Thrombotic Events In Patients Research Articles

5-oxoETE promote thrombosis in antiphospholipid syndrome by triggering NETs formation through PLC/PKC/ERK pathway.

One mechanism by which antiphospholipid syndrome (APS) IgG contribute to thrombotic events in patients with APS is through the potentiation of neutrophil extracellular traps (NETs) release. However, the exact mechanism by which APS IgG induces NETs formation and thrombosis has not been fully elucidated. We conducted untargeted metabolomics on serum samples from thrombotic APS patients to identify metabolic changes. The effect of 5-oxoETE on NETs formation and oxidative stress was evaluated in vitro by treating neutrophils with various concentrations of 5-oxoETE. The involvement of the PLC/PKC/ERK signaling pathway in 5-oxoETE-induced NETs formation was examined using pharmacological inhibitors. In vivo, we assessed the effects of inhibiting 5-oxoETE synthesis or blocking its receptor (OXE-R) on NETs formation and thrombosis in APS mouse models. Serum metabolomics revealed significantly elevated levels of 5-oxoETE in APS patients. In vitro experiments demonstrated that 5-oxoETE, via OXE-R activation of the PLC/PKC/ERK signaling pathway, increased NETs formation and oxidative stress in a dose-dependent manner. In vivo, inhibiting 5-oxoETE synthesis or OXE-R reduced NETs formation and attenuated venous thrombosis in APS mice models. This study identifies 5-oxoETE as a critical mediator of NET formation and thrombosis in APS. Targeting 5-oxoETE or OXE-R may offer a promising therapeutic approach for thrombotic APS and other NET-associated autoimmune diseases.

Pharmacokinetics and Bioequivalence of a Generic Ticagrelor 90-mg Formulation Versus the Innovator Product in Healthy White Subjects Under Fasting Conditions.

Ticagrelor is a key antiplatelet agent used to prevent thrombotic events in patients with acute coronary syndrome. This open-label, 2-period, crossover Phase I study assessed the pharmacokinetics and bioequivalence of a generic ticagrelor 90-mg formulation compared to the innovator product under fasting conditions. Twenty-eight healthy White adults participated in the study. Each participant received a single dose of either the test or reference formulation, followed by a 7-day washout period before switching to the alternate formulation. Plasma concentrations of ticagrelor were measured using a validated high-performance liquid chromatography-tandem mass spectrometry method. Statistical analysis of primary pharmacokinetic parameters, including maximum concentration and area under the plasma concentration-time curve from time 0 to the last quantifiable concentration, showed bioequivalence with test/reference ratios of 110.9% and 107.1%, respectively, and 90% confidence intervals within the 80%-125% regulatory range. Treatment-emergent adverse events, such as headache, dysphagia, and dizziness, were moderate and transient and resolved promptly, with no significant difference in incidence between the formulations. These results confirm that the generic ticagrelor formulation is bioequivalent to the innovator product, supporting its use as an interchangeable option in clinical practice.

Utility of the modified Ottawa score for identification of more preferable candidates of extended anticoagulation therapy in cancer-associated isolated distal deep vein thrombosis: insight from the ONCO DVT Study

