Network pharmacological and molecular docking verification of the mechanism of Osteoking in preventing deep vein thrombosis of lower limb.

OBJECTIVE: The aim of this study was to predict the mechanism of Osteoking in preventing deep vein thrombosis (DVT) of the lower limb by network pharmacology and molecular docking. MATERIALS AND METHODS: The relevant active components and targets of Osteoking were collected through the TCMSP database, and the relevant disease targets of DVT were collected through the GeneCards, OMIM, and DisGeNET databases. The intersecting gene targets of Osteoking and DVT were obtained using Venny 2.1.0 software. PPI network construction and core target selection using Cytoscape 3.9.0 software. The Metascape database was used for GO and KEGG enrichment analysis of relevant targets. Finally, the molecular docking of the main active components and key targets was carried out. RESULTS: There are 361 potential targets and 71 core targets of Osteoking in preventing deep vein thrombosis of the lower limb. Signal pathways are involved in various diseases such as cancer, diabetic complications, atherosclerosis, and more. Some of the most common pathways include AGE-RAGE signaling pathway and Calcium signaling pathway. Molecular docking results showed that the main active components of Osteoking had relatively stable binding activities with the key targets. CONCLUSIONS: Osteoking can play a role through multiple targets and multiple signal pathways to prevent the formation of deep venous thrombosis of the lower limb after fracture.

Efficacy and safety of salvianolate and enoxaparin in the prevention of perioperative deep venous thrombosis in gastrointestinal surgery.

OBJECTIVE: In this study, the efficacy and safety of salvianolate were compared with enoxaparin in the prevention of perioperative deep vein thrombosis in gastrointestinal surgery. METHODS: From October 2017 to September 2019, 563 patients who underwent gastrointestinal surgery were collected. Based on the inclusion and exclusion criteria, 119 patients were divided into two groups: enoxaparin group (n = 65) and salvianolate group (n = 54). Comparisons were made regarding the outcomes: prothrombin time (PT), prothrombin activity (PTA), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time (TT), D-dimer level (D-D), platelet count (PLT), hematokrit (HCT), and incidence of deep vein thrombosis (DVT). RESULTS: The main outcomes showed no significance between enoxaparin group and salvianolate group (p > .05). The incidence of DVT in salvianolate group was 1.85%, significantly lower than that in enoxaparin group (12.3%) (p < .05). No serious adverse reactions occurred in the two groups during treatment. CONCLUSION: Compared with enoxaparin, salvianolate has an advantage in the prevention of perioperative thrombosis in gastrointestinal surgery with a lower incidence of DVT.

Prevention of Deep Vein Thrombosis by Panax Notoginseng Saponins Combined with Low-Molecular-Weight Heparin in Surgical Patients.

OBJECTIVE: To evaluate the efficacy of deep vein thrombosis (DVT) prevention among real-world surgical inpatients who received panax notoginseng saponins (PNS) combined with low-molecular-weight heparin (LMWH). METHODS: A prospective cohort study was conducted among surgical patients between January 2016 and November 2018 in Xuanwu Hospital, Capital Medical University, Beijing, China. Participants received LMWH alone or PNS combined with LMWH for preventing DVT. The primary outcome was incidence of lower extremity DVT, which was screened once a week. Participants in the LMWH group were given LMWH (enoxaparin) via hypodermic injection, 4000-8000 AxalU once daily. Participants in the exposure group received PNS (Xuesaitong oral tablets, 100 mg, 3 times daily) combined with LMWH given the same as LMWH group. RESULTS: Of the 325 patients screened for the study, 281 participants were included in the final analysis. The cohort was divided into PNS + LMWH group and LMWH group with 134 and 147 participants, respectively. There was a significant difference of DVT incidence between two groups (P=0.01), with 21 (15.7%) incident DVT in the PNS + LMWH group, and 41 (27.9%) incident DVT in the LMWH group. Compared with participants without DVT, the participants diagnosed with DVT were older and had higher D-dimer level. The multivariate logistic regression model showed a significant lower risk of incident DVT among participants in the PNS + LMWH group compared with the LMWH group (odds ratio 0.46, 95% confidence interval, 0.25-0.86). There were no significant differences in thromboelaslography values (including R, K, Angle, and MA) and differences in severe bleeding between two groups. No symptomatic pulmonary embolism occurred during the study. CONCLUSION: Combined application of PNS and LMWH can effectively reduce the incidence of DVT among surgical inpatients compared with LMWH monotherapy, without increased risk of bleeding.

