Sara Maggiolo

Whole blood rotation thromboelastometry (ROTEM®) profiles in subjects with non-neoplastic portal vein thrombosis

The coagulation pattern and the determinants of portal vein thrombosis (PVT), both in patients with and without cirrhosis, are still largely unknown. The aim of this study was to evaluate whole blood thromboelastometry profile, performed by ROTEM®, of both cirrhotic and non-cirrhotic subjects with PVT. Two different groups were considered: i) 14 non-cirrhotic PVT patients, ii) 35 cirrhotic patients with PVT. Controls were sex- and age-matched healthy volunteers and cirrhotic subjects without PVT, respectively. ROTEM® assays (i.e. INTEM, EXTEM, NATEM, and FIBTEM) and traditional coagulative parameters (i.e. platelet count, PT/INR, aPTT, and fibrinogen) were performed on blood samples from each subject. There were no significant differences in ROTEM® profile, as for INTEM, EXTEM, and NATEM assays, and in traditional coagulative parameters, between PVT patients, both with and without cirrhosis, and control groups. Interestingly, Maximum Clot Firmness (MCF) in FIBTEM was significantly higher in non-cirrhotic PVT patients (19 mm) than in healthy volunteers (11 mm, p<0.05). The amplitude of MCF in FIBTEM revealed to be a useful tool to discriminate non-cirrhotic subjects with PVT from those without thrombotic events. Larger prospective studies are needed to evaluate the relevance of the association between the alterations of ROTEM® profiles and PVT in cirrhotic patients.

Hypercoagulability detected by whole blood thromboelastometry (ROTEM®) and impedance aggregometry (MULTIPLATE®) in obese patients

INTRODUCTION Obesity has been associated with hypercoagulability and to increased risk of both arterial and venous thromboembolic events. Many different and complex changes in plasma coagulation factors have been described in patients with obesity. The aim of this case-control study is to evaluate hypercoagulability in a group of overweight and obese subjects by whole blood rotation thromboelastometry (ROTEM®) and impedance aggregometry (Multiplate®). METHODS ROTEM® and Multiplate® analyses were performed in 80 subjects with a BMI ≥ 25 Kg/m(2), of whom 20 overweight [BMI = 25-29.9 Kg/m(2)], 20 with I degree obesity [BMI = 30-34.9 Kg/m(2)], 20 with II degree obesity [BMI = 35-39.9 Kg/m(2)] and 20 with III degree [BMI > 40 Kg/m(2)] and compared with 80 age and gender-matched normal weight healthy individuals. RESULTS Thromboelastometry. In INTEM and EXTEM tests MCF and AUC were significantly increased in III degree obese compared with controls. MCF in FIBTEM was significantly higher in I, II and III degree obesity than controls (p = 0.027, 0.002 and < 0.001, respectively). Impedance aggregometry. A significant difference in platelet aggregation was found between III degree obese subjects and healthy controls in each of the tests considered. A significant correlation between FIBTEM-MCF and aggregometry parameters with BMI, waist circumference, leptin levels and high sensitive-C reactive proteins was also found. CONCLUSIONS A relationship between hypercoagulability detected by whole blood thromboelastometry and aggregometry and increased fat mass is shown. Hypercoagulability also correlated with inflammatory markers. Point-of-care tests can be used to assess the degree of hypercoagulability and hyperaggregability in obese patients. Wider studies are needed to confirm our observations.

Short-term exposure to high levels of air pollution as a risk factor for acute isolated pulmonary embolism