BackgroundThe ONCO DVT study (Edoxaban for 12 Months Versus 3 Months in Patients With Cancer With Isolated Distal Deep Vein Thrombosis) revealed superiority of 12-month relative to 3-month edoxaban treatment for the thrombotic risk in cancer-associated isolated distal deep vein thrombosis. However, it is unknown whether the superiority could be common in different modified Ottawa score subgroups. ObjectivesTo identify more preferable candidates for extended anticoagulation in patients with cancer-associated isolated distal deep vein thrombosis using the modified Ottawa score. MethodsIn this post-hoc subgroup analysis of the ONCO DVT study, we stratified 601 patients into the low (≤−1, N = 126), intermediate (0, N = 323), and high (≥1, N = 152) modified Ottawa score subgroups and compared clinical outcomes between the 12-month and 3-month edoxaban treatment groups. ResultsThe cumulative incidence of symptomatic recurrent venous thromboembolism or venous thromboembolism–related death was not different between the 12-month and 3-month edoxaban treatment groups in the low score subgroup (0.0% vs 2.2%), whereas it was lower in the 12-month than in the 3-month edoxaban treatment group in the intermediate (0.8% vs 7.6%) and high (3.1% vs 15.6%) score subgroups. There were no significant differences in the cumulative incidences of the major bleeding between the 12-month and 3-month edoxaban treatment groups in the low (10.1% vs 7.6%), intermediate (8.8% vs 5.0%), and high (13.9% vs 12.6%) score subgroups. ConclusionA 12-month compared with 3-month edoxaban treatment showed a lower risk of thrombotic events in patients with cancer-associated isolated distal deep vein thrombosis in the intermediate and high modified Ottawa score subgroups but not in the low score subgroup, suggesting a limited benefit of extended anticoagulation therapy beyond 3 months in patients with low modified Ottawa score.

Development and Validation of RP-HPLC Method for Estimation of Ticagrelor in Pharmaceutical Dosage Form and Force degradation study

Ticagrelor is a selective Adenosine diphosphate (ADP)-receptor antagonist which is prescribed in the form of tablets and acts as an oral antiplatelet for the prevention of further thrombotic events in patients with Acute coronary syndrome (ACS) and those undergoing Percutaneous coronary intervention (PCI). Therefore, accurate and reliable determination of Ticagrelor in bulk and in dosage forms is vital for clinical consideration. The objective of the method is to develop a new, simple, sensitive, accurate, and economical analytical method for the determination of assay of Ticagrelor Tablet and to perform a forced degradation study of Ticagrelor Tablet by RP-HPLC. Chromatographic separation was achieved on an UHPLC equipped with reverse phase C-18 (250 × 4.6mm, 5µ) with a mobile phase composed of acetonitrile and buffer solution (75:25) at a flow rate of 1.10 ml/min. The effluents were detected at a wavelength of 256 nm. The retention time of Ticagrelor was found to be at 3.579 min. The correlation coefficient for Ticagrelor was found to be 0.997. Recovery of Ticagrelor in the formulation was found to be 98%-102%. LOD and LOQ values of Ticagrelor were found to be 1.31 and 3.98, respectively. The method was proven to be precise (%RSD=2%), accurate (>90%), and specific for the measurement of Ticagrelor in tablets. Thus, being simple, accurate, precise, and rapid, the newly developed RP-HPLC method is recommended for the estimation of Ticagrelor in nature. Due to its high sensitivity and specificity, it is a suitable choice for identifying Ticagrelor in drugs and other products and differentiating hid similarities. However, this method can effectively be used for routine assay and stability study, which can help manage cardiovascular diseases since the quality and efficacy of Ticagrelor-containing products are significant to patients’ condition.

Milvexian: An Oral, Bioavailable Factor XIa Inhibitor.

Direct oral anticoagulants have a dose-dependent increased bleeding risk which limits use in certain populations. Studies in both animals and humans with inherited variations in factor XI levels provide a theoretical basis for a drug target capable of addressing current unmet needs. Milvexian is an oral factor XIa inhibitor that has the potential to provide robust anticoagulant effect without increased bleeding compared with current standard of care. Several key studies in the preclinical, phase I, and phase II stages have reported promising safety data in venous thromboembolism and stroke prevention without compromising hemostasis. The planned phase III trials will examine the efficacy of milvexian for prevention of thrombotic events in patients with acute stroke, acute coronary syndrome, and atrial fibrillation.

