Distinct antithrombin activation modes for fondaparinux and natural heparins detected using millisecond hydrogen deuterium exchange and collision induced unfolding.

Low molecular weight heparin and synthetic mimetics such as fondaparinux show different binding kinetics, protease specificity, and clinical effects. A combination of allosteric and template-mediated bridging mechanisms have been proposed to explain the differences in rate acceleration and specificity. The difficulty in working with heterogeneous heparin species has rendered a crystallographic interpretation of the differences in antithrombin activation between mimetics and natural heparin inaccessible. In this study, we examine the allosteric changes in antithrombin caused by binding fondaparinux, enoxaparin and depolymerized natural heparins using millisecond hydrogen deuterium exchange mass spectrometry (TRESI-HDX MS) and relate these conformational changes to complex stability in the gas phase using collision induced unfolding (CIU). This exploration reveals that in addition to the dynamic changes caused by fondaparinux, long chain heparins reduce structural flexibility proximal to Arg393, the cleavable residue in the reactive centre loop of the protein. These local changes in protein dynamics are associated with an increase in overall complex stability that increases with heparin chain length. Ultimately, these results shed light on the molecular mechanisms underlying differences in activity and specificity between heparin mimetics and natural heparins.

A Comparison Between Fondaparinux Sodium and Low-Molecular-Weight Heparin in Preventing Patients Undergoing Hip Replacement from Deep Vein Thrombosis.

OBJECTIVES: Total hip arthroplasty (THA) is a highly successful and effective surgery for improving hip functions and relieving pain. However, the lower extremities are prone to deep vein thrombosis (DVT) and swelling after surgery, thereby delaying recovery. In this study, we investigated the preventive effects of fondaparinux sodium (FS) and low-molecular-weight heparin (LMWH) on DVT of the lower extremity after THA. METHODS: Firstly, 60 patients who underwent THA at the First Affiliated Hospital of Wannan Medical College from March 2020 to December 2020 were included. Next, the patients were randomly divided into an LMWH group (n = 30) and an FS group (n = 30). Then, the indexes related to DVT were compared between both groups. RESULTS: Specifically, the differences in baseline data, such as age, gender and body mass index (BMI), between the two groups were not statistically significant. The postoperative weight bearing time of patients in the FS group was much shorter than that in the LMWH group. CONCLUSION: Subcutaneous injection of FS not only exhibits superior effects to LMWH in preventing DVT after THA but also has a correlation with reducing the risk of thrombosis and improving patient symptoms.

Chemokine Oligomers and the Impact of Fondaparinux Binding.

Heparin, a widely used clinical anticoagulant, is generally well-tolerated; however, approximately 1% of patients develop heparin-induced thrombocytopenia (HIT), a serious side effect. While efforts to understand the role of chemokines in HIT development are ongoing, certain aspects remain less studied, such as the stabilization of chemokine oligomers by heparin. Here, we conducted a combined ion mobility-native mass spectrometry study to investigate the stability of chemokine oligomers and their complexes with fondaparinux, a synthetic heparin analog. Collision-induced dissociation and unfolding experiments provided clarity on the specificity and relevance of chemokine oligomers and their fondaparinux complexes with varying stoichiometries, as well as the stabilizing effects of fondaparinux binding.

Comparison of efficacy of nadroparin and fondaparinux sodium for prevention of deep vein thromboembolism in lower extremities after total hip arthroplasty and total knee arthroplasty: a retrospective study of 592 patients.