Therapeutic or prophylactic anticoagulation in acute isolated distal deep vein thrombosis: protocol for a prospective, multicentre, single-blind, randomised controlled trial (TOP-IDDVT).

INTRODUCTION: The efficacy and safety of anticoagulant treatment is not established for patients with acute symptomatic isolated distal deep vein thrombosis (IDDVT). In real-world clinical practice, both therapeutic and prophylactic anticoagulation are used for acute IDDVT. However, therapeutic anticoagulation is associated with higher risk of bleeding than prophylactic anticoagulation. Thus, this study aims to assess the efficacy and safety in patients with first acute symptomatic IDDVT treated with therapeutic or prophylactic anticoagulation using rivaroxaban. METHODS AND ANALYSIS: This study is a prospective, multicentre, single-blind, randomised controlled trial. Outpatients with a first, acute, symptomatic, objectively confirmed IDDVT in four centres from 1 August 2021 are recruited. Eligible patients are randomised in a 1:1 ratio to receive prophylactic anticoagulation (rivaroxaban 10 mg once a day for 3 months) or therapeutic anticoagulation (rivaroxaban 20 mg once a day for 3 months). All patients are followed for 6 months. The primary efficacy outcome is radiographically confirmed recurrent venous thromboembolism. The primary safety outcome is the incidence of major or clinically relevant non-major bleeding events. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of Zhongshan Hospital Fudan University (B2021-175R). Study results will be disseminated through peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04967573.

Effective prediction model for preventing postoperative deep vein thrombosis during bladder cancer treatment.

OBJECTIVE: To begin to understand how to prevent deep vein thrombosis (DVT) after an innovative operation termed intracorporeal laparoscopic reconstruction of detenial sigmoid neobladder, we explored the factors that influence DVT following surgery, with the aim of constructing a model for predicting DVT occurrence. METHODS: This retrospective study included 151 bladder cancer patients who underwent intracorporeal laparoscopic reconstruction of detenial sigmoid neobladder. Data describing general clinical characteristics and other common parameters were collected and analyzed. Thereafter, we generated model evaluation curves and finally cross-validated their extrapolations. RESULTS: Age and body mass index were risk factors for DVT, whereas postoperative use of hemostatic agents and postoperative passive muscle massage were significant protective factors. Model evaluation curves showed that the model had high accuracy and little bias. Cross-validation affirmed the accuracy of our model. CONCLUSION: The prediction model constructed herein was highly accurate and had little bias; thus, it can be used to predict the likelihood of developing DVT after surgery.

Prevention of Deep Vein Thrombosis by Panax Notoginseng Saponins Combined with Low-Molecular-Weight Heparin in Surgical Patients / 中国结合医学杂志

OBJECTIVE@#To evaluate the efficacy of deep vein thrombosis (DVT) prevention among real-world surgical inpatients who received panax notoginseng saponins (PNS) combined with low-molecular-weight heparin (LMWH).@*METHODS@#A prospective cohort study was conducted among surgical patients between January 2016 and November 2018 in Xuanwu Hospital, Capital Medical University, Beijing, China. Participants received LMWH alone or PNS combined with LMWH for preventing DVT. The primary outcome was incidence of lower extremity DVT, which was screened once a week. Participants in the LMWH group were given LMWH (enoxaparin) via hypodermic injection, 4000-8000 AxalU once daily. Participants in the exposure group received PNS (Xuesaitong oral tablets, 100 mg, 3 times daily) combined with LMWH given the same as LMWH group.@*RESULTS@#Of the 325 patients screened for the study, 281 participants were included in the final analysis. The cohort was divided into PNS + LMWH group and LMWH group with 134 and 147 participants, respectively. There was a significant difference of DVT incidence between two groups (P=0.01), with 21 (15.7%) incident DVT in the PNS + LMWH group, and 41 (27.9%) incident DVT in the LMWH group. Compared with participants without DVT, the participants diagnosed with DVT were older and had higher D-dimer level. The multivariate logistic regression model showed a significant lower risk of incident DVT among participants in the PNS + LMWH group compared with the LMWH group (odds ratio 0.46, 95% confidence interval, 0.25-0.86). There were no significant differences in thromboelaslography values (including R, K, Angle, and MA) and differences in severe bleeding between two groups. No symptomatic pulmonary embolism occurred during the study.@*CONCLUSION@#Combined application of PNS and LMWH can effectively reduce the incidence of DVT among surgical inpatients compared with LMWH monotherapy, without increased risk of bleeding.

