life were significantly higher (p<0.0001) than values observed in the next periods. As a result, a significant negative correlation was found between BNP and age values when considering all 433 samples (ρ=–0.816, p<0.0001 by the Spearman rank correlation test). There was no significant difference between BNP values found in males and females. Conclusions: According to this data, our study indicates that at least two reference intervals should be used for newborns and infants. The first, with higher BNP values for neonates in the first week of extra-uterine life, and the other, with lower BNP values for infants aged 2 weeks to 12 years. Clin Chem Lab Med 2010;48:697–700.

Pantoprazole significantly interferes with antiplatelet effect of clopidogrel: Results of a pilot randomized trial

BACKGROUND The CYP2C19*2 polymorphism is significantly associated with residual platelet reactivity (RPR) and maybe a major confounding factor in studies evaluating pharmacological interactions with clopidogrel. OBJECTIVES We sought to evaluate the influence of a proton pump inhibitor (PPI), pantoprazole, indicated as relatively less influent than other PPIs, on the antiplatelet effect of clopidogrel, considering a stratification of the population for the presence of cytochrome 2C19*2 polymorphism. METHODS 105 patients with ST elevation myocardial infarction (STEMI), treated with percutaneous coronary angioplasty (PCI) and who received dual antiplatelet therapy, were randomized between pantoprazole (n=54) or ranitidine (n=51). RPR was evaluated by Platelet Function Analyzer-100 (PFA-100) with collagen-epinephrine (CEPI) and collagene-ADP (CADP) cartridges and by light transmitted aggregometry with 10 μM adenosin diphosphate (ADP) and 1mM arachidonic acid (AA), on 5 (T0) and 30 (T1) days after PCI. RESULTS Demographic, clinical and procedural data and the prevalence of CYP2C19*2 polymorphism were similar between the two groups. Not statistically differences were observed for CEPI-CT and for the maximal aggregation (MA) values with AA stimulus at both times. We observed a significant increase in MA values with ADP in PPI group at T0 (p=0.01) and T1 (p=0.03). At the multiple regression analysis PPI use remained significantly associated with ADP-MA both at T0 (p=0.05) and T1 (p=0.03). CONCLUSIONS This is the first documentation in a randomized trial, after correction for the bias of CYP2C19*2 polymorphism, that pantoprazole increases the ADP-MA in patients treated with dual antiplatelet therapy.

Reference values for plasma B-type natriuretic peptide in the first days of life.

The clinical relevance of B-type natriuretic peptide (BNP)1 and the amino terminal fragment of its prohormone (NT-proBNP) as biomarkers in pediatric heart disease have recently been shown (1)(2). BNP and NT-proBNP concentrations are dependent on age and sex, at least in adults(3). Because commercial methods are affected differently by the presence in plasma of several peptides derived from the degradation of intact prohormone and BNP(3), little if any agreement exists among reported reference intervals, especially those used for infants during the first days of extrauterine life(1). Data are scarce regarding the reference values for BNP and NT-proBNP in infancy (1)(2)(4). Recently, Nir et al.(2) summarized NT-proBNP concentrations measured with an electrochemiluminescence immunoassay method in 690 healthy individuals (47% males) with ages ranging from birth to 18 years, including 127 newborns in the first week of life (43 in the first 2 days). The NT-proBNP concentrations were highest in the first days of life, and then showed a marked decline. Concentrations in males and females differed only for children age 10–14 years. Large reference value studies for BNP for newborns and infants have …

Evaluation of platelet count after isolated biological aortic valve replacement with Freedom Solo bioprosthesis

