Lipid lowering for prevention of venous thromboembolism: a network meta-analysis.

BACKGROUND AND AIMS: Studies have suggested that statins may be associated with reduced risk of venous thromboembolism (VTE). The aim of the current study was to assess the evidence regarding the comparative effect of all lipid-lowering therapies (LLT) in primary VTE prevention. METHODS: After a systematic search of PubMed, CENTRAL, and Web of Science up until 2 November 2022, randomized controlled trials (RCT) of statins (high- or low-/moderate-intensity), ezetimibe, or proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) were selected. An additive component network meta-analysis to compare VTE risk during long-term follow-up across different combinations of LLT was performed. RESULTS: Forty-five RCTs (n = 254 933 patients) were identified, reporting a total of 2084 VTE events. Compared with placebo, the combination of PCSK9i with high-intensity statin was associated with the largest reduction in VTE risk (risk ratio [RR] 0.59; 95% confidence interval [CI] 0.43-0.80), while there was a trend towards reduction for high-intensity (0.84; 0.70-1.02) and low-/moderate-intensity (0.89; 0.79-1.00) statin monotherapy. Ezetimibe monotherapy did not affect the VTE risk (1.04; 0.83-1.30). There was a gradual increase in the summary effect of VTE reduction with increasing intensity of the LLT. When compared with low-/moderate-intensity statin monotherapy, the combination of PCSK9i and high-intensity statin was significantly more likely to reduce VTE risk (0.66; 0.49-0.89). CONCLUSIONS: The present meta-analysis of RCTs suggests that LLT may have a potential for VTE prevention, particularly in high-intensity dosing and in combination therapy.

Edoxaban for 12 Months Versus 3 Months in Patients With Cancer With Isolated Distal Deep Vein Thrombosis (ONCO DVT Study): An Open-Label, Multicenter, Randomized Clinical Trial.

BACKGROUND: The optimal duration of anticoagulation therapy for isolated distal deep vein thrombosis in patients with cancer is clinically relevant, but the evidence is lacking. The prolonged anticoagulation therapy could have a potential benefit for prevention of thrombotic events; however, it could also increase the risk of bleeding. METHODS: In a multicenter, open-label, adjudicator-blinded, randomized clinical trial at 60 institutions in Japan, we randomly assigned patients with cancer with isolated distal deep vein thrombosis, in a 1-to-1 ratio, to receive either a 12-month or 3-month edoxaban treatment. The primary end point was a composite of a symptomatic recurrent venous thromboembolism (VTE) or VTE-related death at 12 months. The major secondary end point was major bleeding at 12 months, according to the criteria of the International Society on Thrombosis and Haemostasis. The primary hypothesis was that a 12-month edoxaban treatment was superior to a 3-month edoxaban treatment with respect to the primary end point. RESULTS: From April 2019 through June 2022, 604 patients were randomized, and after excluding 3 patients who withdrew consent, 601 patients were included in the intention-to-treat population: 296 patients in the 12-month edoxaban group and 305 patients in the 3-month edoxaban group. The mean age was 70.8 years, 28% of the patients were men, and 20% of the patients had symptoms of deep vein thrombosis at baseline. The primary end point of a symptomatic recurrent VTE event or VTE-related death occurred in 3 of the 296 patients (1.0%) in the 12-month edoxaban group and in 22 of the 305 patients (7.2%) in the 3-month edoxaban group (odds ratio, 0.13; 95% CI, 0.03-0.44). The major secondary end point of major bleeding occurred in 28 of the 296 patients (9.5%) in the 12-month edoxaban group and in 22 of the 305 patients (7.2%) in the 3-month edoxaban group (odds ratio, 1.34; 95% CI, 0.75-2.41). The prespecified subgroups did not affect the estimates on the primary end point. CONCLUSIONS: In patients with cancer with isolated distal deep vein thrombosis, 12 months was superior to 3 months for an edoxaban treatment with respect to the composite outcome of a symptomatic recurrent VTE or VTE-related death. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03895502.

HOXD9 regulated mitophagy to promote endothelial progenitor cells angiogenesis and deep vein thrombosis recanalization and resolution.

