Influence of Anticoagulants and Heparin Contaminants on the Suitability of MMP-9 as a Blood-Derived Biomarker.

In contrast to other common anticoagulants such as citrate and low-molecular-weight heparin (LMWH), high-molecular-weight heparin (HMWH) induces the expression of matrix metalloproteinase (MMP)-9, which is also measured as a biomarker for stroke in blood samples. Mechanistically, HMWH-stimulated T cells produce cytokines that induce monocytic MMP-9 expression. Here, the influence of further anticoagulants (Fondaparinux, Hirudin, and Alteplase) and the heparin-contaminating glycosaminoglycans (GAG) hyaluronic acid (HA), dermatan sulfate (DS), chondroitin sulfate (CS), and over-sulfated CS (OSCS) on MMP-9 was analyzed to assess its suitability as a biomarker under various conditions. Therefore, starved Jurkat T cells were stimulated with anticoagulants/contaminants. Subsequently, starved monocytic THP-1 cells were incubated with the conditioned Jurkat supernatant, and MMP-9 mRNA levels were monitored (quantitative (q)PCR). Jurkat-derived mediators secreted in response to anticoagulants/contaminants were also assessed (proteome profiler array). The supernatants of HMWH-, Hirudin-, CS-, and OSCS-treated Jurkat cells comprised combinations of activating mediators and led to a significant (in the case of OSCS, dramatic) MMP-9 induction in THP-1. HA induced MMP-9 only in high concentrations, while LMWH, Fondaparinux, Alteplase, and DS had no effect. This indicates that depending on molecular weight and charge (but independent of anticoagulant activity), anticoagulants/contaminants provoke the expression of T-cell-derived cytokines/chemokines that induce monocytic MMP-9 expression, thus potentially impairing the diagnostic validity of MMP-9.

Unresolved questions on venous thromboembolic disease. Therapeutic management of superficial vein thrombosis (SVT). Consensus statement of the French Society for Vascular Medicine (SFMV).

Superficial vein thrombosis (SVT), a manifestation of venous thromboembolism (VTE), is a common condition, yet of all the types of VTE, it has been the least well studied. Recent studies have challenged the conception that SVT is a benign disease, showing that its risk factors overlap with those of deep-vein thrombosis (DVT) and that it is frequently associated with DVT or pulmonary embolism (PE). In 2010, the CALISTO trial demonstrated the benefit of treatment with fondaparinux at the dose of 2.5mg (one injection per day) for 45days for lower limb SVT. Prior to CALISTO, the treatment of SVT was based on venous compression therapy, nonsteroidal anti-inflammatory drugs (NSAID) and anticoagulation using various therapeutic regimens. Surgery could also be envisaged in certain cases. In CALISTO, the inclusion criteria designed to obtain a homogeneous population meant that numerous questions remained unanswered with respect to SVT occurring in other locations and under other circumstances, notably in pregnant women, patients with renal insufficiency, and patients with recurrent SVT or superficial vein thrombosis less than 5cm long. The aim of this section is to review the current state of knowledge of SVT and to propose or recommend therapeutic strategies for the management of SVT according to the clinical context, the location of the thrombosis, and the presence of particular risk factors.

Fondaparinux versus Enoxaparin in the Treatment of Obese Patients with Acute Coronary Syndrome. / Fondaparinux versus Enoxaparina no Tratamento de Pacientes Obesos com Síndrome Coronariana Aguda.

BACKGROUND: Fondaparinux is an effective and safe anticoagulant in the treatment of acute coronary syndromes (ACS). However, due to the low representation of obese individuals in clinical trials, the effects of applying the results of this drug to this population remain uncertain. OBJECTIVES: To compare Fondaparinux to Enoxaparin in the treatment of obese patients with ACS. METHODS: This is a retrospective cohort study, including obese individuals (BMI ≥ 30 Kg/m2) admitted with non-ST-segment elevation myocardial infarction (NSTEMI) or unstable angina (UA) and treated with Fondaparinux or Enoxaparin between 2010 and 2020. The Fondaparinux and Enoxaparin groups were compared for their clinical and laboratory characteristics using chi-square and Mann-Whitney tests, as appropriate. The incidence of primary outcomes (death, reinfarction, stroke, major bleeding) was compared between groups. P-value < 0.05 was considered significant for all analyses. RESULTS: A total of 367 obese patients with NSTEMI or UA were included, of whom 258 used Fondaparinux and 109 used Enoxaparin. Mean age was 64 ± 12 years, and 52.9% were male. The prevalence of diabetes, hypertension, dyslipidemia, prior coronary artery disease, prior stroke, and implementation of invasive strategy was similar between groups. The incidence of the primary outcome was 4.7% in the Fondaparinux group and 5.5% in the Enoxaparin group (p = 0.729). There was no difference between groups when analyzing the components of the primary outcome separately. CONCLUSION: In a sample of obese patients with NSTEMI or UA, there was no difference in the occurrence of the composite outcome (death, stroke, reinfarction, major bleeding) between patients who used Fondaparinux or Enoxaparin.

