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Objective This paper was aimed at unveiling the effect of low-molecular-weight heparin calcium (LMWH) combined with magnesium sulfate and labetalol on coagulation, vascular endothelial function, and pregnancy outcome in early-onset severe preeclampsia (EOSP). Methods Pregnant women with EOSP were divided into the control group and the study group, each with 62 cases. Patients in the control group were treated with labetalol and magnesium sulfate, and those in the study group were treated with LMWH in combination with the control grou Blood pressure (systolic blood pressure [SBP] and diastolic blood pressure [DBP]), 24-h urine protein, coagulation indices [D-dimer (D-D), plasma fibrinogen (Fg), prothrombin time (PT), activated partial thromboplastin time (APTT), and prothrombin time (TT)], endothelial function [endothelin (ET-1) and nitric oxide (NO)], oxidative stress indices [oxidized low-density lipoproteins (ox-LDL), lipid peroxidation (LPO), superoxide dismutase (SOD), and malondialdehyde (MDA)], pregnancy outcome, and adverse effects occurred in the two groups were compared. Results After treatment, lower SBP, DBP, and 24-h urine protein levels; lower Fg and D-D levels; higher PT, APPT, and TT levels; higher NO levels; lower ET-1 levels; lower ox-LDL, MDA, and LPO levels; higher SOD levels; and lower incidence of adverse pregnancy and adverse reactions were noted in the study group in contrast to the control group. Conclusion EOSP patients given with LMWH combined with magnesium sulfate and labetalol can effectively reduce the patient’s blood pressure and urinary protein level; improve coagulation function, oxidative stress, and vascular endothelial function indices; reduce the adverse pregnancy outcomes; and improve the safety of treatment.

Low-molecular-weight heparin (LMWH) is widely used to treat recurrent pregnancy loss (RPL) because of its anti-coagulant effects. Although in vitro studies have suggested additional immunological effects, these are debated. We therefore investigated whether LMWH could modulate immune responses in vivo during pregnancy of women with unexplained RPL. A Swedish open multi-centre randomised controlled trial included 45 women treated with tinzaparin and 42 untreated women. Longitudinally collected plasma samples were obtained at gestational weeks (gw) 6, 18, 28 and 34 and analysed by multiplex bead technology for levels of 11 cytokines and chemokines, chosen to represent inflammation and T-helper subset-associated immunity. Mixed linear models test on LMWH-treated and untreated women showed differences during pregnancy of the Th1-associated chemokines CXCL10 (p = 0.01), CXCL11 (p < 0.001) and the Th17-associated chemokine CCL20 (p = 0.04), while CCL2, CCL17, CCL22, CXCL1, CXCL8, CXCL12, CXCL13 and IL-6 did not differ. Subsequent Student’s t-test showed significantly higher plasma levels of CXCL10 and CXCL11 in treated than untreated women at gw 28 and 34. The consistent increase in the two Th1-associated chemokines suggests a potential proinflammatory and unfavourable effect of LMWH treatment during later stages of pregnancy, when Th1 immunity is known to disrupt immunological tolerance.

Venous thromboembolism (VTE) is considered a potentially serious complication of knee arthroscopy and leads to conditions such as deep venous thrombosis (DVT) and pulmonary embolism (PE). Low-molecular-weight heparin (LMWH) is widely employed in knee arthroscopy to reduce perioperative thromboembolic complications. However, the efficacy and safety of LMWH in knee arthroscopy remains unclear. Seven randomized controlled clinical trials on LMWH in knee arthroscopy were identified and included in this meta-analysis. The main outcomes of the effectiveness (prevention of DVT and PE) and complications (death, major bleeding, and minor bleeding) of LMWH in knee arthroscopic surgery were assessed using Review Manager 5.3 software. The meta-analysis indicated that LMWH prophylaxis comprised 79% of asymptomatic DVT. No association was found in symptomatic VTE (RR: 0.90; 95% confidence interval [CI]: 0.39-2.08; P = 0.80), symptomatic DVT (RR: 0.79; 95% CI: 0.28-2.23; P = 0.66), symptomatic PE (RR: 1.36; 95% CI: 0.37-4.97; P = 0.64) and major bleeding (RR: 0.70; 95% CI: 0.12-3.95; P = 0.68) risk during LMWH prophylaxis were identified. Death was not reported in these studies. Moreover, there was a lower incidence of minor bleeding (RR: 0.64; 95% CI: 0.49 to 0.83; P = 0.001) in the control group than in the LMWH group. Compared with the control group, the group treated with LMWH after knee arthroscopy was no association in reducing the symptomatic VTE rate, symptomatic DVT rate or symptomatic PE rate. The symptomatic VTE rate was 0.5% (11/2,166) in the LMWH group versus 0.6% (10/1,713) in the control group. Although the limitations of this meta-analysis cannot be ignored, the results of our study show that LMWH after knee arthroscopy is ineffective. We recommend that LMWH should not be routinely provided for knee arthroscopy. ClinicalTrials.gov NCT03164746.

Ultralow molecular weight (ULAAW) heparins are sulfated glycans that are clinically used to treat thrombotic disorders. ULMW heparins range from 1500 to 3000 daltons, corresponding from 5 to 10 saccharide units. The commercial drug Arixtra (fondaparinux sodium) is a structurally homogeneous ULMW heparin pentasaccharide that is synthesized through a lengthy chemical process. Here, we report 10- and 12-step chemoenzymatic syntheses of two structurally homogeneous ULMW heparins (MW = 1778.5 and 1816.5) in 45 and 37% overall yield, respectively, starting from a simple disaccharide. These ULMW heparins display excellent in vitro anticoagulant activity and comparable pharmacokinetic properties to Arixtra, as demonstrated in a rabbit model. The chemoenzymatic approach is scalable and shows promise for a more efficient route to synthesize this important class of medicinal agent.