Association between JAK2V617F variable allele frequency and risk of thrombotic events in patients with myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPNs) are a group of chronic disorders of the bone marrow characterised by the overproduction of clonal myeloid stem cells. The most common driver mutation found in MPNs is a point mutation on exon 14 of the JAK2 gene, JAK2V617F. Various studies have suggested that measuring the variable allele frequency (VAF) of JAK2V617F may provide useful insight regarding diagnosis, treatment, risks and outcomes in MPN patients. In particular, JAK2V617F has been associated with increased risk of thrombotic events, a leading cause of mortality in MPNs. The aim of this study was to determine if JAK2V617F VAF was associated with clinical outcomes in patients with MPN. JAK2V617F VAF was determined by quantitative PCR (qPCR) in a cohort of 159 newly diagnosed MPN patients, and the association of JAK2V617F VAF and risk of thrombosis was examined in this cohort. We observed a significantly higher JAK2V617F VAF in PV and PMF versus ET. A significant association was observed between JAK2V617F VAF and risk of thrombotic events. When patients were stratified by thrombotic events prior to and post diagnosis, an association with JAK2V617F VAF was only observed with post diagnosis thrombotic events. Of note, these associations were not observed when looking at each MPN subtype in isolation. We have shown that a higher JAK2V617F VAF is associated with thrombotic events post MPN diagnosis. JAK2V617F VAF may therefore provide a valuable prognostic indicator for risk of thrombosis in MPNs.

Evaluation of the incidence, predictors, risk assessment scores and outcomes of thromboembolism in a cohort of Egyptian NHL patients - Real World Experience

Non-Hodgkin’s Lymphoma (NHL) is the most common subtype of lymphoma. The incidence of venous thromboembolism (VTE) in aggressive NHL was estimated recently to be 11%. Several risk assessment scores and factors are available to help identify cancer patients at risk for developing VTE. Patients with a pathologically confirmed diagnosis of NHL were identified at the Oncology Center of Mansoura University. The study included 777 patients: 719 with DLBCL-NOS, 26 with Anaplastic-B-cell, and 32 with T-cell-rich-NHL. Data were retrospectively collected from electronic medical records, including clinical, radiological, and laboratory information related to VTE and NHL. The median age at NHL diagnosis was 53 years, (range: 18–98). There was a male predominance, 51.4% of the cases. At initial lymphoma diagnosis, VTE was identified in 46 (5.9%) patients, and 61 (7.9%) patients experienced VTE while undergoing chemotherapy. According to logistic regression analysis, a PS (performance status) ≥ 2, bulky lesions, and mediastinal masses were significant predictors of VTE at presentation, with P-values of 0.022, 0.002, and < 0.001, respectively. Meanwhile, NHL patients who developed VTE during chemotherapy had significantly poorer PS, higher absolute neutrophilic counts (ANC), neutrophil/lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and lactate dehydrogenase (LDH) levels than lymphoma patients without VTE, with P-values of 0.003, 0.034, 0.049, 0.01 and 0.007, respectively, as determined by multivariate analysis. The ROC curve identified the cut-off values of 4.875 × 109/L for ANC, 2.985 for NLR, 144.85 for PLR, and 417.5 U/L for LDH as potential markers for predicting VTE in NHL patients. Patients with a PS ≥ 2 and values exceeding these cut-offs for ANC, NLR, and PLR experienced significantly higher incidences of VTE than other groups, with P-values of 0.003, < 0.001, < 0.001, and < 0.001, respectively. At the end of the follow-up, the overall survival was significantly shortened by VTE occurring during chemotherapy, hypoalbuminemia, intermediate-high and high international prognostic index (IPI) scores (intermediate-high and high), responses other than CR and relapse, all with P-values < 0.05. ECOG PS and Inflammatory markers such as NLR, PLR, and neutrophilic count could serve as predictors of the development of thrombotic events in patients with NHL-DLBCL. Additionally, the occurrence of VTE during chemotherapy is an independent poor prognostic marker for overall survival (OS).

Anticoagulant Use in COVID-19 Patients: A Longitudinal Study From Zanjan, Iran.