OBJECTIVES: To compare the efficacy of nadroparin and fondaparinux sodium for prevention of deep vein thromboembolism (DVT) in lower extremities after total hip arthroplasty (THA) and total knee arthroplasty (TKA). METHODS: A total of 592 patients were enrolled in the study. Clinical data of patients who underwent total hip arthroplasty (THA) and total knee arthroplasty (TKA) in our hospital from December 2021 to September 2022 were retrospectively collected, which mainly included patients' general information, surgery-related information, and DVT-related information. The patients were categorized into the nadroparin group(n = 278) and the fondaparinux sodium group(n = 314) according to the types of anticoagulants used. Anticoagulant therapy began 12-24 h after operation and continued until discharge. DVT prevalence between two groups was compared. The Statistical Package for Social Sciences (SPSS) software version 25 (SPSS, Armonk, NY, USA) was used for statistical analysis. RESULTS: The prevalence of DVT in the nadroparin group and the fondaparinux sodium group was 8.3% (23/278) and 15.0% (47/314), respectively(p = 0.012). Statistical analysis showed that nadroparin group showed a lower prevalence of thrombosis than fondaparinux group (OR = 1.952, P = 0.012). Subgroup analyses showed that nadroparin group had a lower prevalence of DVT than fondaparinux group in some special patients groups such as female patients (OR = 2.258, P = 0.007), patients who are 65-79 years old (OR = 2.796, P = 0.004), patients with hypertension (OR = 2.237, P = 0.042), patients who underwent TKA (OR = 2.091, P = 0.011), and patients who underwent combined spinal-epidural anesthesia (OR = 2.490, P = 0.003) (P < 0.05). CONCLUSION: Nadroparin may have an advantage over fondaparinux sodium in preventing DVT in lower extremities after THA and TKA.

Heparin-induced DRESS syndrome in a paediatric patient and successful anaesthetic management in cardiovascular bypass surgery: case report.

BACKGROUND: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome is a severe adverse drug reaction marked by delayed hypersensitivity reactions causing skin and systemic complications. DRESS diagnosis is challenging due to the variety of clinical presentations and symptom overlap with other conditions. The perioperative period in these patients requires precise pharmacological strategies to prevent complications associated with this syndrome. The treatment of DRESS induced by unfractionated heparin during cardiopulmonary bypass (CPB) surgery presents some challenges that must be considered when selecting an anticoagulant to avoid side effects. In this case, bivalirudin, a direct thrombin inhibitor, is indicated as an alternative to heparin in patients undergoing CPB. However, in contrast to heparin/protamine, there is no direct reversal agent for bivalirudin. CASE PRESENTATION: We report the case of an 11-year-old male diagnosed with native aortic valve endocarditis and thrombosis in his left lower extremity. During valvular replacement surgery, systemic unfractionated heparin was administered. Postoperatively, the patient developed fever, eosinophilia and pruritic rash. Warm shock and elevated alanine transaminase (ALT) and aspartate transaminase (AST) levels followed, leading to the diagnosis of DRESS syndrome. Treatment with methylprednisolone resulted in complete resolution of symptoms. Seven years later, the patient was readmitted due to insufficient anticoagulation and a thrombus in the prosthetic aortic valve, presenting a recurrent DRESS episode due to the administration of unfractionated heparin, which was later replaced with low-molecular-weight heparin during hospitalization. Treatment with corticosteroids and antihistamines was initiated, resulting in the resolution of this episode. Ultimately, the patient required the Ross procedure. During this intervention the anticoagulation strategy was modified, unfractionated heparin was replaced with bivalirudin during the procedure and fondaparinux was administered during the postoperative period. This resulted in stable transaminases levels and no eosinophilia. CONCLUSION: The severity of DRESS Syndrome underscores the importance of early recognition, heightened monitoring, and a comprehensive approach tailored to each patient's needs. This particular case highlights the significance of this approach and may have a substantial clinical impact since it provides alternatives to heparin, such as bivalirudin and fondaparinux, in the anticoagulation strategy of CPB for patients who have a hypersensibility reaction to this medication; thus, enhancing clinical outcomes by minimizing risks linked to adverse drug reactions.

Antithrombotic prophylaxis following total hip arthroplasty: a level I Bayesian network meta-analysis.