BACKGROUND: Deep vein thrombosis (DVT) is a common vascular surgical disease caused by the coagulation of blood in the deep veins, and predominantly occur in the lower limbs. Endothelial progenitor cells (EPCs) are multi-functional stem cells, which are precursors of vascular endothelial cells. EPCs have gradually evolved into a promising treatment strategy for promoting deep vein thrombus dissolution and recanalization through the stimulation of various physical and chemical factors. METHODS: In this study, we utilized a mouse DVT model and performed several experiments including qRT-PCR, Western blot, tube formation, wound healing, Transwell assay, immunofluorescence, flow cytometry analysis, and immunoprecipitation to investigate the role of HOXD9 in the function of EPCs cells. The therapeutic effect of EPCs overexpressing HOXD9 on the DVT model and its mechanism were also explored. RESULTS: Overexpression of HOXD9 significantly enhanced the angiogenesis and migration abilities of EPCs, while inhibiting cell apoptosis. Additionally, results indicated that HOXD9 specifically targeted the HRD1 promoter region and regulated the downstream PINK1-mediated mitophagy. Interestingly, intravenous injection of EPCs overexpressing HOXD9 into mice promoted thrombus dissolution and recanalization, significantly decreasing venous thrombosis. CONCLUSIONS: The findings of this study reveal that HOXD9 plays a pivotal role in stimulating vascular formation in endothelial progenitor cells, indicating its potential as a therapeutic target for DVT management.

Reducing thrombotic risks in video gamers: investigating the benefits of walking and compression sleeves on blood hemodynamics.

With the growing popularity of video gaming, deep vein thromboses are increasingly being reported in gamers. This study aimed to compare the effects of lower leg graduated compression sleeves and a 6-min walking break during prolonged gaming on blood flow and hemodynamics in competitive sport players to help mitigate this risk. Ten healthy gamers (19.6 ± 1.2 yr old; 9 men) consented to participate in this mixed-model crossover design study that consisted of three visits. In visit 1, participants engaged in continuous 2-h video game play wearing no compression (continuous). Visits 2 and 3 involved 2-h play wearing compression sleeves (compression) and 2-h game play interrupted at 1 h by a 6-min walk (walk). Doppler ultrasound measurements of the left popliteal artery were taken at 30, 60, 90, and 120 min, to record vessel diameter, blood flow velocity, and blood flow volume. Participants completed a survey to assess their perception of each approach. There was a significant interaction between conditions for blood flow and blood velocity (P = 0.01, P < 0.001). Post hoc analysis demonstrated a greater decrease in blood flow and blood velocity in the continuous group compared with the walk group at the 90-min mark (P = 0.04, P = 0.01). No differences were found between the compression and walk groups or between the continuous and compression groups (P = 0.42, P = 0.69). No interactions were observed in diameter, mean arterial pressure, or heart rate. This study suggests that incorporating a 6-min walk every 60 min during prolonged gaming is advisable to counteract the negative effects on blood flow hemodynamics.NEW & NOTEWORTHY A 6-min light-intensity walking break during gaming can effectively combat the adverse effects of prolonged sitting, surpassing compression garments. Prolonged sitting reduces blood flow velocity, potentially leading to deep vein thrombosis (DVT). Compression sleeves help, with superior results after a 6-min walk at 60 min. Although compression stockings offer moderate improvements, a 6-min active break proves more effective. These findings offer promising interventions for gamers' health, initiating guidelines to mitigate DVT risk during gaming.

Acute venous thromboembolism plasma and red blood cell metabolomic profiling reveals potential new early diagnostic biomarkers: observational clinical study.

BACKGROUND: Venous thromboembolism (VTE) is a leading cause of cardiovascular mortality. The diagnosis of acute VTE is based on complex imaging exams due to the lack of biomarkers. Recent multi-omics based research has contributed to the development of novel biomarkers in cardiovascular diseases. Our aim was to determine whether patients with acute VTE have differences in the metabolomic profile compared to non-acute VTE. METHODS: This observational trial included 62 patients with clinical suspicion of acute deep vein thrombosis or pulmonary embolism, admitted to the emergency room. There were 50 patients diagnosed with acute VTE and 12 with non-acute VTE conditions and no significant differences were found between the two groups for clinical and demographic characteristics. Metabolomics assays identified and quantified a final number of 91 metabolites in plasma and 55 metabolites in red blood cells (RBCs). Plasma from acute VTE patients expressed tendency to a specific metabolomic signature, with univariate analyses revealing 23 significantly different molecules between acute VTE patients and controls (p < 0.05). The most relevant metabolic pathway with the strongest impact on the acute VTE phenotype was D-glutamine and D-glutamate (p = 0.001, false discovery rate = 0.06). RBCs revealed a specific metabolomic signature in patients with a confirmed diagnosis of DVT or PE that distinguished them from other acutely diseased patients, represented by 20 significantly higher metabolites and four lower metabolites. Three of those metabolites revealed high performant ROC curves, including adenosine 3',5'-diphosphate (AUC 0.983), glutathione (AUC 0.923), and adenine (AUC 0.91). Overall, the metabolic pathway most impacting to the differences observed in the RBCs was the purine metabolism (p = 0.000354, false discovery rate = 0.68). CONCLUSIONS: Our findings show that metabolite differences exist between acute VTE and nonacute VTE patients admitted to the ER in the early phases. Three potential biomarkers obtained from RBCs showed high performance for acute VTE diagnosis. Further studies should investigate accessible laboratory methods for the future daily practice usefulness of these metabolites for the early diagnosis of acute VTE in the ER.