Background The mortality and morbidity of thrombotic events in patients with coronavirus disease 2019 (COVID-19) are increasing worldwide. The clinical impact of prophylactic anticoagulation regimens among these patients in Iran remains unclear. This study aimed to evaluate the use of prophylactic anticoagulants and outcomes among COVID-19 patients admitted to a tertiary referral hospital. Methodology Patients diagnosed with COVID-19 and hospitalized between March 20 and June 20, 2020, were included in this longitudinal study after obtaining informed consent. Demographic and clinical data were collected from the hospital information system and medical records. Outcomes during this period were also evaluated. The data were entered into the preparation checklist and analyzed using SPSS version 24 software (IBM Corp., Armonk, NY, USA), employing chi-square, Fisher's exact, and Mann-Whitney U tests. Results Of the 831 enrolled patients, 51.9% were female, and 10.6% needed to be admitted to the intensive care unit (ICU). The mean age of the patients was 57.16 ± 17.32 years, and the mortality rate was estimated to be 9.4%. Mortality rates were significantly higher at older ages, in men, patients with ICU admission, severe pulmonary involvement, malignancy, airway obstruction, ischemic heart disease, and previous cerebrovascular accidents. ICU admission and mortality were statistically significantly higher in those who received concurrent prophylactic anticoagulants and aspirin than in other individuals. Conclusions Our study demonstrated that administering prophylactic aspirin with or without anticoagulant agents in COVID-19 patients did not reduce mortality rates or ICU transfers. However, it is worth noting that anticoagulant prescription was associated with a decrease in ICU admissions, which could potentially alleviate the significantly higher mortality rates observed among ICU patients in this study. Further research is needed to explore the potential benefits of anticoagulants in COVID-19 treatment.

Rotational thromboelastometry predicts future bleeding events in patients with cirrhosis

Background and aims Patients with cirrhosis of the liver are in a delicate state of rebalanced haemostasis and are at risk of developing both bleeding and thrombotic complications. Conventional haemostatic tests are unable to predict bleeding and thrombosis in these patients. We aimed to explore the role of Rotational Thromboelastometry (ROTEM) in predicting bleeding and thrombotic events in patients with cirrhosis. Methods We conducted a prospective cohort study of patients with cirrhosis at two metropolitan hospitals. All patients underwent ROTEM analysis and were then followed to record any bleeding and thrombotic events. Univariate and multivariate logistic regression analyses were performed to explore associations with bleeding and thrombotic events. Results Nineteen of the 162 patients recruited experienced a bleeding event within one year of ROTEM analysis. On univariate analysis, maximum clot firmness (MCF) using both EXTEM and INTEM tests was significantly reduced in patients who had a bleeding event, compared to those who did not (50 mm vs. 57 mm, p < 0.01 and 48 mm vs. 54 mm, p < 0.01, respectively). In addition, on univariate analysis, clotting time (CT) in the INTEM test was prolonged in the bleeding group (214 s vs. 198 s, p = 0.01). On multivariate analysis, only MCFEX was a significant predictor of bleeding events. In contrast, there was no association found between ROTEM parameters and development of thrombosis within a one-year period. Conclusions ROTEM may provide a useful tool in predicting future bleeding events in patients with cirrhosis. Larger studies are required to further validate this finding and explore its application in clinical practice.

Antiplatelet effects of hydroxychloroquine in patients with systemic lupus erythematosus evaluated by the total thrombus-formation analysis system (T-TAS)

ObjectivesHydroxychloroquine (HCQ) has been shown to reduce thrombotic events in patients with SLE. However, the antiplatelet effects of HCQ are only supported by the platelet aggregation assay, which is a...

Protein C Pretreatment Protects Endothelial Cells from SARS-CoV-2-Induced Activation.