BACKGROUND: Several clinical investigations have compared different pharmacologic agents for the prophylaxis of venous thromboembolism (VTE). However, no consensus has been reached. The present investigation compared enoxaparin, fondaparinux, aspirin and non-vitamin K antagonist oral anticoagulants (NOACs) commonly used as prophylaxis following total hip arthroplasty (THA). A Bayesian network meta-analysis was performed, setting as outcomes of interest the rate of deep venous thrombosis (DVT), pulmonary embolism (PE) and major and minor haemorrhages. METHODS: This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension statement for reporting systematic reviews incorporating network meta-analyses of healthcare interventions. All randomised controlled trials (RCTs) comparing two or more drugs used for the prophylaxis of VTE following THA were accessed. PubMed, Web of Science and Google Scholar databases were accessed in March 2023 with no time constraint. RESULTS: Data from 31,705 patients were extracted. Of these, 62% (19,824) were women, with age, sex ratio, and body mass index (BMI) being comparable at baseline. Apixaban 5 mg, fondaparinux, and rivaroxaban 60 mg were the most effective in reducing the rate of DVT. Dabigatran 220 mg, apixaban 5 mg, and aspirin 100 mg were the most effective in reducing the rate of PE. Apixaban 5 mg, ximelagatran 2 mg and aspirin 100 mg were associated with the lowest rate of major haemorrhages, while rivaroxaban 2.5 mg, apixaban 5 mg and enoxaparin 40 mg were associated with the lowest rate of minor haemorrhages. CONCLUSION: Administration of apixaban 5 mg demonstrated the best balance between VTE prevention and haemorrhage control following THA. Level of evidence Level I, network meta-analysis of RCTs.

Fondaparinux Results in Similar Pregnancy Outcomes with Lower Adverse Reaction Rates Compared to Low Molecular Weight Heparin in Chinese Recurrent Miscarriage Women.

Fondaparinux inhibits thrombin generation by inactivating factor Xa, which has the potential to treat recurrent miscarriage (RM). However, more clinical evidence is required to support its application in Chinese women with RM. This research aimed to compare the live birth rate, gestational weeks at delivery, birth weight, Apgar score of newborns, and adverse reaction rates between fondaparinux and low molecular weight heparin (LMWH) in Chinese women with RM. Totally, 132 women with RM treated with fondaparinux or LMWH were included in this retrospective study. According to the corresponding treatment, women with RM were divided into the fondaparinux cohort (N = 45) and LMWH cohort (N = 87). The live birth rate was 68.9% in the fondaparinux cohort and 56.3% in the LMWH cohort, which was not different between the two cohorts (P = 0.161). Multivariable logistics regression analysis suggested that only previous miscarriage times (≥ 4 times vs. < 4 times) were independently related to a lower possibility of live birth in women with RM (odds ratio = 0.431, P = 0.036). It was also observed that gestational weeks at delivery (38.1 ± 1.4 vs. 37.7 ± 1.7 weeks) (P = 0.258), birth weight (2,923.7 ± 355.0 vs. 2,807.8 ± 334.0 g) (P = 0.144), and Apgar score of newborns (9.8 ± 0.5 vs. 9.6 ± 0.8) (P = 0.175) were not different between the fondaparinux cohort and LMWH cohort. Inspiringly, the total adverse reaction rate was reduced in the fondaparinux cohort vs. the LMWH cohort (20.0% vs. 37.9%) (P = 0.036). Fondaparinux results in similar pregnancy outcomes with lower adverse reaction rates compared to LMWH in Chinese women with RM.

Development of a Rapid Qualitative Screen for Anticoagulant Presence.