BACKGROUND The association between air pollution exposure and occurrence of venous thromboembolism is a matter of debate. This retrospective case-control study investigated the associations between one months exposure to elevated levels of different pollutants (i.e. PM10, CO, NOx, O3, SO2, Benzene, Benzoapyrene, Nickel, Lead Arsenic) and the development of acute isolated pulmonary embolism (PE). METHODS The cases included 33 patients consecutively admitted to Padua Hospital with an objectively proven diagnosis of acute unprovoked (i.e. without predisposing conditions) isolated (i.e. without deep vein thrombosis) PE. The control group consisted of 72 consecutive patients with objectively proven acute provoked (i.e. associated to predisposing conditions) isolated PE. Average mean concentrations of pollutants in the month before PE diagnosis were computed by monitors located at 2 different sites throughout the city of Padua, and were obtained from the Regional Agency for Environmental Protection. RESULTS Individuals who had PM10, NOx, Benzene, Benzoapyrene, Cadmium, and Lead exposure equal/above the 2nd tertile, measured in controls, showed a significant increase in the risk of unprovoked PE. In case of PM10 and Benzoapyrene this risk was not affected after adjustment for possible confounders. In fact, in the multivariate logistic regression analysis, the OR values were 5.24 (95% CI: 1.52-18.12) for PM10 and 3.95 (95% CI: 1.06-14.71) for Benzoapyrene exposure in the month before PE diagnosis. CONCLUSIONS Our results, although preliminary, identify short-term (i.e. one month) exposure to elevate levels of air pollutants as a possible risk factor for the development of acute isolated PE. Larger studies are needed to confirm our results.

Thromboelastometry profiles in patients undergoing thrombolytic therapy for acute ischaemic stroke

Thromboelastometry profiles in patients undergoing thrombolytic therapy for acute ischaemic stroke -

Whole blood thromboelastometry profiles in women with preeclampsia

Abstract Background: Preeclampsia (PE) is a pregnancy complication characterized by high blood pressure and significant amounts of protein in the urine. Various coagulation abnormalities have been described in pregnant women with PE. The aim of the present case-control study was to evaluate whole blood thromboelastometry profiles, performed by ROTEM®, in women with PE in order to better characterize the PE-related discoagulopathy. Methods: Standard ROTEM® (Tem International GmbH, Munich, Germany) parameters evaluating clot initiation [clotting time (CT)], propagation [clot formation time (CFT); α-angle], stability [maximum clot firmness (MCF)] and lysis [maximum lysis (ML)] in INTEM, EXTEM, NATEM, and FIBTEM assays were performed in 30 consecutive pregnant women with PE at diagnosis. Sixty (1:2 ratio with cases) healthy pregnant women, matched for gestational age (±2 weeks) with the cases, acted as controls. Platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, antithrombin and D-Dimer were also evaluated. Results: Preeclamptic women showed a significantly more rapid propagation phase in EXTEM assay than controls (CFT 62±15 vs. 75±15 s and α-angle 78±4 vs. 75±4°, p<0.01 in both cases). Moreover, MCF was significantly higher and ML significantly lower in women with PE than in healthy pregnant women (p=0.001 for all comparisons). Conclusions: ROTEM® profiles in women with PE were characterized by an increased tissue factor driven clot propagation capability. In addition, higher clot stability due both to the increase in clot firmness and the decrease in blood fibrinolysis was observed. Larger studies are needed to identify the clinical relevance of ROTEM® alterations in women with PE.

Short-term exposure to high levels of air pollution (nickel) and the risk of acute unprovoked proximal deep vein thrombosis in the legs