SARS-CoV-2 can induce vascular dysfunction and thrombotic events in patients with severe COVID-19; however, the cellular and molecular mechanisms behind these effects remain largely unknown. In this study, we used a combination of experimental and in silico approaches to investigate the role of PC in vascular and thrombotic events in COVID-19. Single-cell RNA-sequencing data from patients with COVID-19 and healthy subjects were obtained from the publicly available Gene Expression Omnibus (GEO) repository. In addition, HUVECs were treated with inactive protein C before exposure to SARS-CoV-2 infection or a severe COVID-19 serum. An RT-qPCR array containing 84 related genes was used, and the candidate genes obtained were evaluated. Activated protein C levels were measured using an ELISA kit. We identified at the single-cell level the expression of several pro-inflammatory and pro-coagulation genes in endothelial cells from the patients with COVID-19. Furthermore, we demonstrated that exposure to SARS-CoV-2 promoted transcriptional changes in HUVECs that were partly reversed by the activated protein C pretreatment. We also observed that the serum of severe COVID-19 had a significant amount of activated protein C that could protect endothelial cells from serum-induced activation. In conclusion, activated protein C protects endothelial cells from pro-inflammatory and pro-coagulant effects during exposure to the SARS-CoV-2 virus.

Andexanet alfa causes thrombotic events in patients with cerebral haemorrhage

Andexanet alfa causes thrombotic events in patients with cerebral haemorrhage

#2988 Use of rivaroxaban for prevention of thrombotic events in patients with nephrotic syndrome

Abstract Background and Aims Patients with nephrotic syndrome are at increased risk of thrombotic events. The risk of thromboembolism is particularly high in patients with primary membranous nephropathy, elderly patients and patients with severe hypoalbuminemia. Although increased incidence of thrombosis is a well reported complication associated with nephrotic syndrome, management strategies are not well established. Use of aspirin seems to be insufficient to prevent venous thromboembolism. Use of warfarin and low-molecular-weight heparins is inconvenient for outpatients. The aim of the trial was to evaluate effectiveness and safety of rivaroxaban in venous thromboembolism prophylaxis in patients with nephrotic syndrome. Method The randomized single-center trial was performed from October 2020 to November 2023. 30 adult patients with nephrotic syndrome due to primary glomerular diseases and glomerular filtration rate more than 60 ml/min were divided into two groups. The treatment group (n = 15) received 10-20 mg of rivaroxaban daily. The control group (n = 15) had no anticoagulation therapy. Thrombotic events and bleedings were recorded. Results Patients in both groups received immunosuppressive treatment of nephrotic syndrome according to primary disease. Rivaroxaban was prescribed for the entire treatment period until the onset of remission. Patients with membranous nephropathy were equally represented in both study groups (4 per group). No thromboembolic events were recorded in both groups. As well as there were no bleeding complications in patients who received rivaroxaban. Conclusion Rivaroxaban might be a possible alternative to warfarin and low-molecular-weight heparins in prevention of thrombosis in nephrotic syndrome. However, indications for anticoagulant prophylaxis, its duration and discontinuation are still not clear. Future studies should address the question regarding the utility of primary thromboprophylaxis.

Bleeding and thrombotic events and intensity of heparin therapy in the two first waves of COVID-19.

A systemic inflammatory response occurs during SARS-CoV2 infection and is associated with hypercoagulability and thrombotic events. From March 2020 in our hospital different dosages of low-molecular weight heparin (LMWH) were introduced according to the level of patient care intensity. Because bleeding episodes occurred in hospitalized COVID-19 patients on heparin, the dosage of LMWH at the end of first wave was tailored on the severity of COVID-19. The aim of this study is to describe bleeding and thrombotic events in patients hospitalized with SARS-CoV2 infection on LMWH therapy in the two waves of COVID-19 and analyze the factors associated with these events. Among 1143 patients enrolled in the COVID-19 Network registry, 912 were included in the analysis, 537 of them admitted during the first wave and 375 during the second. Bleeding events were 30 (3.3%): 22 (2.4%) major and 8 (0.9%) non-major. Arterial and venous thrombotic events were 6 (0.7%) and 24 (2.6%). The incidence of venous thrombotic events was higher in the first than in the second wave (0.29% [95% CI 0.20-0.45] events/day vs. 0.05% [95% CI 0.02-0.16]), with a 71% risk reduction (95% CI 22%-94%). The incidence of bleeding was 0.33% (95% CI 0.22-0.50) vs 0.14% events/day (95% CI 0.07-0.28), with no statistical between-wave difference (HR 0.41 95% CI 0.16-1.08). After adjusting for the competing risks of death and comorbidities, patients in the second wave had lower odds to have thrombotic events than in the first wave (0.24 HR [95% C.I. 0.07-0.89]). In this retrospective study on COVID-19 we found a low rate of hemorrhagic and thrombotic events, that may be explained by the absence in the case material of patients admitted to intensive care unit.