Aqueous extract of Paeoniae Radix Rubra prevents deep vein thrombosis by ameliorating inflammation through inhibiting GSK3ß activity.

BACKGROUND: Deep vein thrombosis (DVT) is a kind of blood stasis syndrome. Paeoniae Radix Rubra (PRR) has long been widely used for eliminating blood stasis in China, but its effect on DVT has not yet been reported. PURPOSE: The present study aimed to assess the potential inhibitory effect of the aqueous extract of PRR (i.e.,PRR dispensing granule, PRRDG) on DVT and explore the underlying mechanism. STUDY DESIGN/METHODS: The chemical profile of PRRDG was analyzed by high-performance liquid chromatography. Sprague-Dawley rats were intragastrically treated with PRRDG (0.625, 1.25 and 1.875 g crude drug/kg/d) once daily for 7 consecutive days. On the sixth day, a model of inferior vena cava (IVC) stenosis-induced DVT was established. All rats were sacrificed on the seventh day. Serum was collected for enzyme-linked immunosorbent assay. Thrombus-containing IVC was weighed and further processed for histopathologic examination, immunohistochemical analysis and western blotting. LiCl and LY294002 were adopted to block and increase the activity of glycogen synthase kinase 3ß (GSK3ß), respectively. RESULTS: The chemical profile analysis showed that paeoniflorin, benzoylpaeoniflorin, albiflorin, gallic acid and catechin were the main constituents of PRRDG. LiCl decreased thrombus weight, reduced the number of inflammatory cells in thrombus and vein wall, down-regulated phosphorylated NF-κB p65 (p-p65) protein expression. Similarly, PRRDG decreased thrombus weight and tissue factor (TF) protein expression. PRRDG reduced the protein expression levels of P-selectin, monocyte chemoattractant protein-1 (MCP-1), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in venous endothelium, serum levels of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß), and the number of inflammatory cells in thrombus and vein wall. Moreover, PRRDG down-regulated p-p65 protein expression and up-regulated phosphorylated GSK3ß (p-GSK3ß) protein expression. LY294002 abrogated the inhibitory effects of PRRDG on thrombus weight, TF protein expression, TNF-α and IL-1ß serum levels, inflammatory cells influxes, and p-p65 protein expression. CONCLUSION: PRRDG prevents DVT by ameliorating inflammation through inhibiting GSK3ß activity.

Medically Ill hospitalized Patients for COVID-19 THrombosis Extended ProphyLaxis with rivaroxaban ThErapy: Rationale and Design of the MICHELLE Trial.