BACKGROUND: Direct oral anticoagulants (DOACs) and fondaparinux with stable pharmacokinetics are commonly used anticoagulants for outpatient care. Due to the lack of monitoring requirements, drug-specific assays are not available in most hospital laboratories, but drug levels are needed in some urgent/emergency situations. This study describes the development of a qualitative screen for the presence of DOAC or fondaparinux using coagulation tests found in most laboratories. METHODS: The DOAC screen is composed of a heparin anti-Xa activity assay and thrombin time (TT) assay. The STA®-Liquid-Anti-Xa assay calibrated with Stago Multi Hep® and STA®-TT were run on STA-R Max® analyzers. The anti-Xa activity and TT assays were repeated 5 times in samples of commercially available calibrators and controls for each drug: fondaparinux, dabigatran, rivaroxaban, apixaban, and edoxaban. Statistical analysis and correlations were performed for anti-Xa activity and TT results for each drug and pooled normal plasma. RESULTS: A significant correlation was found between heparin-calibrated anti-Xa levels and fondaparinux, rivaroxaban, apixiban, and edoxaban (r2 = 0.99-1.0). Dabigatran showed a strong linear correlation (r2 = 0.99) with TT. Anti-Xa levels >0.3 IU/mL and TT >25 seconds were determined as cutoffs at our lab for the detection of clinically relevant drug levels of factor Xa inhibitor and direct thrombin inhibitor, respectively. CONCLUSIONS: Our study demonstrates that commonly available heparin anti-Xa activity and TT assays can be used to qualitatively detect DOACs and fondaparinux and provides a method to establish a qualitative interpretation.

Synthesis of Anticoagulant Pentasaccharide Fondaparinux via 3,5-Dimethyl-4-(2'-phenylethynylphenyl)phenyl Glycosides.

Here, we disclosed a convenient procedure for the preparation of EPP [3,5-dimethyl-4-(2'-phenylethynylphenyl)phenyl] glycosides and their application to an effective synthesis of fondaparinux, the clinically approved anticoagulant heparin pentasaccharide. The use of EPP glycosides in the one-pot orthogonal glycosylation for the synthesis of heparin-like tetrasaccharides has also been achieved.

The effectiveness of venous thromboembolism prophylaxis interventions in trauma patients: A systematic review and network meta-analysis.

BACKGROUND: Venous thromboembolism (VTE) is a major complication of trauma. Currently, there are few studies summarising the evidence for prophylaxis in trauma settings. This review provides evidence for the use of VTE prophylactic interventions in trauma patients to produce evidence-based guidelines. METHODS: A PRISMA-compliant review was conducted from Sep 2021 to June 2023, using Embase, Medline and Google Scholar. The inclusion criteria were: randomized-controlled trials (RCTs) in English published after 2000 of adult trauma patients comparing VTE prophylaxis interventions, with a sample size higher than 20. The network analysis was conducted using RStudio. The results of the pairwise comparisons were presented in the form of a league table. The quality of evidence and heterogeneity sensitivity were assessed. The primary outcome focused on venous thromboembolism (VTE), and examined deep vein thrombosis (DVT) and pulmonary embolism (PE) as separate entities. The secondary outcomes included assessments of bleeding and mortality. PROSPERO registration: CRD42021266393. RESULTS: Of the 7,948 search results, 23 studies with a total of 21,312 participants fulfilled screening criteria, which included orthopaedic, spine, solid organ, brain, spinal cord, and multi-region trauma. Of the eight papers comparing chemical prophylaxis medications in patients with hip or lower limb injuries, fondaparinux and enoxaparin were found to be significantly superior to placebo in respect of prevention of DVT, with no increased risk of bleeding. Regarding mechanical prophylaxis, meta-analysis of two studies of inferior vena cava filters failed to provide significant benefits to major trauma patients. CONCLUSION: Enoxaparin and fondaparinux are safe and effective options for VTE prevention in trauma patients, with fondaparinux being a cheaper and easier administration option between the two. Inconclusive results were found in mechanical prophylaxis, requiring more larger-scale RCTs.

Monitoring the appropriate prescription of low molecular weight heparins and Fondaparinux through administrative data. A retrospective observational study in the Tuscany region.