Venous Thromboembolism in Peritoneal Mesothelioma: Uncovering the Hidden Risk.

INTRODUCTION: Venous thromboembolism (VTE) is a common complication in patients with abdominal malignancies. Despite known associations between pleural mesothelioma and increased VTE risk, the characteristics of VTE in patients with peritoneal mesothelioma (PeM) remain undescribed. METHODS: Patients treated for PeM were retrospectively identified from our institutional database. The frequency of VTE was assessed and logistic regression modeling was employed to assess VTE risk factors. The association between VTE and overall survival was also ascertained. Recommended thromboprophylaxis for patients who underwent surgery at our institution comprised a single preoperative dose of prophylactic anticoagulation, followed by daily dosing for four weeks postoperatively. RESULTS: Among 120 PeM patients, 26 (21.7%) experienced VTE, including 19/91 (20.9%) surgical patients, 4/23 (17.4%) patients who received systemic therapy, and 3/6 (50%) patients who underwent observation (p = 0.21). Most events were symptomatic (n = 16, 62%) and were attributable to pulmonary emboli (n = 16, 62%). The 90-day postoperative VTE rate was 4.4% (4/91), including 1 of 60 patients who underwent index surgical intervention at our institution and 3 patients with surgery elsewhere. A low serum albumin concentration was associated with VTE in non-surgical patients (odds ratio 0.12, confidence interval [CI] 0.02-0.72; p = 0.03). No significant difference in overall survival was observed between patients with and without VTE (median 46.0 months [CI 24.9-67.0] vs. 55.0 months [CI 27.5-82.5]; hazard ratio 0.98 [CI 0.54-1.81], p = 0.98). CONCLUSIONS: A high risk of VTE was observed in PeM patients, warranting suspicion throughout the disease trajectory. Postoperative VTE rates were within acceptable limits with 4-week thromboprophylaxis.

Catheter-related deep vein thrombosis: Where are we at and where are we going? Updates and ongoing unmet clinical needs.

BACKGROUND: Catheter-related thrombosis (CRT) is one of the major complications affecting patients with indwelling venous catheters, usually involving the upper extremity deep venous system. This condition can lead to potentially life-threatening complications such as pulmonary embolism and sepsis. The risk of developing CRT varies depending on type of catheters and patient characteristics. Despite advances in materials and technologies, the actual incidence of CRT is still considerable. Available evidence on CRT management remains controversial, and clinical guidelines base their recommendations on data from non-catheter related upper extremity or lower extremity deep venous thromboses. AIMS: This narrative review aims to describe the epidemiology of CRT, to review the available evidence on its management and to highlight the current unmet needs. METHODS: No formal search strategy was applied for the revision of the literature. The main sources of information used were Medline and guidelines from international societies. CONTENT: The management of CRT requires a careful balance between the risk of thrombus progression, recurrent events, and systemic embolization and the increased bleeding risk in often fragile patients. Open issues include the optimal management of the catheter and the type and duration of anticoagulant therapy. Direct oral anticoagulants are increasingly prescribed, representing an important alternative to the standard of care low molecular weight heparins in selected cases. The development of new anticoagulant drugs such as factors XI and XII inhibitors may offer further advantages in this context. CONCLUSIONS: The management of CRT is still challenging with constant need for updated evidence to support tailored approaches.

Awareness and associated factors of venous thromboembolism in breast cancer surgical patients: a cross-sectional study.