OBJECTIVE The risk of thrombocytopenia in patients undergoing aortic valve replacement (AVR) with the Freedom Solo (FS) bioprosthesis is controversial. The aim of our study was to evaluate the postoperative evolution of platelet count and function after AVR in patients undergoing isolated biological AVR with FS. METHODS Between May 2005 and June 2010, 322 patients underwent isolated biological AVR. Of these, 116 patients received FS and were compared with 206 patients who received biological valves. Platelet count, mean platelet volume (MPV), and platelet distribution width (PDW) were evaluated at baseline (T0), first (T1), second (T2), and fifth (T3) postoperative days, respectively. RESULTS Overall in-hospital mortality was 1.5% with no difference between the two groups. Thirty-seven (11.5%) patients developed thrombocytopenia. FS implantation was associated with a higher incidence of thrombocytopenia compared with the control group (24.1% vs 4.4%, p<0.0001). Patients in the FS group showed a lower platelet count than the control group at T1 (99.4±38×10(3) μl(-1) vs 122.5±41.6×10(3) μl(-1), p<0.001), T2 (79.7±36.3×10(3) μl(-1) vs 122.5±43.3×10(3) μl(-1), p<0.001) and T3 (86.6±57.4×10(3) μl(-1) vs 158.4±55.8×10(3) μl(-1), p<0.001). Moreover, the FS group also had a higher MPV (11.6±0.9 fl vs 11±1 fl, p<0.001) and higher PDW (15.1±2.3 fl vs 13.9±2.1 fl, p<0.001) at T3. In a multivariable analysis, FS (p<0.0001), body surface area (p<0.0001), cardiopulmonary bypass time (p=0.003), and lower preoperative platelet counts (p=0.006) were independent predictors of thrombocytopenia. CONCLUSIONS The FS valve might increase the risk of thrombocytopenia and platelet activation, in the absence of adverse clinical events. Prospective randomized studies on platelet function need to confirm our data.

Post-reperfusion changes of monocyte function in coronary blood after extracorporeal circulation.

Neutrophil and mononuclear cell functional changes represent a hallmark of inflammation during cardiopulmonary bypass and cardiovascular surgery. Knowledge of mechanisms underlying monocyte functional modulation in coronary blood may be useful to develop protective interventions that can limit ischemia/reperfusion injury.

The non-thyroidal illness syndrome after coronary artery bypass grafting: a 6-month follow-up study

Abstract The non-thyroidal illness syndrome (NTIS) is considered a transient and completely reversible phenomenon, but it has been shown that it may last for several days postoperatively after coronary artery bypass grafting (CABG) surgery. This study was undertaken to assess thyroid function 6 months after uncomplicated CABG. The thyroid profile was evaluated in 40 consecutive patients undergoing CABG preoperatively, at 0, 12, 48, and 120h postoperatively, and at 6-month follow-up. Triiodothyronine (T 3), free T 3 (FT 3), free thyroxine (FT 4) and thyroid stimulating hormone (TSH) were assayed using a microparticle enzyme immunoassay. T 4 and total serum thyroid hormone-binding capacity (T-uptake) were measured on the same samples using a fluorescence polarization immunoassay. Patients with severe systemic illness and patients treated with amiodarone were excluded. All patients were euthyroid at admission. Mean age was 67.4±9.0years. There were 31 (77.5%) men. Typical NTIS was observed in all patients, and the FT 3 concentration was still reduced by postoperative day 5 (p<0.0001). At 6-month follow-up, all patients were free from cardiac symptoms, and no new cardiac events were recorded. The thyroid profile was normal in 35 patients (87.5%). One patient (4.5%) had developed overt hypothyroidism. Two patients had isolated low T 3 and FT 3 levels with normal TSH. Two patients had moderately increased FT 3 levels with suppressed TSH. In most uncomplicated patients, thyroid function returns to normal 6months after CABG. However, we observed significant alterations of the thyroid profile in 5 out of 40 patients. Further studies are needed to define the long-term consequences of postoperative NTIS.

Evaluation of the analytical performance of the advanced method for cardiac troponin I for the AxSYM platform: comparison with the old method and the Access system