Cathepsin K deficiency prevented stress-related thrombosis in a mouse FeCl3 model

BackgroundExposure to chronic psychological stress (CPS) is a risk factor for thrombotic cardiocerebrovascular diseases (CCVDs). The expression and activity of the cysteine cathepsin K (CTSK) are upregulated in stressed cardiovascular tissues, and we investigated whether CTSK is involved in chronic stress-related thrombosis, focusing on stress serum-induced endothelial apoptosis.Methods and resultsEight-week-old wild-type male mice (CTSK+/+) randomly divided to non-stress and 3-week restraint stress groups received a left carotid artery iron chloride3 (FeCl3)-induced thrombosis injury for biological and morphological evaluations at specific timepoints. On day 21 post-stress/injury, the stress had enhanced the arterial thrombi weights and lengths, in addition to harmful alterations of plasma ADAMTS13, von Willebrand factor, and plasminogen activation inhibitor-1, plus injured-artery endothelial loss and CTSK protein/mRNA expression. The stressed CTSK+/+ mice had increased levels of injured arterial cleaved Notch1, Hes1, cleaved caspase8, matrix metalloproteinase-9/-2, angiotensin type 1 receptor, galactin3, p16IN4A, p22phox, gp91phox, intracellular adhesion molecule-1, TNF-α, MCP-1, and TLR-4 proteins and/or genes. Pharmacological and genetic inhibitions of CTSK ameliorated the stress-induced thrombus formation and the observed molecular and morphological changes. In cultured HUVECs, CTSK overexpression and silencing respectively increased and mitigated stressed-serum- and H2O2-induced apoptosis associated with apoptosis-related protein changes. Recombinant human CTSK degraded γ-secretase substrate in a dose-dependent manor and activated Notch1 and Hes1 expression upregulation.ConclusionsCTSK appeared to contribute to stress-related thrombosis in mice subjected to FeCl3 stress, possibly via the modulation of vascular inflammation, oxidative production and apoptosis, suggesting that CTSK could be an effective therapeutic target for CPS-related thrombotic events in patients with CCVDs.

Incidence of Arterial Thrombotic and Bleeding Events in Patients Who Develop Cancer after ST-elevation Myocardial Infarction.

Objective Cancers increase the risk of both arterial thrombosis and bleeding. The present study investigated whether or not comorbid new-onset cancers increase arterial thrombosis and bleeding events in patients after ST-elevation myocardial infarction (STEMI). Methods Among 918 consecutive STEMI patients, excluding 300 who used mechanical hemodynamic supportive devices, the 67 with cancer and 851 without cancer were compared with respect to the frequency of thrombotic events, consisting of myocardial infarction (MI) and ischemic stroke, and bleeding events during the trackable observation period in this observational study. The predictive accuracy for bleeding events evaluated by the Academic Research Consortium (ARC) high bleeding risk (HBR) criteria and the patients receiving stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score was assessed by C-statistics. Bleeding events were defined as type 3 or 5 according to the Bleeding Academic Research Consortium criteria. Results During the 1,233.3±1,284.4-day observation period, thrombotic events were observed in 13.4% of patients with cancer and 7.1% of patients without cancer (p=0.06; incidence rates, 2.4 vs. 2.4/100 person-years). MI and ischemic stroke were observed in 6.0% of patients with cancer and 3.5% of patients without cancer (p=0.23; incidence rates, 1.0 vs. 1.2/100 person-years) and 7.5% of patients with cancer and 3.6% of patients without cancer (p=0.18; incidence rates, 1.0 vs. 1.2/100 person-years), respectively. Bleeding events were observed in 26.9% of patients with cancer and 7.6% of patients without cancer (p<0.01; incidence rates, 4.4 vs. 2.4/100 person-years). The C-statistics for predicting bleeding events in patients with and without cancer were 0.65 vs. 0.71 using the ARC-HBR criteria and 0.67 vs. 0.71 using the PRECISE-DAPT scores, respectively. Conclusion Cancers increase unpredictable bleeding but not arterial thrombotic events in patients after STEMI.