Anticoagulant agents are widely used in the treatment of thromboembolic events and in stroke prevention. Data about their effects on bone tissue are in some cases limited or inconsistent (oral anti-vitamin K agents), and in others are sufficiently strong (heparins) to suggest caution in their use in subjects at risk of osteoporosis. This review analyses the effects of this group of drugs on bone metabolism, on bone mineral density, and on fragility fractures. A literature search strategy was developed by an experienced team of specialists by consulting the MEDLINE platform, including published papers and reviews updated to March 2019. Literature supports a detrimental effect of heparin on bone, with an increase in fracture rate. Low molecular weight heparins (LMWHs) seem to be safer than heparin. Although anti-vitamin K agents (VKAs) have a significant impact on bone metabolism, and in particular, on osteocalcin, data on bone mineral density (BMD) and fractures are contrasting. To date, the new direct oral anticoagulants (DOACs) are found to safe for bone health.

Low molecular weight heparin (LMWH) is a glycosaminoglycan long known for its anticoagulant properties. In recent times, recent evidence has associated this drug with extra pleiotropic anticoagulant effects that have also proven useful in the management of the treatment of COVID-19 infection indicating that heparin may play other roles in the management of the disease in addition to the prevention of thrombosis. Clinical observations and in vitro studies support that heparin has a potential multi-target effect. To date, the molecular mechanisms of these pleiotropic effects are not fully understood. This brief review presents some of the evidence from clinical and animal studies and describes the potential molecular mechanisms by which heparin may exert its anti-inflammatory/immunoregulatory and antiviral effects.

Heparin analogs can serve as potent anticoagulants, but heterogeneous structures in some preparations and lack of antidote for others can complicate treatments. A chemoenzymatic method that prevents reversible epimerization now enables reversible application of defined constructs in cells and mice. Low-molecular-weight heparins (LMWHs) are carbohydrate-based anticoagulants clinically used to treat thrombotic disorders, but impurities, structural heterogeneity or functional irreversibility can limit treatment options. We report a series of synthetic LMWHs prepared by cost-effective chemoenzymatic methods. The high activity of one defined synthetic LMWH against human factor Xa (FXa) was reversible in vitro and in vivo using protamine, demonstrating that synthetically accessible constructs can have a critical role in the next generation of LMWHs.

Clopidogrel is usually discontinued 5–7 days before elective surgery to reduce the risk of bleeding. However, the perioperative safety of patients receiving low-molecular-weight heparin (LMWH) bridging therapy or continuing clopidogrel therapy remains unknown. We identified patients who received clopidogrel for cardiovascular diseases and underwent elective surgery at a large central hospital in China between June 2022 and January 2024. The primary endpoints were perioperative blood transfusion events and bleeding-related reoperations. A total of 62 patients who received clopidogrel and underwent abdominal surgery were included in this study. Based on the preoperative clopidogrel therapy strategy, patients were categorised into three groups: the LMWH bridging group (clopidogrel withdrawal followed by LMWH bridging therapy for 5-7 days; n = 22), the no-bridging group (clopidogrel withdrawal for 5-7 days; n = 26), and the continued group (clopidogrel therapy maintained; n = 24). Perioperative blood transfusion rates were higher in the LMWH bridging and continued groups. However, there was not a significant distinction (P = .197). Additionally, hospital stay length, bleeding-related reoperation, and 3-month mortality were similar across the groups (P > .05). No patients experienced myocardial infarction or stroke within 3 months post-procedure. Patients who received preoperative LMWH bridging therapy or continued clopidogrel therapy had a slightly higher risk of perioperative bleeding. These findings need to be confirmed by further randomised controlled trials.

PurposeTo test whether a multicomponent intervention would increase the use of low molecular weight heparin (LMWH) over unfractionated heparin (UFH) for venous thromboembolism (VTE) prophylaxis in critically ill patients and change patient outcomes and healthcare utilization.MethodsControlled pre–post trial of 12,342 adults admitted to 11 ICUs (five intervention, six control) May 1, 2015 to April 30, 2017 with no contraindication to pharmacological prophylaxis and an ICU stay longer than 24 h. Models were developed to examine temporal changes in ICU VTE prophylaxis (primary outcome), VTE, major bleeding, heparin-induced thrombocytopenia (HIT), death and hospital costs.ResultsThe use of LMWH increased from 45.9% to 78.3% of patient days in the intervention group and from 37.9% to 53.3% in the control group, an absolute increase difference of 17.0% (32.4% vs. 15.4%, p = 0.001). Changes in the administration of UFH were inversely related to those of LMWH. There were no significant differences in the adjusted odds of VTE (ratio of odds ratios [rOR] 1.13, 95% CI 0.51–2.46) or major bleeding (rOR 1.22, 95% CI 0.97–1.54) post-implementation of the intervention (compared to pre-implementation) between the intervention group and the control group. HIT was uncommon in both groups (n = 20 patients). There were no significant changes for ICU and hospital mortality, length of stay and costs. Results were similar when stratified according to reason for ICU admission, patient weight and kidney function.ConclusionsA multicomponent intervention changed practice, but not clinical and economic outcomes. The benefit of implementing LMWH for VTE prophylaxis under real-world conditions is uncertain.