INTRODUCTION: Low Molecular Weight Heparins (LMWHs) and Fondaparinux have been widely used as anticoagulants. Mass prescription may lead to prescriptive inappropriateness, which causes Heparin-induced thrombocytopenia and other side effects. OBJECTIVES: The study investigates the appropriate prescription of LMWHs and Fondaparinux in Tuscany. We aim to validate the crude measure of prescription appropriateness of the Key Performance Indicator (KPI) "Patients treated with LMWHs and Fondaparinux every hundred residents in Tuscany" as a proxy for monitoring prescription appropriateness. METHODS: To compare a crude KPI based only on drug consumption with a refined KPI based on exclusions listed in the clinical guidelines, a retrospective observational cohort study was carried out, using the RECORD guidelines for the year 2019. The refined indicator is computed via record linkage of different datasets regarding (a) pharmaceutical services; (b) hospital discharge records; (c) outpatient services; and (d) birth certificates. We apply exclusion criteria to identify the cohort of patients. Values of the KPI are compared, by ranking, with those obtained from its refined version. A Spearman test was performed to validate the use of the crude KPI as a proxy. RESULTS: 208,717 LMWH and Fondaparinux users are identified, of which 103,299 fall within the study's inclusion criteria. 16,817 (16%) of LMWHs and Fondaparinux users are classified as high consumption. The refined version of the KPI produces the same ranking results in terms of local health districts (rho = 0.98 p<0.01). CONCLUSIONS: Although the crude KPI is less refined and detailed than the adjusted indicator computed by our study, it has proven capable to provide an accurate snapshot of the use of these drugs across the region. This analysis is useful to enable regional and local managers to run rapid and simple indicators to monitor the appropriateness of LMWHs and Fondaparinux. This analysis should be reviewed periodically to confirm its accuracy.

Determinants of Late Venous Thromboembolic Events After Acute Isolated Superficial Vein Thrombosis in Daily Practice: 12 Month Results of the INSIGHTS-SVT Study.

OBJECTIVE: Long term incidence of symptomatic venous thromboembolism (VTE) and bleeding events in patients with superficial vein thrombosis (SVT) was investigated. METHODS: In this prospective, observational study, patients with acute SVT were treated at the discretion of the responsible physician. The primary efficacy outcome was symptomatic VTE including deep vein thrombosis (DVT), pulmonary embolism (PE), and recurrent or extending SVT. The primary safety outcome was clinically relevant bleeding, recorded at periodic clinic visits over a 12 month period. RESULTS: The mean age of 872 patients with 12 month follow up was 60.6 ± 14.5 years, 64.5% were female, 80.1% had chronic venous disease (defined as chronic venous insufficiency and or varicose veins), and 41.9% had a history of VTE. They were receiving fondaparinux in 62.1% (mean duration 34.9 ± 15.7 days), low molecular weight heparin (LMWH) in 25.0% (mean duration 26.2 ± 23.2 days), any other anticoagulants in 6.2%, and no anticoagulant in 6.7%. At 12 months, 108 patients (14.3%) achieved the primary efficacy outcome. The most common VTE event was recurrent or extending SVT in 11.0%, followed by symptomatic DVT in 2.7%, symptomatic PE in 2.4%, hospitalisation due to VTE in 1.8%, and death in 1.1%. Clinically relevant bleeding events occurred in 2.1% of patients, and major bleedings in 0.3%. By drug, the rate of the primary efficacy outcome was highest in the LMWH group (22.4%) and lowest in the fondaparinux group (10.4%). In a multivariable model, patients with events between three months and 12 months were significantly more likely to have higher BMI (hazard ratio [HR] 1.06; p = .002), history of VTE (HR 2.89; p = .002), and severe systemic infections (HR 7.59; p = .006). CONCLUSION: The risk of symptomatic VTE remained elevated over 12 months of follow up. Therefore, anticoagulation beyond 45 days may be considered in patients with risk factors. [ClinicalTrials.gov identifier: NCT02699151.].