Feasibility and Safety of Bridging Antiplatelet Therapy with Cangrelor in Neuro-Oncology: A Preliminary Experience.

Antiplatelet therapy is mandatory for prevention of thrombotic events in patients with a recent history of acute coronary syndromes and/or percutaneous coronary interventions. However, if an urgent surgery is required during antiplatelet therapy, a compromise between the ischemic/thrombotic and hemorrhagic risk has to be reached. Different bridging schemes are reported in the literature, but there is no clear consensus on the optimal treatment strategy in terms of efficacy and safety. Although some indications about the perioperative management of antiplatelet therapy regarding specific surgical specializations are available, balancing the thrombotic and hemorrhagic risk on an individual basis, no evidence referring to neurosurgical or neuro-oncologic procedures is reported. Herein, we present our preliminary experience in the perioperative management of a patient who underwent a neurosurgical procedure for the resection of a primary malignant brain tumor using an intravenous P2Y12 inhibitor (cangrelor) as bridging therapy after a recent acute myocardial infarction treated with primary percutaneous coronary intervention and stenting. The oral P2Y12 inhibitor (clopidogrel) was withdrawn 5 days prior to the surgical procedure and continuous infusion of cangrelor was started 3 days before the surgery at a dose of 0.75 μg/kg/min. Cangrelor was discontinued 2 hours before surgery and resumed 72 hours after tumor resection for further 60 hours. Neither cangrelor-related bleeding nor cardiac ischemic events were observed in the perioperative period and the following 90 days, supporting data regarding the feasibility and safety of this bridging scheme. Further studies are needed to confirm our promising results.

AF-React study: Prevalence of thrombotic events in patients with atrial fibrillation receiving NOACs - real-world data analysis from northern Portugal primary healthcare.

Anticoagulation is recommended for stroke prevention in patients with atrial fibrillation (AF). The guidelines suggest non-vitamin K antagonist anticoagulants (NOACs) as the primary therapy for anticoagulation in AF. Several patient-related factors increase the risk of thrombotic events: elderly individuals, a previous history of stroke, and chronic kidney disease. This study aims to determine the association between NOACs and other patient variables in AF and the occurrence of thrombotic events. The database included all adults with the code K78 (ICPC-2 code for AF) who received clinical care in Northern Portugal's Primary Health Care between January 2016 and December 2018 and were dispensed the same NOAC at the pharmacy. The results indicate that 10.2% of AF patients on NOAC anticoagulation experienced a stroke. Furthermore, patients treated with apixaban and dabigatran had higher odds of experiencing a stroke compared to those treated with rivaroxaban. Among patients with the same age, gender, and CHA2DS2Vasc Score, apixaban was significantly associated with a higher likelihood of thrombotic events than rivaroxaban. These results have not been previously reported in studies with real-world data; therefore, a more detailed analysis should be conducted to enhance the validity of these findings.

Recurrent splanchnic and extrasplanchnic thrombotic events in patients with non-cirrhotic portal vein thrombosis associated with local factors

