Fingerprinting analyses of low molecular weight heparin with an orthogonal MHC 2D LC-MS system.

In this work, a synthetical glycan fingerprinting strategy using a multiple heart-cut two-dimensional liquid chromatography system linked to mass spectrometry (MHC 2D LC-MS) was developed to analyze enoxaparin, a widely used low molecular weight heparin (LMWH). Glycans from an enoxaparin standard were prepared offline based on size, and the derived tetra-, hexa-, octa- and decasaccharides were profiled using a qualitative analytical platform. Strong anion exchange chromatography (SAX) was employed as the first-dimensional chromatography (1D) to separate glycans of the same size but with different charges or sequences, while size exclusion chromatography (SEC) was used in the second dimension (2D) for desalting before MS analysis. The retention times (RTs), accurate masses and structural compositions of the glycans were fully characterized. Real samples were analyzed using the same platform but with 1D and 2D exchanged: SEC was used to separate enoxaparin glycans by size, followed by SAX using the same parameters as in the qualitative platform to separate glycans by charge or sequence. Glycans in real samples were identified by matching their RTs to those assigned in the qualitative analysis and semi-quantitated after normalization of peaks in each SAX chromatogram of glycans of different sizes. The analyses were performed automatically and robustly using this synthetical platform, enabling the fingerprinting and differentiation of enoxaparins from various sources. This platform could serve as a powerful tool for structural analysis, quality control, and heparin-related drug development.

Predictors of recurrent venous thromboembolism and major bleeding in patients with cancer: A secondary analysis of the CANVAS trial.

INTRODUCTION: Patients with cancer have an increased risk of developing venous thromboembolism (VTE) but also have an increased risk of both recurrent VTE and bleeding with anticoagulation compared to anticoagulated patients without cancer. CANVAS, a randomized pragmatic effectiveness trial, compared the direct oral anticoagulants a class to low molecular weight heparin for treatment of a new VTE in patients with cancer. The aim of this prespecified secondary analysis of the CANVAS trial is to identify predictors of both recurrent VTE and major bleeding in patients with cancer and new VTE. METHODS: Data from the 671 participants in the analysis population were used to identify predictors of recurrent VTE and bleeding during the 6-month treatment period. Significant predictors identified in the univariable models were carried forward in the multivariable models to identify independent predictors of both risks. RESULTS: Independent predictors of recurrent VTE include ECOG performance status ≥2 (HR, 3.19 [95 % CI, 1.45-7.02]; P < .005), presence of metastatic disease (HR, 2.57 [95 % CI, 1.14-5.80]; P = .023), treatment with bevacizumab (HR, 2.50 [95 % CI, 1.04-5.99]; P = .041), and deep vein thrombosis without pulmonary embolus as index VTE (HR, 1.86 [95 % CI, 1.04-3.33]; P = .037). Independent predictors of major bleeding include serum albumin <3.5 g/dL (HR 1.97 [95 % CI, 1.02-3.79]; P = .044) and metastatic disease (HR 2.80 [95 % CI, 1.08-7.22]; P = .034). CONCLUSION: Findings from this pre-specified analysis of the CANVAS trial identified risk factors for recurrent VTE and major bleeding in a population of participants with cancer and new VTE that reflect current oncology clinical practice. Results can be used to identify at risk patients in practice and inform new risk prediction models to improve the care of these patients.

Incidence and Predictors of Early and Late Radial Artery Occlusion after Percutaneous Coronary Intervention and Coronary Angiography: A Systematic Review and Meta-Analysis.

Introduction: Trans-radial access for coronary angiography and percutaneous coronary intervention (PCI) has gained popularity due to its advantages over the traditional transfemoral approach. However, radial artery occlusion (RAO) remains a common complication following trans-radial procedures. This study aimed to investigate the incidence of early and late RAO along with their risk factors. Methods: Six databases, Medline (Ovid), National Library of Medicine (MeSH), Cochrane Database of Systematic Reviews (Wiley), Embase, Scopus, and Global Index Medicus, were searched. The systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data were extracted and analyzed. Using a random-effect model, the primary endpoint was the overall incidence of RAO after invasive coronary procedures. Subgroup analysis and meta-regression were also performed to identify possible predictors of RAO. Results: A total of 41 studies with 30,020 patients were included. The overall incidence of RAO was 13% (95% CI = 0.09-0.16). The incidence of early RAO (within 24 h) was 14% (95% CI = 0.10-0.18) in 26 studies, while the incidence of late RAO (after 24 h) was 10% (95% CI = 0.04-0.16) in 22 studies. The average incidence rates of early RAO in studies with catheter sizes of <6 Fr, 6 Fr, and >6 Fr were 9.8%, 9.4%, and 8.8%. The overall effect size of female gender as a predictor was 0.22 with a 95% CI of 0.00-0.44. Age was a potential predictor of early RAO (B = 0.000357; 95% CI = -0.015-0.0027, p: 0.006). Conclusions: This meta-analysis provides essential information on the incidence of early (14%) and late (10%) RAO following angiographic procedures. Additionally, our findings suggest that female sex and age are possible predictors of RAO. A larger catheter, especially (6 Fr) and hemostatic compression time <90 min post-procedure, substantially reduced the incidence of RAO. The use of oral anticoagulation and the appropriate dosage of low-molecular-weight heparin (LMWH) does reduce RAO, but a comparison between them showed no statistical significance.