We read with great interest the narrative review recently published by Mannucci et al. [1] in Intern Emerg Med journal dealing with the adverse effects on health of air pollution exposure. As clearly stated by the authors, studies published so far in literature report data mainly on particulate matter (PM), ozone, nitrogen dioxide (NO2), benzene, carbon monoxide (CO) and sulphur dioxide (SO2), but air pollution is ‘‘a mixture of thousands of components’’. In an attempt to overcome this limitation, we recently published data on the association between short-term exposure to elevated levels of air pollution, and the risk of developing a provoked or unprovoked isolated pulmonary embolism (PE) taking into account ‘‘traditional’’ and ‘‘novel’’ pollutants [2]. In this retrospective case–control study, we identified short-term (i.e. 1 month) exposure to elevated levels of PM10 and Benzoapyrene as possible risk factors for the development of acute isolated unprovoked PE. Based on these results, we performed a retrospective case– control study to evaluate the association, if any, between the short-term (i.e. 1 month and one trimester) exposure to elevate levels of air pollution, and the risk of developing an acute idiopathic proximal deep vein thrombosis (DVT) in the legs. All eligible patients enrolled were admitted between April 2010 and December 2012 to the thrombosis unit of our department with an onset of acute symptoms (B2 days) indicative of DVT in the legs, and with a Doppler ultrasound confirmed the diagnosis of proximal DVT. Participants were asked to report the presence of any transient risk factors for DVT in the month prior to the hospital (i.e. trauma, immobilization or surgery, hormonal treatment, pregnancy or puerperium, medical diseases, active cancer). Cases considered were those individuals with unprovoked (without any detectable predisposing factors for thrombosis) DVT; controls were those patients with a provoked (associated to permanent or transient risk factors) DVT. Patients under anticoagulant treatment at the time of the diagnosis of VTE, or younger than 18 or with a previous episode of PE or DVT, or who were residents outside the city of Padua were excluded. Blood samples for thrombophilia screening (i.e. antithrombin, protein C, protein S deficiencies; lupus-like anticoagulants; factor V Leiden and prothrombin gene mutation) were collected from each participant. The level of exposure for each patient enrolled in the study was assessed as previously reported [2]. In particular, average concentrations data of different pollutants (i.e. PM10, CO, NOx, O3, SO2, Benzene, Benzoapyrene, Nickel, Lead and Arsenic) measured over the month and the trimester preceding the DVT diagnosis from two monitoring sites around the city of Padua were obtained from the Regional Agency for Environmental Protection (Agenzia Regionale per la Protezione Ambientale—ARPA Veneto). During the study period, 233 subjects with a diagnosis of acute proximal DVT in the legs were evaluated. Thirteen patients were excluded: five patients from out of town; four Electronic supplementary material The online version of this article (doi:10.1007/s11739-015-1363-9) contains supplementary material, which is available to authorized users.

Predictors of postoperative bleeding in children undergoing cardiopulmonary bypass: A preliminary Italian study

BACKGROUND Several characteristics such as demographics, pre-existing conditions, surgical procedure, perioperative coagulopathy may predispose children undergoing cardiopulmonary bypass (CPB) to bleeding complications. As yet, studies on risk factors for postoperative bleeding have brought mixed results. The purpose of our study was therefore to retrospectively evaluate the parameters able to predict postoperative bleeding in a group of consecutive children undergoing cardiac surgery involving CPB. METHODS We collected demographic and perioperative laboratory data, as well as intraoperative transfusion requirements and blood loss during the first 24h after surgery in a group of consecutive children (aged ≥1month) scheduled for cardiac surgery with CPB at Padua University Hospital between June 2014 and April 2015. Cases were patients who experienced a 24-h postoperative blood loss ≥80th percentile. Univariate and multivariate logistic regression analyses were performed to determine the independent parameters associated with a high 24-h postoperative chest tube drainage volume. RESULTS Eighty-three children (M:F 38:45; age range 1-168months) were enrolled. Age<7.7months (p 0.015), postoperative platelets <109×109/L (p 0.003) and postoperative D-dimer ≥2350μg/L (p 0.007) were the variables most significantly and independently associated with excessive 24-h postoperative blood loss. CONCLUSIONS Although preliminary, our study identified younger age, lower postoperative platelet count and higher D-dimer plasma levels as possible risk factors for postoperative bleeding. As for coagulation parameters, our results suggested consumptive coagulopathy might cause a strong predisposition to postoperative bleeding in children. Large-scale prospective studies would provide insight into the early diagnosis and treatment of CPB-related coagulopathies.

On-treatment platelet reactivity in peripheral and coronary blood in patients undergoing primary PCI for ST-segment elevation myocardial infarction (STEMI)

Abstract Dual antiplatelet therapy is recommended in patients undergoing primary percutaneous coronary intervention (p-PCI) for ST-segment elevation myocardial infarction (STEMI). Pre-analytical variables may influence platelet function analysis results. Our aim was to evaluate the on-treatment platelet reactivity in peripheral artery vs coronary blood in patients with STEMI. We enrolled one hundred and nine patients who consecutively underwent p-PCI at Cardiology Unit of Padua University Hospital between June 2014 and June 2015. Before the procedure, all patients received intravenous aspirin 250 mg and either of the thienopyridines; clopidogrel 600 mg, prasugrel 60 mg or ticagrelor 180 mg. ASPI-test and ADP-test using multiple electrode aggregometry (MEA) were performed in samples collected from both a peripheral artery and the culprit coronary artery. ‘Low responders’ were patients with an ASPI-test or ADP-test value greater than or equal to a pre-established normal range. No significant differences were observed in ASPI-test values between peripheral (19 (median) [3–49 (10–90 percentiles)] U) vs coronary (12 [1–40] U, p = .06) blood and in ADP-test (40 [14–82] U vs 33 [7–79] U, p =.68) blood. In peripheral blood, fifteen (14%) patients were ‘low aspirin’ and forty-one (38%) ‘low thienopyridines’ responders. The prevalence of ‘low clopidogrel’ responders was higher (45%) than prasugrel (36%) and ticagrelor (33%). Similar results were observed in coronary blood. In patients undergoing p-PCI for STEMI, MEA platelet function observed in coronary arteries was consistent with peripheral artery blood’s independently of the antiplatelet drug used. The clinical significance of peripheral and coronary on-aspirin/thienopyridines platelet reactivity needs further clarification.

