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Peri-operative antiplatelet therapy (APT) aims to prevent thrombotic events such as stroke. High platelet reactivity ,despite the use use of APT, increases the risk of thrombotic events. Transcranial Doppler imaging (TCD) is used to detect peri-operative microembolic signals (MES) during carotid endarterectomy (CEA). Peri-operative MES are associated with an increased risk of procedural stroke and new silent lesions on diffusion weighted magnetic resonance imaging following surgery. The main components of TCD detected MES are platelet aggregates, and therefore patients displaying multiple MES during surgery could have benefited from more stringent APT. This study investigated whether the use of flow cytometry based platelet reactivity measurements were correlated with the incidence of pre-operative MES and thereby in the future suitable to predict patients at increased risk of peri-operative thrombotic events. Bilateral TCD with MES detection was performed in 197 patients undergoing CEA. Platelet reactivity was assessed with a flow cytometry based platelet reactivity assay measuring platelet response in whole blood. High on treatment platelet reactivity status was assessed for all patients. The secondary outcome was major adverse cardiovascular events (MACE) within one year. In total, 197 patients were included, 49 had peri-operative MES. The platelet response to adenosine diphosphate (ADP) correlated with MES (p =.021), and high on treatment platelet reactivity after adenosine diphosphate stimulation was associated with MACE (OR 2.34, 95% confidence interval 1.126 – 4.890, p =.023). Pre-operative platelet reactivity determined by flow cytometry after ADP stimulation correlated with the occurrence of intra-operative MES and post-operative MACE. Clopidogrel treatment showed the most substantial effect on reducing MES frequency and platelet reactivity measured by flow cytometry. [ABSTRACT FROM AUTHOR]

COVID-19 is still a global challenge in regard for management and therapy. Pulmonary embolism (PE) seems to have a higher prevalence in COVID-19 instead of non-COVID patients. Clinical and laboratory parameters related with PE are still unknown. We conducted a retrospective unicentre study in Alto Vicentino Hospital between March 1st, 2020, and January 31st, 2021 in patients admitted for COVID-19 tested with a RT-PCR nasal swab. Data about patients studied with computed tomography pulmonary angiogram (CTPA) because of PE suspicion were collected, as their clinical and laboratory parameters too. 2621 patients were admitted for COVID-19 in Alto Vicentino Hospital between March 1st, 2020, and January 31st, 2021 and in 267 of them a CTPA was performed finding 50 PE (18.7%). Only non-Caucasian race (OR = 5.44; 95% CI 1.22–24.35; p = 0.027) and previous VTE (OR = 5.3; 95% CI 1.09–26.17; p = 0.039) were found to be independently associated with PE. PE is a frequent complication of COVID-19 and clinician need high degree of suspicion because clinical and laboratoristic parameters cannot drive diagnosis. • This study tries to find a correlation between COVID-19 and pulmonary embolism. • COVID-19 infection appears to be most correlated with thromboembolic events. • Unfortunately, clinical and laboratoristic parameters cannot drive diagnosis of pulmonary embolism in COVID-19 patients. [ABSTRACT FROM AUTHOR]

In intensive-care unit (ICU) patients, pathophysiological changes may affect the pharmacokinetics of enoxaparin and result in underdosing. To develop a pharmacokinetic model of enoxaparin to predict the time-exposure profiles of various thromboprophylactic regimens in COVID-19 ICU-patients. This was a retrospective study in ICUs of two French hospitals. Anti-Xa activities from consecutive patients with laboratory-confirmed SARS-CoV-2 infection treated with enoxaparin for the prevention or the treatment of venous thrombosis were used to develop a population pharmacokinetic model using non-linear mixed effects techniques. Monte Carlo simulations were then performed to predict enoxaparin exposure at steady-state after three days of administration. A total of 391 anti-Xa samples were measured in 95 patients. A one-compartment model with first-order kinetics best fitted the data. The covariate analysis showed that enoxaparin clearance (typical value 1.1 L.h-1) was related to renal function estimated by the CKD-EPI formula and volume of distribution (typical value 17.9 L) to actual body weight. Simulation of anti-Xa activities with enoxaparin 40 mg qd indicated that 64% of the patients had peak levels within the range 0.2 to 0.5 IU.mL-1 and 75% had 12-hour levels above 0.1 IU.mL-1. Administration of a total daily dose of at least 60 mg per day improved the probability of target attainment. In ICU COVID-19 patients, exposure to enoxaparin is reduced due to an increase in the volume of distribution and clearance. Consequently, enoxaparin 40 mg qd is suboptimal to attain thromboprophylactic anti-Xa levels. • Critical care COVID-19 patients are at high risk of venous thrombosis. • Population pharmacokinetics of enoxaparin in ICU COVID-19 patients were modeled. • Clearance and volume of distribution were high resulting in low anti-Xa exposure. • Enoxaparin 40 mg qd was suboptimal in ICU to attain thromboprophylactic target levels. [ABSTRACT FROM AUTHOR]