Effect of Low Molecular Weight Heparin Calcium on Prevention of Lower Limb Deep Venous Thrombosis in Oral Cancer Patients With Anterolateral Thigh Flap Reconstruction.

BACKGROUND: This study aimed to evaluate the effect of low molecular weight heparin calcium (LMWH-Ca) on the prevention of deep venous thrombosis (DVT) in patients with anterolateral thigh (ALT) flap reconstruction. METHODS: In total, 1001 patients with oral cancer who underwent ALT flap reconstruction were recruited. Based on the postoperative use of LMWH-Ca, the patients were divided into case (n = 633) and control groups (n = 368). The incidence of postoperative DVT was compared between groups. RESULTS: There was no significant difference in DVT incidence between the two groups. Among patients older than 60 years, the incidence of lower limb DVT in the case group (0.813%) was significantly lower than that in the control group (8.108%, p = 0.012). CONCLUSION: The postoperative use of LMWH in oral cancer patients with ALT flap transfer does not prevent the development of lower limb DVT. However, patients older than 60 years old benefited from the postoperative use of LMWH-Ca.

Cost-effectiveness analysis of direct oral anticoagulants versus low-molecular-weight heparin and no thromboprophylaxis in primary prevention of cancer-associated venous thromboembolism in China.

Background and objective: Cancer-associated venous thromboembolism (CAVTE) is a preventable, life-threatening complication with a considerable morbidity and mortality. Primary venous thromboembolism (VTE) prophylaxis is currently recommended; however, the health and economic benefits have not been evaluated and compared in China. This study aimed to assess and compare the cost-effectiveness of anticoagulants in primary CAVTE prevention among cancer patients in China. Methods: A Markov model with a 5-year horizon was established to evaluate the costs and effectiveness of direct oral anticoagulants (DOACs) compared to low-molecular-weight heparins (LMWHs) and no prevention in primary prophylaxis of CAVTE in China. Key clinical outcomes were obtained from the available clinical trials, comparing DOACs (rivaroxaban and apixaban) with LMWHs or with no thromboprophylaxis. Utility and the cost inputs were all obtained from the published literature or local data with public sources. The total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were estimated as the main endpoints of the modal for each strategy. The assessment of uncertainty was performed involving deterministic sensitivity analysis and probabilistic sensitivity analysis (PSA). Impact of time horizon, generic drug price, and individual DOACs were assessed in scenario and subgroup analyses. Results: Primary prophylaxis using DOACs were projected to yield 1.866 QALYs at a cost of $3,287.893, resulting in the ICERs of $12,895.851 (DOACs vs. no-thromboprophylaxis) and $43,613.184/QALYs (LMWHs vs. DOACs). Sensitivity analysis revealed that ICER was sensitive to the VTE and bleeding risk, drug cost of anticoagulants, self-payment ratio, and overall death rate of cancer. Probabilistic sensitivity analysis showed that DOACs and LMWHs had a 48% and 45% probability of being cost-effective at a 5-year time horizon, respectively. When the time horizon extended to 10 years, DOACs achieved a cost-effective probability of 43%. Among individual DOACs, apixaban was found to be the preferred strategy in VTE prevention due to its incremental health gain with an acceptable cost increase. Conclusion: Primary thromboprophylaxis with DOACs was cost-effective in cancer patients at a willing-to-pay (WTP) threshold of $37,125.24/QALY in China. Cancer death rate, risk of VTE and major bleeding, and the drug cost assumed greater relevance and importance in the decision-making process for primary thromboprophylaxis in cancer.

The Effect of Intermittent Pneumatic Compression Device Combined with Low-Molecular-Weight Heparin on the Prevention of Deep Vein Thrombosis in Elderly Patients after Femoral Neck Fracture Surgery.