The diagnostic challenge: are we missing pulmonary embolism diagnosis in patients with syncope?

Syncope has been considered an uncommon presentation of pulmonary embolism (PE) accounting for less than 5% of cases [1–4]. The results of two recent studies published in the literature suggest that the prevalence of PE among patients hospitalized with syncope is even lower. Particularly, the General Medicine Inpatient (GEMINI) study retrospectively evaluated 1305 patients hospitalized with a first episode of syncope, and finds that PE prevalence is 0.84% [5]. In addition, a very recent retrospective, observational study by Costantino et al. [6] analyzed longitudinal administrative data from 5 databases in 4 different countries (Canada, Denmark, Italy, and the United States) for a total of 522,464 patients hospitalized for syncope and finds that PE diagnosis ranges from 0.15 to 2.10%. On the other hand, in the recently published Pulmonary Embolism in Syncope Italian Trial (PESIT) [7] that systematically and prospectively evaluated 560 patients admitted with a first episode of syncope, the prevalence of PE reaches 17.1%. In light of such discrepancies across multiple studies with different designs, it remains quite challenging for clinicians to evaluate the real impact of PE in patients hospitalized for syncope. We conducted a retrospective cohort study with the aim of assessing the incidence of PE 3 month post-discharge after a hospitalization for syncope. For the purpose of this study, we enrolled all patients hospitalized in a medical ward (both general medicine and subspecialty wards) between January 2014 and December 2015 after admission to the Emergency Department (ED) with a triage code of “syncope” at Padua University Hospital, Italy (a teaching hospital serving more than 200,000 inhabitants) and San Daniele del Friuli Hospital, Italy (a non-teaching hospital serving about 70,000 inhabitants). Exclusion criteria were the same as PESIT and GEMINI studies (i.e., previous episodes of syncope, ongoing anticoagulation therapy, and pregnancy) [5, 7]. The diagnosis of PE at hospital discharge and within 3 months of followup is the outcome. PE was established in the presence of positive computed tomographic pulmonary angiography (CTPA) or high probability ventilation/perfusion lung scanning. We analyzed our cohort’s medical records provided by the Veneto and Friuli Venezia Giulia Regional Health Department informatics system to gather data pertaining to clinical characteristics, D-dimer levels at admission, subsequent re-admissions for PE and deaths over a 3-month period after discharge. The study received research ethics board approval. We proceeded to calculate PE prevalence and associated 95% confidence interval [CI] during hospitalization, incidence of readmission for PE, overall mortality and mortality for PE during the follow-up. Student’s t test for continuous variables and Chi-square test for categorical variables were used to compare baseline characteristics between patients with and without PE. Unadjusted odds ratios (OR) with mid-p 95% CI were also calculated using 2 × 2 tables. All calculations were performed with OpenEpi 3.01. Out of 699 patients hospitalized with a triage code of “syncope” during the study period, 124 (17.7%) were excluded for ongoing anticoagulation, 119 (17.0%) for recurrent syncope and 3 (0.4%) for the presence of the latter two. Ultimately, 453 patients [mean age ± SD 76.7 ± 13.1, female 246 (54.3%)] were considered for the present analysis (Table 1 and Fig. 1). Clinical evidence suggested an explanation for syncope other than PE in 332 patients (73.3%). Fifty-five patients (12.1%) out of 453 * Paolo Simioni paolo.simioni@unipd.it