Pregnancy in women with a Fontan circulation is understood to have a significantly increased risk of maternal morbidity and mortality. Potential longer-term effects on health outcomes remain unknown. Ascertainment of adverse events, post-delivery, in women from the Australia and New Zealand (ANZ) Fontan Registry. Comparator data from women without pregnancy and men was utilised. Living adults were identified (n = 263 women, 280 men) with Registry analysis ascertaining cardiac morphology, type of Fontan procedure, pregnancy and significant cardiac adverse events. Data are described descriptively for morphology and as median (inter quartile range) for other variables. Thirty women reported 45 pregnancies beyond 20 weeks' gestation. Despite being older, these women, pre-delivery, had the lowest cardiac morbidity burden, compared to both male and female controls (OR = 3.25 (95% CI 1.44–8.35, p = 0.008 and OR = 2.59 (95% CI 1.14–6.70), p = 0.03). These differences were not present post-delivery. Median follow-up time post-delivery was 3.6 (1.2–7.5) years. Thrombus documentation and thromboembolic events were more common post-delivery, although differences were not significant in a propensity analysis model (adjusting for post-Fontan follow-up time, age and type of Fontan). There were no differences in arrhythmia, cardioversion, heart transplant, Fontan conversion or mortality between women post-delivery and either male or female controls. The apparent increase in thromboembolic events post pregnancy requires further investigation in a larger group of women over a longer period of follow-up time. This may have potential implications for post-partum anticoagulation, and for future health outcomes. • Pregnancy with a Fontan circulation is commoner among a healthier subgroup. • Pregnancy status did not differentiate Fontan conversion, transplantation, death-free survival outcome. • Thromboembolic events were commoner post delivery. • Matched data-sets are required to conclusively ascertain longterm maternal outcomes. [ABSTRACT FROM AUTHOR]

Abstract Background Low-molecular-weight heparins (LMWHs) are the recommended treatment for cancer-associated venous thrombosis (CAT). Recent evidences suggest a role for direct-acting oral anticoagulants (DOACs) in this clinical setting. Methods To evaluate the efficacy and safety of different anticoagulants we performed a network meta-analysis of RCTs including patients with CAT treated with LMWHs, vitamin K antagonists (VKAs) or DOACs. MEDLINE and EMBASE were searched up to February 2018. The primary efficacy and safety outcomes were recurrent VTE and major bleeding, respectively. Results Overall, 4720 CAT patients from 12 studies were included: 1430 from 2 studies comparing DOACs with LMWHs, 1212 from 4 studies comparing DOACs with VKAs and 2078 from 6 studies comparing VKAs to LMWHs. Recurrent VTE occurred in 4.9% of patients receiving DOACs, 9.6% receiving VKAs and 8.4% receiving LMWHs. The network meta-analysis showed a not significant increase of recurrent VTE in patients receiving LMWHs compared to those receiving DOACs (RR 1.3, 95% CI 0.9 to 2.0). The risk of recurrent VTE was higher in patients receiving VKAs compared to LMWHs (RR 1.5, 95% CI 1.0 to 2.0) or DOACs (RR 2.0, 95% CI 1.3 to 3.0) with no heterogeneity. Major bleeding occurred in 4.9, 4.1 and 4.3% of patients with CAT treated with DOAC, VKA or LMWH, respectively. No significant differences were observed from the direct, indirect and network meta-analyses. Conclusion In patients with CAT, DOACs showed a good efficacy and safety profile compared to other anticoagulants and is candidates to be an alternative to LMWHs. Highlights • The clinical benefit of DOACs in patients with cancer and venous thromboembolism (CAT) is debated. • We compared the use of DOACs, VKAs or LMWHs in 4720 patients with CAT. • Risk of recurrent VTE was 50% lower in patients who received DOACs compared VKAs. • Risk of recurrent VTE was 30% lower in patients who received LMWHs compared to VKAs. • Overall rates of major bleedings were similar among the 3 treatment groups. [ABSTRACT FROM AUTHOR]

Objective To evaluate the efficacy and bleeding complications associated with a low-dose thrombolysis protocol for thromboembolic lower extremity arterial occlusions. Design A retrospective cohort study. Materials and methods A retrospective analysis was performed using data from all consecutive patients who underwent catheter-directed, intra-arterial thrombolysis for thromboembolic lower extremity arterial occlusions between January 2004 and May 2013. All patients were treated on a standard surgical ward. Endpoints were incidence of bleeding complications, duration of thrombolysis, angiographic patency rate, 30-day mortality rate, and amputation-free rate at 6 months. Results Of the 171 cases analyzed, 129 cases underwent low-dose thrombolysis and 42 underwent high-dose thrombolysis. No major bleeding complications occurred in the low-dose group versus 5% in the high-dose group ( p = .01). The median duration of thrombolysis was 67 hours (4–304 hours) in the low-dose and 49 hours (2–171 hours) in the high-dose group ( p = .027). Angiographic patency was restored in 67% of the cases in the low-dose group versus 79% of the high-dose group ( p = .17). The 30-day mortality rates were 1% in the low-dose versus 5% in the high-dose group ( p = .09). However, this higher mortality rate was not related to bleeding complications. Major amputation-free rates at 6 months were 81% in the low-dose group and 88% in the high-dose group ( p = .22). Conclusions Based on this data series, low-dose thrombolysis for thromboembolic lower extremity arterial occlusions is as effective as high-dose thrombolysis; however, the risk of major bleeding complications is substantially lower when using low-dose thrombolysis. [ABSTRACT FROM AUTHOR]