Aims/Background Femoral neck fractures in elderly patients carry a high risk of developing deep vein thrombosis (DVT) due to prolonged immobilization and surgical intervention. This study examines the effectiveness of combining intermittent pneumatic compression (IPC) with low-molecular-weight heparin (LMWH) for preventing DVT in elderly patients following femoral neck fracture surgery. Methods A total of 150 elderly patients with femoral neck fractures, admitted between January 2022 and January 2024, were retrospectively selected, and their clinical data were analyzed. Based on the treatment methods, the patients were divided into a control group (n = 71) and a study group (n = 79). The control group received LMWH treatment, while the study group received a combination of LMWH and IPC. The incidence of DVT, surgical outcomes, hip joint function, coagulation function indicators, hemodynamic indicators, and serum pro-inflammatory factors were compared between the two groups. Results The results showed that the incidence of DVT in the study group was lower than in the control group (p = 0.017). There were no significant differences between the two groups in terms of intraoperative blood loss, postoperative drainage volume, or Harris scores (p > 0.05). After the intervention, the study group demonstrated higher levels of average velocity (Va), peak blood flow velocity (Vp), and blood flow (BF) compared to the control group (p < 0.05). Additionally, the activated partial thromboplastin time (APTT) and prothrombin time (PT) were longer, while the D-dimer (D-D) level was lower in the study group (p < 0.05). The study group also exhibited lower levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8) (p < 0.05). Conclusion The results indicate that combining IPC with LMWH effectively reduces the incidence of postoperative DVT in elderly patients with femoral neck fractures, improves venous blood flow in the lower limbs, reduces vascular inflammation, and ensures safety.

Isothiocyanates attenuate heparin-induced proliferation of colon cancer cells in vitro.

Isothiocyanates (ITCs), prevalent in cruciferous vegetables, are known for their anticarcinogenic properties. Prior research has indicated that heparin can stimulate the growth of colon cancer cells. However, the implications of ITCs in the diet of cancer patients receiving heparin-based therapies have yet to be fully understood. This exploratory in vitro study examines the proliferative effects of low-molecular-weight heparin (LMWH) on human colon cancer cells and assesses the antiproliferative potential of four ITC compounds, exploring possible epidermal growth factor family of receptor tyrosine kinases (Erb-B) related mechanisms. We evaluated cell viability in HCT-116 and HT-29 cell lines following treatment with ITCs alone or combined with LMWH (20 µg/mL) at various concentrations (1-100 µM). Clonogenic and wound-healing assays were performed after 24 h of treatment with 5 µM ITCs. Additionally, messenger RNA (mRNA) and protein expression of Erb-B family genes was measured using quantitative polymerase chain reaction (qPCR) and Western blotting. Statistical analysis was conducted using analysis of variance (ANOVA) with Dunnett's post hoc test. Results indicated that the half-maximal inhibitory concentration (IC50) values for Phenylethyl isothiocyanate (PEITC), Benzyl isothiocyanate (BITC), and Sulforaphane (SFN) were lower than those of Allyl isothiocyanate (AITC) in LMWH-stimulated HCT-116 (20.77, 19.10, and 44.05 µM, respectively) and HT-29 (74.94, 26.77, and 43.49 µM, respectively). PEITC and SFN significantly reduced ErbB1 (epidermal growth factor receptor (EGFR)) and ErbB4 (receptor tyrosine-protein kinase erbB-4) expression, while BITC decreased ErbB2 (receptor tyrosine-protein kinase erbB-2) and transforming growth factor beta (TGF-ß) expression in HCT-116 cells (all, p < .05). PEITC, BITC, and SFN also increased proapoptotic Bax expression and decreased the antiapoptotic B-cell lymphoma 2 (Bcl-2) expression (all, p < .05). These findings suggest that specific ITCs may mitigate cancer cell proliferation induced by LMWH in cancer therapies, highlighting their potential therapeutic efficacy.

Thromboprophylaxis with intermediate dose enoxaparin during asparaginase containing induction for young adults with acute lymphoblastic leukemia.

