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In a randomized trial, 1050 patients with cancer who had acute venous thromboembolism were assigned to receive either dalteparin or edoxaban for 6 to 12 months. Edoxaban was noninferior to dalteparin with respect to the outcome of recurrent venous thromboembolism or major bleeding.

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.

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.

Low-molecular-weight heparin (LMWH) is usually recommended for the treatment of cancer-associated thrombosis (CAT) but this treatment requires burdensome daily injections. We did a systematic review to compare the efficacy and safety of direct oral anticoagulants (DOAC), vitamin K antagonists (VKA) and LMWH in patients with CAT. We searched Pubmed, Embase and CENTRAL for randomised controlled trials comparing DOAC, VKA and LMWH in patients with CAT. Pairwise and network meta-analyses were computed for venous thromboembolism (VTE) recurrence and bleeding complications. We identified 14 studies, including 4,661 patients. In pairwise comparison, DOAC were superior to LMWH to prevent VTE recurrence (HR 0.63; 95% CI 0.42-0.96) and LMWH was superior to VKA (HR 0.53; 95% CI 0.40-0.70). The rate of major bleeding was higher with DOAC compared to LMWH (HR 1.78; 95% CI 1.11-2.87). In the network meta-analysis, DOAC had a lower, but non-significant, rate of VTE recurrence compared to LMWH (HR 0.74; 95% CI 0.54-1.01). Both DOAC (HR 0.42; 95% CI 0.29-0.61) and LMWH (HR 0.57; 95% CI 0.44-0.75) were associated with lower rates of recurrence compared to VKA. No significant difference in major bleeding rate was observed in the network meta-analysis. Inconsistency was observed between pairwise and network meta-analysis comparisons for major bleeding. DOAC are effective to prevent VTE recurrence in patients with CAT but are associated with an increased risk of bleeding compared to LMWH. The choice of anticoagulant should be personalised, taking into account the patient's bleeding risk, including cancer site, and patient's values and preferences.

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.

Venous thromboembolism (VTE) includes deep vein thrombosis (DVT) and pulmonary embolism (PE). Certain abdominopelvic cancer surgeries are associated with a six to 14-fold increased risk of DVT versus surgeries for benign disease, and extended thromboprophylaxis using perioperative LMWHs may further reduce VTE rates over standard duration administration. This review assesses the value of extended low molecular weight heparin (LMWH) thromboprophylaxis as a recommended strategy after abdominopelvic cancer surgery. Six eligible randomized controlled trials (RCTs), seven meta-analyses (MAs), and five non-randomized cohort studies were identified evaluating extended versus standard thromboprophylaxis following abdominopelvic cancer surgery. Available evidence showed significantly reduced rates of VTE for extended versus standard LMWH thromboprophylaxis following abdominopelvic cancer surgery, with some studies showing trends toward reduced rates of symptomatic VTE events. Many of these studies showed significantly reduced rates of proximal DVT and some showed trends toward reduced PE, suggesting potentially important clinical benefits. •Abdominopelvic cancer surgery has high risk of venous thromboembolism events.•Evidence shows benefit for extended versus standard duration thromboprophylaxis.•No increased bleeding or treatment-related deaths were observed.•Individual risk factors should guide thromboprophylactic duration.

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.

Cancer-associated thrombosis, with the incidence rising over the years, is associated with significant morbidity and mortality in patients with cancer. Recent advances in the treatment of cancer-associated venous thromboembolism (VTE) include the introduction of direct oral anticoagulants (DOACs), which provide a more convenient and effective option than low-molecular-weight heparin (LMWH). Nonetheless, important unmet needs remain including an increased risk of bleeding in certain patient subgroups such as those with gastroesophageal cancer, concerns about drug-drug interactions, and management of patients with severe renal impairment. Although DOACs are more convenient than LMWH, persistence can decline over time. Factor XI inhibitors have potential safety advantages over DOACs because factor XI appears to be essential for thrombosis but not hemostasis. In phase II trials, some factor XI inhibitors were superior to enoxaparin for the prevention of VTE after knee replacement surgery without increasing the risk of bleeding. Ongoing trials are assessing the efficacy and safety of factor XI inhibitors for the treatment of cancer-associated VTE. This narrative review summarizes advances in the treatment of cancer-associated venous thromboembolism, outlines key unmet needs with the current treatment, and discusses how factor XI inhibitors may address the current knowledge gaps.

Objective This study aimed to observe and compare the efficacy and safety of different anticoagulants combined with immunotherapy and chemotherapy for advanced nonsmall cell lung cancer (NSCLC). Methods In this prospective, randomized, controlled clinical trial, treatment-naïve subjects with stage I I I B– I V NSCLC were enrolled and randomly assigned to the control group (tislelizumab + chemotherapy), low-molecular-weight heparin (LMWH) group (LMWH + tislelizumab + chemotherapy), and rivaroxaban group (rivaroxaban + tislelizumab + chemotherapy). The primary endpoint was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and safety. Results In this study, 143 patients were enrolled, including 46 in the control group, 48 in the LMWH group, and 49 in the rivaroxaban group. The median PFS of the control, LMWH, and rivaroxaban groups was 8.5 months (95%CI: 7.6–9.4), 8.6 months (95% CI: 8.1–9.1), and 11.2 months (95% CI: 9.4–13.0), respectively. Kaplan–Meier curve analysis showed no significant difference in PFS between the LMWH and control groups (HR = 1.041, 95% CI: 0.676–1.604; P  = 0.852). The rivaroxaban group had significantly higher PFS than the control (HR = 0.766, 95% CI: 0.623–0.967; P  = 0.021) and LMWH groups (HR = 0.582, 95% CI: 0.376–0.901; P  = 0.013). No significant differences were observed in the ORR, complete response, partial response, DCR, or stable disease among the three groups (all P  > 0.05). Conclusions Rivaroxaban combined with immune checkpoint inhibitors and chemotherapy has potential advantages in NSCLC treatment. It may enhance the antitumor efficacy by regulating immune functions, thereby prolonging the PFS of patients. Trial registration Trial Registration: ChiCTR2500106653.

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.