Comparison of the efficacy of low-molecular-weight heparin and fondaparinux sodium after total knee arthroplasty: a retrospective cohort study.

BACKGROUND: Low-molecular-weight heparin (LMWH) and fondaparinux sodium (FPX) are routinely used to prevent deep vein thrombosis (DVT) after total knee arthroplasty (TKA). In this study, we compared the effects of these agents in preventing post-TKA DVT. METHODS: Clinical data of patients who underwent unilateral TKA for unicompartmental knee osteoarthritis at the Ningxia Medical University General Hospital between September 2021 and June 2022 were retrospectively analyzed. Based on the anticoagulation agent used, the patients were divided into LMWH and FPX groups (34 and 37 patients, respectively). Changes in perioperative coagulation-related indicators, d-dimer and platelet count, perioperative complete blood count, amount of blood loss, lower-limb DVT, pulmonary embolism, and allogeneic blood transfusion were determined. RESULTS: Intergroup differences in d-dimer or fibrinogen (FBG) levels before and 1 or 3 days after surgery were not significant (all p > 0.05); within-group pairwise comparisons indicated significant differences (all, p < 0.05). Intergroup differences in preoperative prothrombin time (PT), thrombin time, activated partial PT, and international normalized ratio were not significant (all p > 0.05), whereas significant differences were detected on postoperative days 1 and 3 (all p < 0.05). Intergroup differences in platelet counts before and 1 or 3 days after surgery were not significantly different (all p > 0.05). Pairwise comparisons of hemoglobin and hematocrit levels between patients in the same group before and 1 or 3 days after surgery revealed significant differences in both groups (all p < 0.05); however, intergroup differences were not significant (all p > 0.05). Although intergroup differences in visual analog scale (VAS) scores before and 1 or 3 days after surgery were not significant (p > 0.05), we detected significant intragroup differences in VAS scores before and 1 or 3 days after surgery (p < 0.05). The treatment cost ratio was significantly lower in the LMWH group than in the FPX group (p < 0.05). CONCLUSION: Both LMWH and FPX can effectively prevent DVT after TKA. There are some suggestive signals that FPX may have more beneficial pharmacological effects and clinical significance, while LMWH is cheaper and therefore more economical.

Pregnancy outcomes and adverse events in patients with recurrent miscarriage receiving fondaparinux versus low molecular-weight heparin: A meta-analysis.

OBJECTIVE: Current opinion on the superiority of fondaparinux versus low molecular-weight heparin (LMWH) in treating recurrent miscarriage is controversial. This meta-analysis aimed to comprehensively compare the pregnancy outcomes and adverse events in patients with recurrent miscarriage receiving fondaparinux versus LMWH. METHODS: EMBASE, PubMed, Cochrane, China National Knowledge Internet (CNKI), Wanfang Database, and China Science and Technology Journal Database (CQVIP) databases were searched for articles reporting fondaparinux versus LMWH in treating recurrent miscarriage till June 10, 2022. Inclusion criteria for study screening were: (i) randomized, controlled trials (RCT), non-randomized controlled studies, or observational studies; (ii) patients aged over 18 years; (iii) patients with recurrent miscarriage during gestation period; (iv) patients in the experimental/observational group who received FD, and patients in the control group who received LMWH; (v) studies involving at least one outcome of interest for the current analysis. Exclusion criteria were: (i) systematic reviews, meta-analyses, case reports, or animal studies; (ii) duplicated studies; (iii) incomplete or inconsistent data. Quality assessment was conducted with Newcastle-Ottawa Scale criteria or Cochrane Collaboration. Data of live birth, abortion, birth weight, fetal growth restriction (FGR), and adverse events were extracted and synthesized. RESULTS: Six eligible studies (4 observational studies and 2 RCTs) with 321 patients receiving fondaparinux and 546 patients receiving LMWH were enrolled. Live birth (relative risks (RR) = 1.05, 95% confidence interval (CI) = 0.97 âˆ¼ 1.14, P = 0.217), abortion (RR = 0.73, 95% CI = 0.50 âˆ¼ 1.08, P = 0.113), birth weight (weighted mean difference = 167.20, 95% CI = -236.89 âˆ¼ 571.30, P = 0.417), and FGR (RR = 0.95, 95% CI = 0.25 âˆ¼ 3.59, P = 0.942) were of no difference between patients receiving fondaparinux and LMWH. Regarding adverse events, the incidence of ecchymosis (RR = 0.11, 95% CI = 0.03 âˆ¼ 0.46, P = 0.002) and skin reaction at injection site (RR = 0.15 95% CI = 0.05 âˆ¼ 0.44, P = 0.001) were lower in patients receiving fondaparinux compared with those receiving LMWH, while that of thrombocytopenia (RR = 0.45, 95% CI = 0.09 âˆ¼ 2.14, P = 0.315), vagina bleeding (RR = 1.03, 95% CI = 0.62 âˆ¼ 1.71, P = 0.646), and oral mucosa hemorrhage (RR = 1.08, 95% CI = 0.33 âˆ¼ 3.51, P = 0.899) did not vary between these patients receiving these two treatments. However, most studies were conducted in China, which could induce regional and ethnic bias. CONCLUSION: Fondaparinux is attributable to fewer adverse events and similar pregnancy outcomes compared with LMWH in patients with recurrent miscarriage.