Thrombosis rates among young adults receiving asparaginase (ASP) for acute lymphoblastic leukemia (ALL) can reach 34%, with highest risk during induction. Our institution implemented a standard practice of 1 mg/kg/day enoxaparin administered to young adults with ALL who are treated with ASP during induction. We performed a retrospective analysis of patients who received thromboprophylaxis with enoxaparin 1 mg/kg/day during ASP-containing induction for ALL at Oregon Health & Science University from 2012 to 2023. The primary outcome was the cumulative incidence of thrombosis during induction. Bleeding events were assessed. Sixty-two patients were included in our analysis. Four patients (6.5%; 95% CI 1.8%-15.7%) experienced a thrombotic event. Three events were catheter-associated and 1 event was a distal lower extremity deep vein thrombosis related to myositis. No cerebral sinus thromboses, thrombosis-related deaths or major bleeding events occurred. Intermediate-dose enoxaparin is a promising thromboprophylaxis strategy and warrants further prospective research.

Perinatal outcomes in indian women with Antiphospholipid Antibody Syndrome (APS): Five year experience from a tertiary care centre.

Background: Antiphospholipid Syndrome (APS) is a systemic autoimmune thrombophilic condition characterized by obstetric manifestations, including pregnancy loss, preeclampsia and fetal growth restriction. Early diagnosis and management are key to improve maternal and neonatal outcomes. Objective: The aim of this study is to assess the perinatal outcomes in APS, the development of various adverse pregnancy outcomes (APO), and their association with specific antibody profiles. Material methods: This observational study was carried out on booked cases of singleton pregnancy and diagnosed cases of primary APS in our High-Risk Pregnancy (HRP) clinic from January 2018 to December 2022 after approval from institutional ethics committee. Forty-three confirmed cases of primary APS were enrolled and started on low-dose aspirin and low-molecular-weight heparin (LMWH) as per the patient's body weight after confirmation of fetal heart activity radiologically until 36 weeks of gestation as a standard of care. Results: Forty patients (93 %) had obstetric APS, and three patients (7 %) had thrombotic APS. During the course of the current pregnancy, adverse pregnancy outcomes (APO) developed in 12 (30 %) out of 40 cases of obstetric APS and in all 3 patients with thrombotic APS. Preeclampsia was seen in 11 (25.5 %), FGR in 12 (27.9 %), and preterm birth in 7 (16.2 %) cases. Patients with an antibody profile showing the presence of Anti-ß2 GP-I positivity and ACL positivity had fewer APOs (20 % and 29 %) in comparison to patients with a LA and triple positive antibody profile (55 % and 50 %). Conclusion: Treatment of pregnant women with APS causes significant improvement in the live birth rate. The late pregnancy complications like preeclampsia, FGR, and premature birth, occurring despite treatment still remains a challenge and emphasizes the need for stringent antepartum surveillance and timely delivery.

Effectiveness and safety of low molecular weight heparin in the management of acute pancreatitis: a systematic review and meta-analysis.

BACKGROUND: Recent studies suggest that low-molecular-weight heparin (LMWH) may play a role in mitigating the severity of acute pancreatitis (AP). This systematic review and meta-analysis aims to synthesise existing evidence on the effectiveness and safety of LMWH in the treatment of moderately-severe and severe AP. METHODS: This systematic review and meta-analysis was conducted in accordance with the 2020 update of the PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. The systematic search was conducted in MEDLINE, the Cochrane Central Register of Controlled Trials, Scopus, and EMBASE, covering studies published up to February 2024. Randomised controlled trials (RCTs) and observational studies (n-RCTs) that reported the differences in the outcomes of AP for patients receiving LMWH in addition to the standard treatment (Intervention), compared to patients managed by standard treatment without LMWH (Control) were eligible. A random-effects model was used to calculate the pooled relative risk (RR) and mean differences (MD) with the corresponding 95% CI. RESULTS: Thirteen studies were included in the meta-analysis, all published between 2004 and 2022. Eight studies were RCTs, and five were n-RCTs. Data from 13,709 patients (6.971 Interventions and 6.738 Controls) were analysed. The comparison of Intervention and Control groups showed the superiority of LMWH to standard treatments in terms of overall mortality (RR = 0.44, 95% CI = 0.31; 0.64, P < 0.0001, I2 = 51%), acute necrotic collections (RR = 0.24, 95% CI = 0.09; 0.62, P = 0.003, I2 = 0%), and organ failure (RR = 0.67, 95% CI = 0.48; 0.93, P = 0.02, I2 = 78%). The Intervention group showed superior outcomes compared with the Control group for gastrointestinal bleeding (RR = 0.64, 95% CI = 0.44; 0.94, P = 0.02, I2 = 0%), length of hospital stay (MD= - 6.08, 95% CI = - 10.08; - 2.07, P = 0.003, I2 = 98%), need for operative interventions (RR = 0.50, 95% CI = 0.29; 0.87, P = 0.01, I2 = 61%), and vascular thrombosis (RR = 0.43, 95% CI = 0.31; 0.61, P < 0.00001, I2 = 0%). CONCLUSIONS: Moderate to high-quality evidence suggests that early intervention with LMWH could improve the prognosis of non-mild AP in terms of mortality, organ failure, and decreased incidence of vascular thrombosis. In light of our findings, integrating LMWH into the treatment regimen for moderate-severe to severe AP is advocated.