Abstract Background: The determination of cardiac troponins is routinely used for rule in/out, risk stratification, and follow-up of patients with acute coronary artery syndrome. We evaluated the analytical and clinical performance of the advanced immunoassay for troponin I (cTnI) carried out on an AxSYM platform (Abbott Diagnostic Division) and compared these characteristics to those of the previous version of this assay and to cTnI on the Access 2 immunoassay system (Beckman Coulter, Inc.). Methods: We assayed plasma samples from healthy subjects (n=66) and cardiac patients (n=132) using AxSYM Plus system assays called the old (OLD AxSYM) and advanced TnI (ADV AxSYM) methods and using an Access system. Results: An improvement in analytical sensitivity (detection limit) was observed for the advanced cTnI AxSYM compared to the previous method (0.014 vs. 0.31μg/L), while the cTnI value for the 10% CV (i.e., functional sensitivity) was 0.41μg/L for the ADV and 1.9μg/L for the OLD method. The kinetics of cTnI release was similar, as evaluated in 25 patients with typical acute myocardial infarction (AMI). A close linear relationship was found between the two methods on the AxSYM system (OLD cTnI=7.436+6.858 ADV cTnI; R=0.968, n=214) and with the Access system (OLD AxSYM=7.154+7.9 Access, R=0.876, n=158; ADV AxSYM=0.23+1.209 Access, R=0.927, n=160). However, wide bias was found between the OLD and ADV AxSYM methods (mean difference 118.4μg/L, p<0.0001), while more similar results were found between the ADV AxSYM and Access methods (mean difference 2.6μg/L, corresponding to a mean percentage difference of 17%, p<0.0001). In 106 patients with symptomatic rheumatoid arthritis with high rheumatoid factor (RF) concentration, the mean cTnI measured by the ADV AxSYM method was 0.009±0.031μg/L (range 0–0.23μg/L) with a significant correlation (R=0.316, p=0.001) between cTnI and RF values. Furthermore, in 60 of these serum samples the cTnI concentration was also measured using the Access method; significant correlation with the values found by the ADV AxSYM method was observed (R=0.468, p=0.0002). Conclusions: The present study indicates that the AxSYM Troponin-I ADV immunoassay shows improved analytical sensitivity compared to the OLD AxSYM method, as well as very similar clinical results to those determined using the Access method. Clin Chem Lab Med 2006;44:1022–9.

Granulocyte- and Monocyte-Platelet Adhesion Index in Coronary and Peripheral Blood After Extracorporeal Circulation and Reperfusion

Neutrophil‐granulocyte and mononuclear‐cell functional changes occur during cardiopulmonary bypass and cardiovascular surgery. In particular, leukocyte–platelet interaction, leading to generation of heterotypic coaggregates, represents an amplification mechanism of the local inflammatory response and tissue damage.

Von Willebrand Factor Antigen Predicts Response to Double Dose of Aspirin and Clopidogrel by PFA-100 in Patients Undergoing Primary Angioplasty for St Elevation Myocardial Infarction

Von Willebrand factor (VWF) is an emerging risk factor in acute coronary syndromes. Platelet Function Analyzer (PFA-100) with Collagen/Epinephrine (CEPI) is sensitive to functional alterations of VWF and also identifies patients with high on-treatment platelet reactivity (HPR). The objective of this study was to verify the effect of double dose (DD) of aspirin and clopidogrel on HPR detected by PFA-100 and its relation to VWF and to its regulatory metalloprotease ADAMTS-13. Between 2009 and 2011 we enrolled 116 consecutive patients with ST elevation myocardial infarction undergoing primary PCI with HPR at day 5 after PCI. Patients recruited were then randomized between a standard dose (SD, n = 58) or DD of aspirin and clopidogrel (DD, n = 58), maintained for 6 months follow-up. Blood samples for PFA-100, light transmittance aggregometry, and VWF/ADAMTS-13 analysis were collected after 5, 30, and 180 days (Times 0, 1, and 2). At Times 1 and 2 we observed a significantly higher CEPI closure times (CT) in DD as compared to SD (P < 0.001). Delta of CEPI-CT (T1 − T0) was significantly related to VWF (P < 0.001) and inversely related to ADAMTS-13 (0.01). Responders had a significantly higher level of VWF at T0. Finally, in a multivariate model analysis, VWF and ADAMTS-13 in resulted significant predictors of CEPI-CT response (P = 0.02). HRP detected by PFA-100 in acute myocardial infarction is reversible by DD of aspirin and clopidogrel; the response is predicted by basal levels of VWF and ADAMTS-13. PFA-100 may be a useful tool to risk stratification in acute coronary syndromes given its sensitivity to VWF.