Common Practice in the Treatment of Superficial Vein Thrombosis Involving the Sapheno-Femoral Junction: Results from a National Survey of the Italian Society of Angiology and Vascular Medicine (SIAPAV).

Background and Objectives: Prophylactic doses of low-molecular-weight heparins or fondaparinux showed their efficacy and safety for treatment of all superficial vein thrombosis (SVT) of the lower limbs, yet not for those extended to the last 3 cm of the great saphenous vein, close to the sapheno-femoral junction, or considered as a deep-vein thrombosis. Some experts suggest that these patients should be managed with full anticoagulant doses but evidence to support this recommendation is lacking, suggesting the need for a properly designed trial. Materials and Methods: Before starting a new trial, the Italian Society of Angiology and Vascular Medicine (SIAPAV) decided to verify the common therapeutic approaches for patients with an SVT in Italian vascular centers based on a hypothetical significant variation in each daily clinical practice. A standardized questionnaire of 10 questions was administered to all SIAPAV affiliates by means of the official Society website. Results: From 1 December 2022 to 20 January 2023 a total of 191 members (31.8%) answered the questionnaire, showing a detailed and a substantial heterogeneity in the therapeutic approach to SVT patients among experienced vascular physicians and angiologists. Detailed results are reported in the relative section. Conclusions: The therapeutic approach of SVT extended to the iuxta-femoral segment of the great saphenous vein is still a matter of debate, and data to support therapeutic strategies are lacking. The wide heterogeneity in the management of SVT patients, including those with more extended thrombosis, confirmed that a randomized controlled clinical trial investigating the efficacy and the safety of a tailored therapeutic regimen in this particular subgroup of patients is strongly warranted.

Glycosaminoglycan-directed cobalt complexes.

The biological activity of the 6+ Co containing Werner's Complex has been described and mechanistic considerations suggest that the highly anionic glycosaminoglycans (heparan sulfate, HS, GAGs) are implicated in this activity [Paiva et al. 2021]. To examine in detail the molecular basis of Werner's Complex biological properties we have examined a selection of simple mononuclear Co3+ compounds for their interactions with HS and Fondaparinux (FPX). FPX is a highly sulfated synthetic pentasaccharide used as a model HS substrate [Mangrum et al. 2014, Peterson et al. 2017]. The Co complexes were chosen to be formally substitution-inert and/or have the potential for covalent binding to the biomolecule. Using both indirect competitive inhibition assays and direct mass spectrometric assays, formally substitution-inert complexes bound to FPX with protection from multiple sulfate loss in the gas phase through metalloshielding. Covalent binding of Co-Cl complexes as in [CoCl(NH3)5]2+ and cis-[CoCl2(en)2]+ was confirmed by mass spectrometry. Interestingly, the former complex was shown to be an effective inhibitor of bacterial heparinase enzyme activity and to inhibit heparanase-dependent cellular invasion through the extracellular matrix (ECM). Pursuing the theme of metalloglycomics, we have observed the hitherto unappreciated biological activity of the simple [CoCl(NH3)5]2+ compound, a staple of most inorganic chemistry lab curricula.