Immobilized high-performance heparin lyase III for efficient preparation of low molecular weight heparin.

Heparin lyase III has garnered widespread attention due to its high specificity and minimal loss of anticoagulant activity during the preparation of low molecular weight heparin (LMWH), a crucial anticoagulant drug in clinical practice. However, low expression levels and complex preparation processes limit its practical application. To address these challenges, high-performance Bacteroides thetaiotaomicron heparin lyase III (Bhep III) variants were engineered and immobilized for LMWH preparation. First, we enhanced enzyme expression by adding a solubility-enhancing tag and optimizing the N-terminal coding sequence, which resulted in a Bhep III activity level of 2.9 × 103 U/L with 8-fold increase. After evolution guided the design of rational mutations, the variant Bhep III K85A/Q95F/S471T generated higher activity (5.4 × 104 U/L in 5-L fermenter), which is, to our knowledge, the highest reported to date in the literature, being 1.7-fold that of the wild type and demonstrating 2-fold increase of the thermal stability. By screening and optimizing the C-terminal self-assembling tag, we successfully immobilized Bhep III, further increasing its thermal stability by 12-fold, and allowing for the multi-batch preparation of LMWH with simple centrifugation. The immobilized heparin lyase III demonstrated sufficient reusability in enzymatic reactions, facilitating efficient industrial-scale production of LMWH.

Efficiency of computerized clinical decision support systems involving anticoagulants: A flashmob study in Dutch hospital pharmacies.

AIMS: Computerized decision support systems (CDSSs) aim to prevent adverse drug events. However, these systems generate an overload of alerts that are not always clinically relevant. Anticoagulants are frequently involved in these alerts. The aim of this study was to investigate the efficiency of CDSS alerts on anticoagulants in Dutch hospital pharmacies. METHODS: A multicentre, single-day, cross-sectional study was conducted using a flashmob design in Dutch hospital pharmacies, which have CDSSs that operate on both a national medication surveillance database and on self-developed clinical rules. Hospital pharmacists and pharmacy technicians collected data on the number and type of alerts and time needed for assessing these alerts. The primary outcome was the CDSS efficiency on anticoagulants, defined as the percentage of alerts on anticoagulants that led to an intervention. Secondary outcomes where among other CDSSs efficiency related to any medications and the time expenditure. Descriptive data-analysis was used. RESULTS: Of the 69 hospital pharmacies invited, 42 (61%) participated. The efficiency of CDSS alerts on anticoagulants was 4.0% (interquartile range [IQR] 14.0%) for the national medication surveillance database alerts and 14.3% (IQR 40.0%) for alerts from clinical rules. For any medication, the efficiency was lower: 1.8% (IQR 7.5%) and 13.4% (IQR 21.5%) respectively. The median time for assessing the relevance of all alerts was 2 (IQR 1:21) h/day for pharmacists and 6 (IQR 5:01) h/day for pharmacy technicians. CONCLUSION: CDSS efficiency is generally low, both for anticoagulants and any medication, while the time investment is high. Optimization of CDSSs is needed.

Values and preferences towards the use of prophylactic low-molecular-weight heparin during pregnancy: a convergent mixed-methods secondary analysis of data from the decision analysis in shared decision making for thromboprophylaxis during pregnancy (DASH-TOP) study.