BACKGROUND: Venous thromboembolism (VTE) is a major complication of breast cancer surgical patients. Assessing VTE awareness enables medical staff to tailor educational programs that improve patient self-management and reduce VTE risk. Therefore, this study aimed to assess VTE awareness among breast cancer surgical patients and identify factors influencing their awareness level. METHODS: A multicenter cross-sectional study was conducted on breast cancer patients scheduled for surgery from May 2023 to November 2023. Data were collected using a general information form and a validated self-assessment questionnaire on VTE awareness for breast cancer surgical patients. Univariate analysis and multiple linear regression analysis were used to analyze the data. RESULTS: Of 1969 patients included, the term awareness rates for deep vein thrombosis and pulmonary embolism were 42.5% and 26.1%, respectively. Information about VTE was primarily obtained from doctors (30.4%), nurses (24.0%), and social media (23.3%). The overall average VTE awareness score was 1.55 ± 0.53, with the dimension of VTE preventive measures scoring highest, and VTE clinical symptoms/signs scoring lowest. Multivariate analysis identified education level, personal VTE history, chemotherapy and surgical history, and the hospital's regional location as significant factors associated with VTE awareness level (p < 0.05). CONCLUSION: This study highlights a critical need for improved VTE awareness among breast cancer surgical patients, particularly regarding clinical symptoms/signs. Health education programs are recommended especially tailored for patients with lower education levels, no history of VTE, or without prior surgery or chemotherapy, to improve their understanding of VTE.

Incidence and risk factors for deep vein thrombosis (DVT) and pulmonary embolism (PE) in acute necrotizing pancreatitis (ANP) - A single center experience.

INTRODUCTION: Inflammation-induced dysregulation of the coagulation cascade and vascular stasis in hospitalized patients with acute necrotizing pancreatitis (ANP) serve as a milieu for venous thromboembolism (VTE). Deep vein thrombosis (DVT) and pulmonary embolism (PE) are often underrecognized. We evaluated the incidence and risk factors for VTE in a cohort of patients with ANP. METHODS: All adult patients with ANP at our center between 2009 and 2022 were followed for three months after index hospitalization and categorized into cases and controls based on development of VTE. Demographic, clinical, and radiologic characteristics during admission were compared. A multivariable analysis was done to identify independent predictors for VTE. A p value of <0.05 was taken as significant. RESULTS: Among 643 ANP patients, 512 [males-350, median age-52 years] were eligible for inclusion. VTE developed in 64 (12.5 %) patients - 28 DVT (5 %), 22 PE (4 %) and both in 14 (3 %) after a median 16 days from the diagnosis of ANP. Significant independent predictors for VTE on multivariable analysis were age ≥60 years (OR 1.91; 95 % CI 1.04-3.53), peri-pancreatic extent of necrosis (OR 7.61; 95 % CI 3.94-14.70), infected necrosis (OR 2.26; 95 % CI 1.13-4.50) and total length of stay ≥14 days (OR 4.08; 95 % CI 1.75-9.50). CONCLUSIONS: The overall incidence of VTE in our cohort of patients with ANP was 12.5 %, which was usually diagnosed within one month of hospitalization. High-risk patients can be stratified based on clinical and imaging characteristics and may benefit from intensive DVT screening and prophylaxis during hospitalization and following discharge.

Predicting VTE and utility of thromboprophylaxis in metastatic and recurrent cervical cancer.

OBJECTIVE: Patients with cervical cancer who are diagnosed with venous thromboembolism (VTE) have worse outcomes compared to those not affected. There has yet to be a reliable method to predict or prevent VTE in cervical cancer patients. Our objective is to describe the incidence of VTE in patients with recurrent and metastatic (r/mCC) and determine risk factors that may predict VTE in this setting. METHODS: We performed an observational cohort study of 386 patients with r/mCC who received at least one line of systemic chemotherapy. We collected demographic, clinical, histologic data and Khorana scores for all patients. Inclusion and exclusion criteria were applied before analysis. Statistical analysis was performed using Pearson chi-square, Student's t-test, and Wilcoxon rank-sum. RESULTS: 232 patients were included for evaluation. Mean age was 49 years (range 20-83). The majority (167, 72%) of patients had squamous cell histology. 169 (72.8%) patients received treatment for recurrent disease and 63 (27.2%) for metastatic, stage IVB disease. 180 (78%) patients received prior radiation and 134 (58%) received bevacizumab. VTE was diagnosed in 89 (38%) patients. There were no statistically significant differences amongst clinical and pathologic characteristics between patients who developed VTE and those who did not. There was no significant association between BMI, Khorana score, radiation, bevacizumab, or immunotherapy and the development of VTE. CONCLUSION: Approximately 40% of patients with r/mCC experienced a new VTE. There were no independent risk factors that could predict VTE in this population. Due to the overwhelmingly high incidence of VTE, prophylactic anticoagulation could be strongly considered in patients with r/mCC.