BACKGROUND: The devastating Coronavirus disease (COVID-19) pandemic is associated with a high prothrombotic state. It is unclear if the coagulation abnormalities occur because of the direct effect of SARS-CoV-2 or indirectly by the cytokine storm and endothelial damage or by a combination of mechanisms. There is a clear indication of in-hospital pharmacological thromboprophylaxis for every patient with COVID-19 after bleed risk assessment. However, there is much debate regarding the best dosage regimen, and there is no consensus on the role of extended thromboprophylaxis. DESIGN: This study aims to evaluate the safety and efficacy of rivaroxaban 10 mg once daily for 35 ± 4 days versus no intervention after hospital discharge in COVID-19 patients who were at increased risk for VTE and have received standard parenteral VTE prophylaxis during hospitalization. The composite efficacy endpoint is a combination of symptomatic VTE, VTE-related death, VTE detected by bilateral lower limbs venous duplex scan and computed tomography pulmonary angiogram on day 35 ± 4 posthospital discharge and symptomatic arterial thromboembolism (myocardial infarction, nonhemorrhagic stroke, major adverse limb events, and cardiovascular death) up to day 35 ± 4 posthospital discharge. The key safety outcome is the incidence of major bleeding according to ISTH criteria. SUMMARY: The MICHELLE trial is expected to provide high-quality evidence around the role of extended thromboprophylaxis in COVID-19 and will help guide medical decisions in clinical practice.1.

Alternative physical treatments for deep venous thrombosis prophylaxis in surgical patients: a systematic review.

INTRODUCTION: Venous thromboembolism (VTE) represents a major cause of morbidity and mortality. A variety of novel physical therapies have been proposed for patients in whom standard prophylaxis, including early mobilisation, is contraindicated. This article presents a systematic literature review of alternative physical treatments for VTE prophylaxis, focusing on surgical and trauma patients. METHODS: Following protocol registration in PROSPERO, a systematic review was conducted in accordance with PRISMA. MEDLINE and EMBASE databases were searched for all studies indexed before 27th of July 2019. Two authors independently screened these articles. Data gathering for eligible articles was also undertaken in parallel by two authors. A formal risk of bias assessment was conducted for each study along with an assessment on the quality of the evidence using the GRADE framework. RESULTS: A total of 272 abstracts were identified. After exclusion of duplicates and non-eligible articles, 10 publications were reviewed in detail. Two studies involving electrostimulation, another using a portable intermittent compression device and one study using postoperative calf massage reported a statistically significant reduction in the incidence of deep venous thrombosis when used in conjunction with LMWH. The remaining six articles did not show any significant benefits. DISCUSSION: All studies reporting significant benefits have methodological flaws, with a high risk of bias. The evidence base informing alternative physical treatments as prophylactic measures in VTE is limited. Our data suggest that the use of these physical modalities can be beneficial in patients who also received LMWH, whilst these alone are of no benefit. LEVEL OF EVIDENCE: II - Systematic Review Systematic Review Registration Number PROSPERO CRD42019133684.

Strategy to prevent nerve injury and deep vein thrombosis in radiofrequency segmental thermal ablation of the saphenous veins using a new objective pain scale.

OBJECTIVE: We evaluated the benefit of local anesthesia including tumescent anesthesia and active walking soon after surgery in preventing nerve injury and deep vein thrombosis caused during endovenous ablation. METHODS: Endovenous ablation was performed in 1334 consecutive patients. Varicectomy was performed using the stab avulsion technique. After surgery, patients were encouraged to walk 100-200 m inside the ward for 3-5 times/h. The pain was evaluated objectively using the Okamura pain scale and subjectively using the numerical rating scale. RESULTS: Stab avulsion was performed at 11.8 ± 8.0 sites and the mean operative time was 33.9 ± 15.2 min. The mean Okamura pain scale and numerical rating scale scores were 1.6 ± 1.3 and 3.0 ± 2.0, respectively. Deep vein thrombosis and pulmonary embolism were absent. The incidence of nerve injury was 0.3%. CONCLUSIONS: Endovenous ablation should be performed with the patients under local anesthesia to prevent nerve injury and deep vein thrombosis.

Prevention of Venous Thromboembolism in Acutely Ill Medical Patients: A New Era.