BACKGROUND: Venous thromboembolism (VTE) in pregnancy is a major cause of maternal morbidity and mortality, and the use of preventive low-molecular-weight heparin (LMWH) can be challenging. Clinical guidelines recommend eliciting pregnant individuals' preferences towards the use of daily injections of LMWH and discussing the best option through a shared decision-making (SDM) approach. Our aim was to identify individuals' preferences concerning each of the main clinical outcomes, and categorize attributes influencing the use of LMWH during pregnancy. METHODS: Design: Convergent mixed-methods. PARTICIPANTS: Pregnant women or those planning a pregnancy with VTE recurrence risk. INTERVENTION: A SDM intervention about thromboprophylaxis with LMWH in pregnancy. ANALYSIS: Quantitatively, we report preference scores assigned to each of the health states. Qualitatively, we categorized preference attributes using Burke's pentad of motives framework: act (what needs to be done), scene (patient's context), agent (perspectives and influence of people involved in the decision), agency (aspects of the medication), and purpose (patient's goals). We use mixed-method convergent analysis to report findings using side-by-side comparison of concordance/discordance. RESULTS: We comprehensively determined preferences for using LMWH by pregnant individuals at risk of VTE: through value elicitation exercises we found that the least valued health state was to experience a pulmonary embolism (PE), followed by major obstetrical bleeding (MOB), deep vein thrombosis (DVT), and using daily injections of LMWH (valued as closest to a 'healthy pregnancy'); through interviews we found that: previous experiences, access to care (scene) and shared decision-making (agent) affected preferences. LMWH's benefits were noted, but substantial drawbacks were described (agency). For participants, the main goal of using LMWH was avoiding any risks in pregnancy (purpose). Side-by-side comparisons revealed concordance and discordance between health states and motives. CONCLUSIONS: Mixed-methods provide a nuanced understanding of LMWH preferences, by quantifying health states preferences and exploring attributes qualitatively. Incorporating both methods may improve patient-centered care around preference-sensitive decisions in thromboprophylaxis during pregnancy.

Bridging With Low-Molecular-Weight Heparin Versus Antiplatelet Therapy in Patients Undergoing Noncardiac Surgery After Percutaneous Coronary Intervention: A Comprehensive Review.

BACKGROUND: This review article discussed the use of bridging therapy with low-molecular-weight heparin (LMWH) in patients who undergo noncardiac surgery (NCS) after percutaneous coronary intervention (PCI). HYPOTHESES: Patients who undergo PCI are at an increased risk of thrombotic events due to their underlying cardiovascular disease. However, many of these patients may require NCS at some point in their lives, which poses a significant challenge for clinicians as they balance the risk of thrombotic events against the risk of bleeding associated with antithrombotic therapy. RESULTS: This review evaluates the current evidence on the use of bridging therapy with LMWH in patients undergoing NCS after PCI, focusing on outcomes related to the efficacy and safety of antithrombotic therapy. The article also discusses the limitations of the current evidence and highlights areas where further research is needed to optimize the management of antithrombotic therapy in this patient population. CONCLUSION: The goal of this review was to provide clinicians with a comprehensive summary of the available evidence to guide clinical decision-making and improve patient outcomes.

Preventing Postpartum Venous Thromboembolism With Low-Molecular-Weight Heparin: The PP-HEP Pilot Randomised Controlled Trial.

OBJECTIVE: Uncertainty surrounds the risk-benefit of low-molecular-weight heparin to prevent postpartum venous thromboembolism (VTE). Data from randomised clinical trials (RCT) are critically needed, but recent feasibility studies in North America yielded low participation rates, with <1 enrolment per month per centre. Our aim was to assess the feasibility of a trial of postpartum short-term enoxaparin in Europe. DESIGN: Pragmatic, open-label pilot randomised controlled trial (RCT). SETTING: Swiss tertiary hospital. POPULATION: Postpartum women, within 48 h of delivery, deemed at intermediate risk of VTE with at least one major risk factor (morbid obesity, thrombophilia, emergency caesarean section, pre-eclampsia, preterm delivery, intrauterine growth restriction or systemic peripartum infection) and/or at least two minor risk factors. METHODS: Participants were randomised to enoxaparin 40-60 mg once daily for 10 days or no treatment, with a 90-day follow-up. MAIN OUTCOME MEASURES: Participation rate and study acceptance (randomised participants among women in whom informed consent was sought). RESULTS: Recruitment was open for 25 weeks in 2022. Among 1504 postpartum women, 480 were eligible and 77 were randomised. The recruitment rate was 3.1 per week (13.3 per month) and the study acceptance was 23.8%. At 3 months, there was no VTE event, but one major, one nonmajor obstetrical bleeding and one surgical site complication, all in the enoxaparin group. CONCLUSIONS: This pilot RCT of postpartum thromboprophylaxis set in Switzerland yielded greater participation rate and acceptance than previous attempts in North America. It calls for a large, international, collaborative trial to guide this important clinical decision. TRIAL REGISTRATION: ClinicalTrial.gov identifier: NCT05878899 and NCT04153760.

Heparin therapy in sepsis and sepsis-associated disseminated intravascular coagulation: a systematic review and meta-analysis.