Objective: Coiling of aneurysms 3 mm in diameter or less has been associated with a relatively high rate of complications, including iatrogenic rupture. The present study aimed to determine the clinical outcome of our technique for coiling small aneurysms. Methods: A retrospective chart review was performed of prospectively collected data for all patients who had endovascular coiling of an aneurysm 3 mm in diameter or less between 2003 and 2008. Follow-up imaging with magnetic resonance or catheter angiography was performed at varying intervals after coiling, ranging from 1 to 6 years after the procedure. Angiographic results were assessed using the Raymond-Roy (RR) grading system. Clinical outcomes during the same period were measured using the modified Rankin Scale. Results: Between March 2003 and April 2008, 20 patients underwent coil embolization of an aneurysm 3 mm or smaller—17 ruptured and 3 unruptured. After the procedure, 10 aneurysms were completely occluded (RR 1), 7 had residual filling of the neck (RR 2), and 3 had residual filling of the fundus (RR 3). There were no iatrogenic ruptures. Stent assistance was used in three cases. Balloon assistance was not used. Two patients were retreated, but no aneurysm reruptured. Clinical outcomes were as expected on the basis of the presenting Hunt & Hess grade. One patient with a ruptured aneurysm died from complications related to severe vasospasm. Conclusion: Aneurysms 3 mm in diameter or smaller can be coiled safely with the use of both bare platinum and hydrogel-coated coils. In most cases, coiling of small aneurysms can be performed without the use of adjunctive devices such as balloons or stents. [Copyright &y& Elsevier]

Abstract: Background and purpose: Inflammation plays an important role in the initiation and progression of atherosclerosis but the contribution of neutrophils to this process is unclear. Asymptomatic cerebral microembolization can be detected by transcranial Doppler (TCD) and has been associated with increased risk of early stroke recurrence in patients with recently symptomatic carotid stenosis. In the present study, we sought to determine whether spontaneous microembolization was associated with neutrophil count in patients with recently symptomatic carotid stenosis. Methods: We continuously monitored Transcranial Doppler (TCD) spectra of middle cerebral artery blood flow ipsilateral to recently symptomatic carotid artery stenosis in 60 consecutive patients. Microembolic signals (MES) were diagnosed by experienced observers blinded to leukocyte count and high-sensitive C-reactive protein (hs-CRP) level measurement. Results: We found MES in 20 (33.3%) patients. Microembolization was associated with higher neutrophil counts (p =0.003). Differences in monocyte count and lymphocyte count between patients with MES and patients without MES were not statistically significant. Microembolization remained strongly associated with neutrophil count in multivariable analysis (p =0.003) whereas the association with hs-CRP was not significant. Conclusions: Neutrophil count was associated with microembolization in patients with recently symptomatic carotid artery stenosis. Our findings suggest that neutrophils may play a role in the pathogenesis of stroke related to carotid atherosclerosis. [Copyright &y& Elsevier]

Background: Recurrent venous thromboembolism (RVTE) is a multifactorial disease with occurrence rates which vary from 13 % to 25 % in 5 years after the initial event. Once a patient the first thrombotic event, the probability of recurrence should be determined, as well as the most adequate anticoagulant therapy. To our knowledge based on the published literature, three statistical models have been proposed to calculate RVTE probability. However, these models present several limitations, such as: limited input variables, lack of external validation and applicability only for patients with a first unprovoked thrombosis. Additionally, some of the models have been recognized to fail in determining RVTE when patients have a low risk of recurrence.Objective: An alternative procedure in which three Artificial Neural Network (ANN) models were developed to classify which patients will present RVTE based solely on clinical data.Methods: Data of 39 clinical factors from 235 patients were used to train several ANN structures. The difference among the three models was its inputs. In ANN 1, the inputs were all 39 factors. In ANN 2, 18 factors determined previously as the main predictors of RTVE using Principal Component Analysis (PCA). Finally, in ANN 3, 15 factors combining PCA results with practical aspects. Different number of hidden layers and neurons, and three optimization algorithms were considered. 5-fold cross validation was also performed.Results: The results showed that all models were capable of performing this task. Different optimization algorithms lead to different results. The best models presented high accuracy. The best structures were 39-10-10-1, 18-10-5-1, and 15-15-10-1 for ANN 1, ANN 2, and ANN 3 models, respectively. The cross-validation showed that the results are consistent.Conclusions: This work showed that the association of multivariate techniques and ANNs is a powerful tool that can be used to model a complex phenomenon such as RVTE without the restrictions of existing approaches.Application: After proper validation, these ANN models can be used to help clinicians with decisions regarding VTE treatment. [ABSTRACT FROM AUTHOR]