Occurrence rates and risk factors of in-hospital venous thromboembolism, major bleeding, and death in patients receiving fondaparinux after orthopedic surgery or trauma surgery.

AIM: Fondaparinux is a synthetic anticoagulant that inhibits thrombosis by suppressing factor Xa. The efficacy of fondaparinux for orthopedic surgeries has been revealed by several foreign studies; however, relevant evidence in Chinese patients is lacking. This study intended to investigate the occurrence rate and risk factors of in-hospital venous thromboembolism (VTE), major bleeding, and death in patients receiving fondaparinux after orthopedic surgery or trauma surgery. METHODS: Totally, 1258 patients who received fondaparinux after orthopedic surgery or trauma surgery were retrospectively enrolled. Meanwhile, in-hospital VTE, major bleeding, and death were obtained for assessment. Besides, adverse events were recorded. RESULTS: The occurrence rates of in-hospital VTE, major bleeding, and death were 2.5%, 21.8%, and 0.0%, respectively. The multivariate logistic regression analysis revealed that only age (> 60 years vs. ≤ 60 years) (odd ratios (OR) = 3.380, P = 0.013) was independently correlated with increased risk of in-hospital VTE. Additionally, osteoarthritis diagnosis (OR = 3.826, P < 0.001), femoral head necrosis diagnosis (OR = 1.809, P = 0.034), hip replacement (vs. internal fracture fixation) (OR = 2.199, P = 0.007), knee replacement (vs. internal fracture fixation) (OR = 2.781, P = 0.002), and serum creatinine (abnormal vs. normal) (OR = 1.677, P = 0.012) were independently linked to a higher risk of in-hospital major bleeding. Moreover, the common adverse events included pain (56.6%), wound bleeding (23.0%), increased drainage (5.2%), etc. CONCLUSION: Fondaparinux realizes low occurrence rates of in-hospital VTE and major bleeding with tolerable adverse events in patients receiving orthopedic surgery or trauma surgery.

Efficacy of 11 anticoagulants for the prevention of venous thromboembolism after total hip or knee arthroplasty: A systematic review and network meta-analysis.

BACKGROUND: To systematically review the efficacy of 11 anticoagulants in the treatment of venous thromboembolism (VTE) after total hip or knee arthroplasty. METHODS: PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang Data, VIP, and China Biology Medicine databases were electronically searched for studies assessing the efficacy of different anticoagulants for the prevention of VTE after total hip or knee arthroplasty from January 1, 2010, to January 27, 2022. Two reviewers independently screened the literature, extracted data, and graded the evidence using Confidence in Network Meta-Analysis. The network meta-analysis was then performed using Stata 16.0 software and R 4.1.0 software. RESULTS: A total of 61 articles were included. The results of network meta-analysis showed that apixaban, edoxaban, fondaparinux, rivaroxaban, and darexaban were the most effective anticoagulants for the prevention of deep vein thrombosis in patients undergoing total hip or knee arthroplasty (P < .05), while there was no difference in the efficacy among the anticoagulants for the prevention of pulmonary embolism (P > .05). CONCLUSION: Apixaban, edoxaban, fondaparinux, rivaroxaban, and darexaban have the best efficacy for the prevention of VTE after total hip or knee arthroplasty.