BACKGROUND: Sepsis is a life-threatening condition that affects 49 million people annually. Managing sepsis-associated coagulopathy poses a significant challenge due to its high mortality rates in intensive care. Recent reports suggest that administering heparin may offer potential survival benefits in sepsis and coronavirus disease cases. However, there is currently no established evidence supporting the use of heparin for sepsis. Thus, in this study, we aimed to assess the efficacy of heparin administration in patients with sepsis. METHODS: A systematic review was conducted following the PRISMA guidelines. The searches included MEDLINE, Cochrane, and Japanese databases up to January 2023. The inclusion criteria consisted of randomized control trials (RCTs) involving adult sepsis patients receiving heparin. The risk of bias was assessed using RoB2, and the data extraction included 28-day mortality and bleeding complications. RESULTS: Out of 1733 initial articles, only three studies met the inclusion criteria. The analysis, which included 426 patients, showed no significant difference in 28-day and in-hospital mortality between the heparin and control groups (risk ratio [RR] = 0.86, 95% confidence interval [CI]: 0.60-1.24). Subgroup analysis of sepsis-associated disseminated intravascular coagulation (DIC) patients (n = 109) also did not show a significant reduction in mortality (RR = 0.84, 95% CI: 0.51-1.38). Heterogeneity was zero, and no publication bias was observed. Additionally, there was significant difference in bleeding complications (RR = 0.49, 95% CI: 0.24-0.99, p = 0.047). CONCLUSIONS: This meta-analysis did not demonstrate a survival benefit of heparin administration in patients with sepsis and sepsis-associated DIC. Further investigation into the potential benefits of heparin is warranted. Moreover, the analysis revealed no increase in bleeding risks with heparin administration; instead, a significant reduction in the risk of bleeding was noted. TRIAL REGISTRATION: This review was preregistered with PROSPERO (registration: CRD42023385091).

Effectiveness and safety of rivaroxaban or low-molecular-weight heparin in non-major orthopedic surgery: a meta-analysis of randomized controlled trials.

BACKGROUND: Patients undergoing non-major orthopedic surgery often face an increased risk of venous thromboembolism due to the necessity of immobilization postoperatively. Current guidelines commonly recommend the use of low-molecular-weight heparin (LMWH) for prophylaxis, but it is associated with low patient compliance and certain side effects. We conducted a meta-analysis of randomized controlled trials (RCTs) to assess the effectiveness and safety of rivaroxaban or LMWH for thromboprophylaxis following non-major orthopedic surgery. METHOD: Relevant literature was systematically searched in PubMed, Web of Science, Cochrane Library, and Embase from their inception to October 1, 2023, to evaluate the effectiveness and safety of rivaroxaban or LMWH in RCTs for thromboprophylaxis following non-major orthopedic surgery. RESULTS: A total of 5 randomized controlled trials involving 5,101 patients were included. There was no statistically significant difference in the preventive effect against venous thromboembolism (VTE) when using rivaroxaban or LMWH following non-major orthopedic surgery (RR 0.80; 95%CI 0.31 to 2.07). In terms of safety, there was also no statistically significant difference in the incidence of bleeding events in patients undergoing non-major orthopedic surgery when using rivaroxaban or LMWH (RR 1.15; 95% CI 0.75 to 1.76). CONCLUSION: In non-major orthopedic surgery, the risk of venous thromboembolism and bleeding complications is similar when using rivaroxaban or LMWH.

Umbilical Vascular Thromboembolism: High-Risk Factors, Diagnosis, Management, and Pregnancy Outcomes: A Scoping Review.

Umbilical vascular thromboembolism is a rare condition that can lead to serious consequences such as fetal hypoxia, fetal growth restriction, and even stillbirth. However, there is currently a lack of research on the pathology, pathogenesis, clinical management, and prognosis of this condition. Therefore, the purpose of this article is to analyze this condition's high-risk factors, clinical characteristics, pregnancy management, and discuss its corresponding pregnancy outcomes. Databases such as PubMed are searched using the relevant keywords of umbilical vascular thromboembolism in worldwide. And related information is analyzed such as maternal risk factors, fetal risk factors, umbilical cord and placental risk factors, and pregnancy outcomes. The literature search yields 113 articles, 64 of which meet the inclusion criteria for umbilical vascular thromboembolism. There are 4 retrospective cohort studies and 8 case series, the rest are all case reports. A total of 262 cases of umbilical vascular thromboembolism are found. The most common maternal complications and fetal related risk factors are diabetes (25 cases, 9.5%) and stillbirths (106 cases, 40.5%), respectively. Among these 262 cases, 98 (37.4%) cases are found by prenatal ultrasound to have umbilical vascular thromboembolism and the fetus is in a viable state with complete clinical information. In addition, considering the effectiveness and safety of low molecular weight heparin in thromboembolic conditions, twenty-four patients of umbilical artery thromboembolism attempted to use low molecular weight heparin during observation. Maternal diabetes was the highest risk factor for this condition. When umbilical artery thromboembolism occurs, the incidence of stillbirth increases. Premature patients with this condition can continue their pregnancy under close external monitoring. However, due to the small sample size, further research is needed.