FUNDAMENTO: O fondaparinux é um anticoagulante eficaz e seguro usado no tratamento de síndromes coronarianas agudas (SCAs). No entanto, devido à baixa representatividade de indivíduos obesos em ensaios clínicos, os efeitos de se aplicar os resultados desse medicamento nesta população continuam incertos. OBJETIVOS: Comparar o fondaparinux à enoxaparina no tratamento de obesos com SCA. MÉTODOS: Este é um estudo do tipo coorte retrospectivo, incluindo indivíduos obesos (IMC ≥ 30 Kg/m2) internados com Infarto do Miocárdio sem Elevação do Segmento ST (IAMSSST) ou Angina Instável (AI) e tratados com fondaparinux ou enoxaparina entre 2010 e 2020. Os grupos que receberam fondaparinux e enoxaparina foram comparados quanto suas características clínicas e laboratoriais usando o teste do qui-quadrado e o teste de Mann-Whitney, conforme apropriado. A incidência dos desfechos primários (morte, reinfarto, acidente vascular cerebral, sangramento maior) foi comparada entre os grupos. Um p<0,05 foi considerado estatisticamente significativo em todas as análises. RESULTADOS: Um total de 367 pacientes obesos com IAMSSST ou AI foi incluído, dos quais 258 usaram fondaparinux e 109 usaram enoxaparina. A idade média foi 64 ± 12 anos, 52,9% eram do sexo masculino. A prevalência e diabetes, hipertensão, dislipidemia, doença arterial coronariana prévia, acidente vascular cerebral prévio, e implementação de estratégia invasiva foi similar entre os grupos. A incidência do desfecho primário foi 4,7% no grupo fondaparinux e 5,5% no grupo enoxaparina (p = 0,729). Não houve diferença entre os grupos quando os componentes do desfecho primário foram analisados separadamente. CONCLUSÃO: Em uma amostra de pacientes obesos com IAMSSST ou AI, não houve diferença na ocorrência do desfecho composto (morte, acidente vascular cerebral, reinfarto, sangramento maior) entre os pacientes que utilizaram fondaparinux ou enoxaparina.

Fondaparinux Sodium for Anticoagulant Therapy After Primary Percutaneous Coronary Intervention: A Single-Center Randomized Trial in China.

ABSTRACT: In this study, we investigated the safety and efficacy of fondaparinux sodium in postpercutaneous coronary intervention (PCI) anticoagulation therapy for patients with ST-segment elevation myocardial infarction. There are a total of 200 patients with ST segment elevation myocardial infarction underwent PCI and anticoagulation therapy. They were randomly split into experimental (n = 108) and control groups (n = 92). The experimental group received postoperative fondaparinux sodium (2.5 mg q.d), while the control group received enoxaparin (4000 IU q12 h). We did not use a loading dose for enoxaparin. Bleeding incidence and major adverse cardiovascular/cerebrovascular events were monitored during hospitalization, and at 1, 3, and 6 months postsurgery. The primary end points, including bleeding, mortality, and myocardial infarction during hospitalization, were not significantly different between the 2 groups. For secondary end points, the incidence of combined end point events at 1 month, 3 months, and 6 months after surgery in the experimental group was lower than in the control group (P < 0.05). According to Cox regression analysis, the risk of bleeding in the experimental group was significantly lower than that in the control group [hazard ratios: 0.506, 95% confidence interval (CI): 0.284-0.900] (P = 0.020). The risk of mortality in the experimental group was significantly lower than in the control group (hazard ratio: 0.188, 95% CI: 0.040-0.889) (P = 0.035). In summary, perioperative use of fondaparinux sodium during PCI in patients with STEMI in this study was associated with a lower risk of bleeding and death compared with enoxaparin use in the absence of loading dose.