Venous thromboembolism (VTE) is the leading preventable cause of death in hospitalized patients and data consistently show that acutely ill medical patients remain at increased risk for VTE-related morbidity and mortality in the post-hospital discharge period. Prescribing extended thromboprophylaxis for up to 45 days following an acute hospitalization in key patient subgroups that include more than one-quarter of hospitalized medically-ill patients represents a paradigm shift in the way hospital-based physicians think about VTE prevention. Advances in the field of primary thromboprophylaxis in acutely-ill medical patients using validated VTE and bleeding risk assessment models have established key patient subgroups at high risk of VTE and low risk of bleeding that may benefit from both in-hospital and extended thromboprophylaxis. The direct oral anticoagulants betrixaban and rivaroxaban are now U.S. Food and Drug Administration-approved for in-hospital and extended thromboprophylaxis in medically ill patients and provide net clinical benefit in these key subgroups. Coronavirus disease-2019 may predispose patients to VTE due to excessive inflammation, platelet activation, endothelial dysfunction, and hemostasis. The optimum preventive strategy for these patients requires further investigation. This article aims to review the latest concepts in predicting and preventing VTE and discuss the new era of extended thromboprophylaxis in hospitalized medically ill patients.

A botanical medicine dragon's blood exhibited clinical antithrombosis efficacy similar to low molecular weight heparin.

Deep vein thrombosis (DVT) is a common complication following traumatic fracture with a 0.5%-1% annual incidence. Low molecular weight heparin (LMWH) is the most commonly used anticoagulation drug for DVT prevention, but treatment with LMWH is invasive. Our aim is to compare the antithrombotic effect of dragon's blood, an oral botanical anticoagulant medicine approved by the Chinese FDA, with LMWH in patients undergoing hip fracture surgery and to explore the molecular mechanisms of anticoagulation treatment. Our study recruited patients and divided them into LMWH and dragon's blood treatment group. Coagulation index tests, Doppler ultrasound and mRNA sequencing were performed before and after anticoagulation therapy. There was no significant difference in postoperative DVT incidence between the two groups (23.1% versus 15.4%, P=0.694). D-dimer (D-D) and fibrinogen degradation product (FDP) showed significant reductions in both groups after anticoagulation treatments. We identified SLC4A1, PROS1, PRKAR2B and seven other genes as being differentially expressed during anticoagulation therapy in both groups. Genes correlated with coagulation indexes were also identified. Dragon's blood and LMWH showed similar effects on DVT and produced similar gene expression changes in patients undergoing hip fracture surgery, indicating that dragon's blood is a more convenient antithrombosis medicine (oral) than LMWH (hypodermic injection).

The Pharmacology, Efficacy, and Safety of Rivaroxaban in Obese Patient Populations.

Cardiovascular disease (CVD) remains the leading cause of death in the USA. Several risk factors have been identified, and obesity has become one of prominent concern. Excessive weight is considered a risk factor for CVD based on evidence linking it to a hypercoagulable state. Considering the prevalence of CVD and obesity in the USA, along with the increased risk for thrombus-related events, anticoagulation plays a significant role in prevention and treatment. Direct oral anticoagulants have taken the place of many traditional anticoagulants. Considering the recently approved indications and continued postmarketing studies conducted with rivaroxaban, this updated review provides data on the overall impact of obesity on this compound. This includes data obtained from both healthy obese volunteers and obese patients with various CVD conditions enrolled in rivaroxaban clinical trials, along with data obtained from postmarketing real-world evidence studies. Assessment of the clinical pharmacology and population pharmacokinetics in obese individuals revealed no clinically relevant effects of increased weight. Additionally, subgroup analyses from each of the pivotal phase III trials supporting the current approved labeling also demonstrated consistent efficacy and safety results in obese patients. Lastly, these findings are further supported by several recent real-world evidence studies assessing the continued effectiveness and safety of rivaroxaban. In conclusion, rivaroxaban's overall pharmacological and clinical profile remained consistent in obese adults when assessed in both drug development and postmarketing studies, supporting the premise that higher weight does not necessitate adjustment in either dose strength or regimen.

The Preventive Effect of Computed Tomography Image-Guided Electroacupuncture Combined with Continuous Femoral Nerve Block on Deep Vein Thrombosis After Total Knee Arthroplasty Based on an Adaptive Algorithm.