Injection Techniques to Reduce Adverse Effects of Subcutaneous Low-Molecular-Weight Heparin Among Patients With Cardiovascular Diseases: A Scoping Review.

AIM(S): To systematically review the existing literature and address the following research question: What are the most effective techniques used to minimise adverse effects resulting from subcutaneous injections of low-molecular-weight heparin among patients with cardiovascular diseases? DESIGN: A scoping review. METHODS: A comprehensive search was conducted across multiple databases, including CINAHL, PubMed, EMBASE and the Cochrane Library, from 1 February 2014 to 31 January 2024. Participants were aged 18 years or older, diagnosed with venous thromboembolism or arterial thromboembolism and had prescribed subcutaneous injections of low-molecular-weight heparin. The collected data were analysed following the Joanna Briggs Institute approach, and it was organised and categorised based on the main objectives of the review. RESULTS: Twenty studies were eligible, including 1 best practice project, 7 randomised controlled trials and 9 quasi-experimental studies. The techniques under investigation encompassed various aspects, including the injection site, injection duration (e.g., 30 s vs. 10 s), injection method (e.g., needle insertion angle), duration of needle withdrawal after injection, pressure application time and cold pressure. Preliminary evidence suggests that techniques such as using the abdominal site and slower injection rates may help reduce adverse effects. However, the optimal parameters for injection duration, waiting time, pressure and cold application, including the duration of these applications, remain uncertain due to limitations in sample size and heterogeneity in interventions and outcome measures across the studies. CONCLUSIONS: Ensuring the accurate administration of low-molecular-weight heparin is of utmost importance as it plays a critical role in decreasing mortality rates and minimising substantial healthcare costs linked to complications arising from incorrect administration. The findings from the current review have significantly contributed to strengthening the evidence base in this field, providing more robust and reliable information. IMPLICATIONS FOR THE PROFESSION: This review emphasises the significance of implementing standardised subcutaneous injection techniques for low-molecular-weight heparin in patients with cardiovascular disease in order to reduce complications and enhance patient outcomes. REPORTING METHOD: This study followed the applicable guidelines established by the PRISMA 2020 statement. The PRISMA checklist for systematic reviews was utilised for reporting purposes. PATIENT OR PUBLIC CONTRIBUTION: There is no patient or public contribution to declare. TRIAL REGISTRATION: OSF registries: osf.io/phk72.

Comparison of direct oral anticoagulant (DOAC) versus low-molecular-weight heparin (LMWH) for venous thromboprophylaxis after radical cystectomy: A systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: Radical cystectomy in bladder cancer patients can result in postoperative complications, including venous thromboembolism (VTE), with an incidence reported between 3% and 11.6%. Although low-molecular-weight heparin (LMWH) is the recommended prophylactic treatment, challenges such as financial constraints and patient adherence remain. Direct Oral Anticoagulants (DOACs) present an alternative, but their comparative efficacy and safety against LMWHs in preventing VTE after radical cystectomy need further evaluation. This study aims to compare the efficacy and safety of LMWHs vs. DOACs for VTE prophylaxis following radical cystectomy. MATERIALS AND METHODS: A systematic search was performed across 3 electronic databases to identify relevant studies utilizing DOACs and LMWHs for VTE prophylaxis after radical cystectomy. The primary outcomes of interest were VTE and bleeding events. Fixed-effect models were employed to summarize the outcomes, with results presented as odds ratios (OR) and their corresponding 95% confidence intervals (CI). RESULTS: The analysis included a total of 541 patients from three studies. The pooled data indicated that patients on DOACs had a statistically nonsignificant lower odds of VTE (OR 0.41 [95% CI 0.13-1.36], P = 0.15) and a statistically nonsignificant higher odds of bleeding events (OR 3.03 [95% CI 0.53-17.23], P = 0.21). CONCLUSIONS: Our findings suggest that DOACs are comparable to LMWHs in terms of VTE and bleeding events for thromboprophylaxis following radical cystectomy. The choice of prophylactic agent can be guided by patient preference and clinical judgment. However, additional randomized controlled trials with larger sample sizes are necessary to confirm these findings.