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

INTRODUCTION: Venous thromboembolism (VTE) is a major concern following total knee arthroplasty (TKA). The optimal pharmacological prophylaxis remains, however, controversial. The present investigation compared several non-vitamin K antagonist oral anticoagulants commonly employed as VTE prophylaxis following TKA. A Bayesian network meta-analysis was conducted to compare apixaban, aspirin, dabigatran, edoxaban, enoxaparin, fondaparinux, and rivaroxaban. The outcomes of interest were to compare the rate of deep venous thrombosis (DVT), pulmonary embolism (PE), and major and minor haemorrhages. METHODS: This study was conducted according to the PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-Analyses of Health Care Interventions. In March 2024, PubMed, Web of Science, and Google Scholar were accessed with no time constraints. All randomised controlled trials (RCTs) comparing two or more drugs for the prevention of VTE following TKA were considered for inclusion. RESULTS: Data from 29,678 patients were collected. Of them, 67% (19,884 of 29,678 patients) were women. The mean age of the patients was 66.8 ± 2.8 years, and the mean BMI was 29.2 ± 1.5 kg/m2. There was comparability in age, sex, and BMI at baseline. Apixaban 5 mg, dabigatran 220 mg, and rivaroxaban 10 mg were the most effective in reducing the rate of DVT. Apixaban 5 mg, enoxaparin 60 mg, and rivaroxaban 40 mg were the most effective in reducing the rate of PE. Apixaban 5 mg, rivaroxaban 10 mg, and apixaban 10 mg were associated with the lowest rate of major haemorrhages. Apixaban 5 mg and 20 mg, and dabigatran 220 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 TKA. LEVEL OF EVIDENCE: Level I, network meta-analysis of RCTs.

Anticoagulants for the treatment of isolated lower limb superficial vein thrombosis a Bayesian network meta-analysis of randomized controlled trials.

OBJECTIVE: Assess the safety and efficacy of anticoagulants in treating isolated superficial vein thrombosis (iSVT). MATERIALS AND METHODS: A systematic review was conducted according to PRISMA 2020 guidelines, for randomized controlled trials (RCTs) investigating anticoagulants in the treatment of iSVT. The primary endpoint of thrombotic complications encompassed any incident of iSVT progression/recurrence and the development of new-onset (deep vein thrombosis) DVT or (pulmonary embolism) PE. RESULTS: Eight RCT's and 4721 patients treated once daily with either fondaparinux 2.5 mg, rivaroxaban 10 mg, therapeutic, intermediate, and prophylactic low molecular weight heparin (LMW) were included. While all anticoagulants displayed a statistically significant risk reduction compared to placebo in terms of thrombotic complications and iSVT progression/recurrence, only fondaparinux reduced the risk for DVT/PE. Additionally, fondaparinux exhibited enhanced efficacy in decreasing DVT/PE events relative to prophylactic and therapeutic LMWH. Furthermore, rivaroxaban and fondaparinux demonstrated superior outcomes in terms of preventing thrombotic complications compared to all three dosing regimens of LMWH without significant differences between the two, risk ratio RR 1.00(95%CI:0.51-1.92). SUCRA identified fondaparinux as the most effective treatment regarding thrombotic complications, (SUCRA,91.6) and DVT/PE, (SUCRA,96) and rivaroxaban in terms of iSVT progression/recurrence (SUCRA,94.68). Ultimately and despite certain model limitations, meta-regression analysis suggested a possible trend towards improved outcomes with longer treatment durations for thrombotic complications ß = -0.34(95%CI:-16.39to12.23). CONCLUSIONS: Despite inherent limitations such as variations in treatment durations and follow-up periods, this review displayed the efficacy of fondaparinux, rivaroxaban and LMWH in treating iSVT. The improved efficacy of fondaparinux over therapeutic LMWH in terms of DVT/PE outcomes necessitates cautious interpretation underscoring the need for further investigation through adequately powered RCTs.

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.

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.

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.].