One third of recent non-cirrhotic portal vein thrombosis are associated with local factors. The risk of rethrombosis after anticoagulation withdrawal is unknown. We aimed to determine factors associated with splanchnic or extrasplanchnic new thrombotic events in that setting. MethodsRetrospective study including recent non-cirrhotic portal vein thrombosis associated with local factors. High and low prothrombotic risk factors, prespecified according to Riport study criteria, were assessed. Quantitative and qualitative variables are presented as median (inter-quartile range), and absolute and relative frequencies respectively. Univariate and multivariate Cox models assessed the influence of different variables on the occurrence of a new thrombotic event. ResultsAt baseline, 83/154 (53.9%) had at least one prothrombotic factor including 50 (32.5%) high-risk and 33 (21.4%) low-risk prothrombotic factors. Oestrogen containing contraception was discontinued in all patients. During follow up, 63/140 (45%) patients had at least one prothrombotic factor, including 47 (33.6%) with a high risk, and 16 (11.4%) a low risk prothrombotic factor. Seventeen new thrombotic events occurred after a median follow-up of 52 (IQR 14-62) (min–max 3.0-69.0) months. New thrombosis were associated with high risk factors (HR 3.817, 95% CI [1.303-11.180], p= 0.015), but inversely related to recanalization (HR 0.222, 95% CI [0.078-0.635], p=0.005) and anticoagulation (HR 0.976, 95% CI [0.956-0.995], p=0.016). When a high-risk factor was present a new thrombotic event occurred in 7.4%, 14.6%, 14.6% and 28.8% of patients at 1, 3, 5 and 7 years under anticoagulants compared to 21.2%, 21.2%, 58% and 58% without anticoagulants. ConclusionsIn recent non-cirrhotic portal vein thrombosis associated with local factors, high risk factors for thrombosis are associated with new thrombotic events. Permanent anticoagulation appears beneficial in this high-risk situation. Impact and implicationsIn noncirrhotic portal vein thrombosis (NCPVT) associated with local factors, systematic screening for prothrombotic factors is recommended, but prevalence of the latter is not clearly established, and the risk of recurrent intra or extra splanchnic thromboembolism is poorly described. Thus, interest in permanent anticoagulation therapy is still pending.NCPVT associated with local factors, is a matter of concern for hepatologists, gastroenterologists and digestive surgeons. Due to a lack of knowledge, practices are heterogeneous.Our findings highlight that systematic screening for prothrombotic factors in NCPVT is strongly needed even when associated with local factors, as it may justify long-term anticoagulation therapy for the prevention of new intra or extra-splanchnic thrombotic events in at least one-third of cases.The interest in long-term anticoagulation should be investigated prospectively in the absence of prothrombotic factors with high risk of thrombosis. Clinical trial numberNCT0536064

Hypoalbuminemia as predictor of thrombotic events in patients with community-acquired pneumonia

BackgroundHypoalbuminemia complicates acute diseases and infections and is associated with a worst prognosis. The aim is to evaluate whether hypoalbuminemia is associated with higher incidence and risk of thrombotic events in community-acquired pneumonia. MethodsWe retrospectively collected data from a prospective study investigating the incidence of thrombotic events in community-acquired pneumonia hospitalized patients from 2011 to 2016 at University-Hospital Policlinico Umberto I. Baseline characteristics and outcomes were collected. Incidence of outcomes were calculated. Kaplan-Meier curves were created, Cox model used to identify predictors for the outcomes, and competing risk analysis performed. ResultsFrom a total of 231 patients, 130 (56.3%) and 101 (43.7%) had or not hypoalbuminemia. Age, proportion of female, BMI, major comorbidities, and severity of pneumonia were similar between two subgroups. A less proportion of patients with hypoalbuminemia received antithrombotic and statin therapy. Median hospital stay was 11 days in both subgroups. Patients with hypoalbuminemia had higher D-dimer and high- sensitivity C-reactive-protein values with an inverse relation between albumin values and these markers. Incidence of thrombotic events was 26 and 11 per 1000 patient-days in patient with and without hypoalbuminemia. At Cox model, hypoalbuminemia was associated with thrombotic events development in univariable (hazard ratio; 2.67, 95% confidence intervals, 1.30–5.40) and multivariable (hazard ratio 3.19; 95% confidence intervals, 1.48–6.89) analysis. ConclusionsMore than a half of patients with community acquired pneumonia had hypoalbuminemia that is associated with a doubled incidence and a three-fold increased risk of thrombotic events. The inverse relation between baseline albumin and D-dimer values confirms this association.