Based on an adaptive algorithm model, this study proposed 2 special model structures of randomized fusion and an optimized convolution kernel and use it for image recognition. The adaptive algorithm model combined image-guided electroacupuncture with a continuous femoral nerve block to prevent deep vein thrombosis after total knee arthroplasty. A total of 200 patients after total knee arthroplasty were randomly divided into 4 groups. We assessed the incidence of postoperative lower limb deep vein thrombosis and platelet count before and after surgery. Electroacupuncture combined with continuous femoral nerve block can reduce the incidence of deep vein thrombosis and has obvious advantages in multimode prevention. The effective analgesia provided by electroacupuncture combined with continuous femoral nerve block relieved postoperative pain. It also enabled patients to participate in joint movement and lower limb muscle strength training as soon as possible, which not only is conducive to postoperative functional recovery, but also reduces the body stress response triggered by pain and the hypercoagulable state. Moreover, electroacupuncture stimulation of electroacupuncture points can reduce the inflammatory edema associated with surgery, improve blood circulation at the surgical site, and activate the body's anticoagulation mechanism. This study provides new ideas and references for formulating multimode prevention and control strategies.

Evaluation of the incidence of bleeding in patients prescribed rivaroxaban for the treatment and prevention of deep vein thrombosis and pulmonary embolism in UK secondary care: an observational cohort study.

OBJECTIVES: To evaluate the short-term (12 weeks) safety and utilisation of rivaroxaban prescribed to new-user adult patients for the treatment of deep vein thrombosis and pulmonary embolism and for the prevention of recurrent deep vein thrombosis and pulmonary embolism in a secondary care setting in England and Wales. DESIGN: An observational cohort study using the technique of Specialist Cohort Event Monitoring. SETTING: The Rivaroxaban Observational Safety Evaluation study was conducted across 87 participating National Health Service secondary care trusts in England and Wales. PARTICIPANTS: 1532 patients treated with rivaroxaban for the prevention and treatment of deep vein thrombosis/pulmonary embolism from September 2013 to January 2016. INTERVENTIONS: Non-interventional postauthorisation safety study of rivaroxaban. PRIMARY AND SECONDARY OUTCOME MEASURES: (1) Risk of major bleeding in gastrointestinal, intracranial, and urogenital sites and (2) risk of all major and clinically relevant non-major bleeds. RESULTS: Of a total of 4846 patients enrolled in the study from September 2013 to January 2016, 1532 were treated with rivaroxaban for the prevention and treatment of deep vein thrombosis/pulmonary embolism. The median age of the deep vein thrombosis/pulmonary embolism cohort was 63 years, and 54.6% were men. The risk of major bleeding within the gastrointestinal, urogenital and intracranial primary sites was 0.7% (n=11), 0.3% (n=5) and 0.1% (n=1), respectively. The risk of major bleeding in all sites was 1.5% (n=23) at a rate of 8.3 events per 100 patient-years. CONCLUSIONS: In terms of the primary outcome risk of major bleeding in gastrointestinal, intracranial and urogenital sites, the risk estimates in the population using rivaroxaban for deep vein thrombosis/pulmonary embolism were low (<1%) and consistent with the risk estimated from clinical trial data and in routine clinical practice. TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov Registry (NCT01871194); ENCePP Registry (EUPAS3979).

Saponins as Modulators of the Blood Coagulation System and Perspectives Regarding Their Use in the Prevention of Venous Thromboembolic Incidents.

Saponins comprise a heterogenous group of chemical compounds containing a triterpene or steroid aglycone group and at least one sugar chain. They exist as secondary metabolites, occurring frequently in dicotyledonous plants and lower marine animals. Plant saponin extracts or single saponins have indicated antiplatelet and anticoagulant activity. Venous thromboembolism (VTE), including deep venous thrombosis and pulmonary embolism, is a multifactorial disease influenced by various patient characteristics such as age, immobility, previous thromboembolism and inherited thrombophilia. This mini-review (1) evaluates the current literature on saponins as modulators of the coagulation system, (2) discusses the impact of chemical structure on the modulation of the coagulation system, which may further provide a basis for drug or supplement design, (3) examines perspectives of their use in the prevention of VTE. It also describes the molecular mechanisms of action of the saponins involved in the prevention of VTE.