Anticoagulant therapy has undergone substantial evolution over the past century, progressing from early parenteral agents such as heparin to vitamin K antagonists (VKAs) and, more recently, to direct oral anticoagulants (DOACs). This review provides an overview of the major classes of anticoagulants, including unfractionated heparin (UFH), low molecular weight heparin (LMWH), fondaparinux, direct thrombin inhibitors, VKAs, and DOACs, with emphasis on their mechanisms of action, clinical applications, laboratory monitoring, and reversal strategies. While UFH remains widely used in acute settings, its unpredictable pharmacokinetics and risk of heparin induced thrombocytopenia have led to increased use of LMWH and fondaparinux. VKAs, historically the cornerstone of oral anticoagulation, are limited by variable dosing requirements and the need for routine monitoring. In contrast, DOACs have transformed anticoagulation management through predictable pharmacokinetics, fixed dosing, and improved safety profiles, and are now first line therapies for several thromboembolic conditions. The development of targeted reversal agents, including protamine, vitamin K, prothrombin complex concentrates, idarucizumab, and andexanet alfa, has significantly enhanced the safety of anticoagulant therapy in the setting of major bleeding or urgent procedures. Laboratory assessment remains critical for selecting anticoagulants and evaluating clinical scenarios, with evolving roles for anti-Xa assays, thrombin-based assays, and mass spectrometry techniques. Emerging anticoagulants targeting factors XI, XII, and XIII represent a promising future direction with the potential to further reduce bleeding risk while maintaining efficacy. Overall, continued advances in anticoagulant pharmacology, monitoring, and reversal strategies are driving a shift toward safer and more individualized patient care.

Sulfated polysaccharides (SPS) are a class of biomacromolecules bearing a large negative charge; due to their structural complexity and diverse biological activities, they had become a hot topic in glycoscience research. This paper focused on recent advances in the study of SPS, systematically discussing both natural and synthetic sources. It explored the structural composition of four typical SPS namely heparin, chondroitin sulfate, fucoidan, and fondaparinux sodium, as well as their biological activities, including antiviral, antioxidant, antitumor, anticoagulant, and immunomodulatory effects. Subsequently, the paper analyzed the degradation mechanisms of these polysaccharides by various types of microorganisms, particularly gut microbiota, with a particular emphasis on the degradation of SPS by the Bacteroidetes phylum (Sus-like system), Lactic acid bacteria (LAB), and Micrococcus, then compared their degradation strategies. The roles of various active enzymes in the degradation process were analyzed, and the role of SPS synthesized by microorganisms themselves in their survival and development was discussed. The unique structure of SPS and their corresponding biological activities gave them enormous application potential in fields such as synthetic biology, metabolic engineering, and healthcare.

The chemokine CCL20/MIP3α plays an important role in the migration of dendritic cells and several lymphocytes. This 70-residue protein is also implicated in various diseases, such as rheumatoid arthritis, psoriasis, sepsis and numerous forms of cancer. In addition, as the most basic human chemokine, CCL20 also displays direct antimicrobial and antibiofilm activities. The binding and oligomerization of chemokines to cell surface glycosaminoglycans (GAG) can play an important role during receptor activation; therefore we have studied the interactions of CCL20 with fondaparinux. This anticoagulant drug is a uniform sulfated linear pentasaccharide that structurally closely resembles the heterogenous low molecular weight heparins that have often been used to study GAG-protein binding in solution. Using multidimensional multinuclear NMR spectroscopy, we could map out the distinct GAG/fondaparinux binding sites on the monomeric (pH 5.5) and dimeric (pH 7.5) forms of the CCL20 protein surface. In the second part of this study, we showed that CCL20-(51-70), the recombinant 20-residue carboxyterminal helical peptide of CCL20, interacted weakly with fondaparinux. We also surveyed several host-defence properties of this peptide. In comparison to several other well-characterized peptides, CCL20-(51-70) displayed potent antibiofilm and antimicrobial activities against a pathogenic Gram-positive Staphylococcus aureus MRSA strain. It also displayed somewhat lower activities against the Gram-negative Pseudomonas aeruginosa PAO1 strain. These results highlight the potential of CCL20-(51-70) as a potent host-defence peptide, that could play a role in eradicating bacterial biofilms, particularly for Gram-positive pathogenic bacteria.

Heparan sulfate proteoglycans (HSPGs) facilitate interactions between growth factors and their receptors, regulating signaling pathways involved in angiogenesis and cell proliferation. However, the structural heterogeneity and synthetic inaccessibility of native heparan sulfate (HS) have limited systematic exploration of structure-activity relationships (SAR) and the discovery of HS-based inhibitors. Here, we developed 46 aminoglycoside-derived non-native HS mimetics spanning diverse structural and functional group patterns. SAR analysis identified N-acetylation and 6-O-sulfation as key determinants of HS-FGF2 and HS-VEGF165 interaction modulation. Compound 8, synthesized in two steps, competitively disrupted heparin binding to FGF2 (IC50 = 0.23 μM), FGFR1 (IC50 = 0.17 μM), and VEGF165 (IC50 = 0.66 μM), with >140-fold FGF2/FGF4 selectivity and substantially greater potency than native HS pentasaccharide fondaparinux. In NIH3T3 fibroblasts, compound 8 selectively reduced FGF2-induced proliferation in a dose-dependent manner without measurable cytotoxicity, highlighting aminoglycoside-derived HS mimetics as synthetically accessible platforms for modulating growth factor signaling.

Thrombotic events (TEs) occur in up to 40% of patients with vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic (VEXAS) syndrome, but data on its clinical-genomics features and anticoagulation strategies are limited. To gain more insight into this, we conducted a two-step study evaluating the prevalence and outcome of TE in VEXAS. First, among 1086 patients followed for TEs, 198 were men aged >40 years with unprovoked thrombosis and no known thrombophilia; 21 also had at least one VEXAS-compatible feature and underwent UBA1 exon 3 testing. No UBA1 mutation was detected in these 21 patients. Next, we leveraged our Italian VEXAS network, and we accrued 87 molecularly confirmed Italian VEXAS cases (median age 70 years). Any history of TE was documented in 43/87 patients (49%), deep vein thrombosis being the most common (71%). Because follow-up varied, incident thrombosis was analyzed using a time-to-first-event framework from molecular VEXAS diagnosis, with death without prior TE treated as a competing event. Among 49 patients without prior/concomitant TE, five developed incident post-diagnosis TE; the 24-month cumulative incidence was 18.3%. Thrombophilia testing revealed a 15% co-occurrence, including heterozygous Factor V Leiden, Factor II G20210A, and anti-cardiolipin antibodies. Treatments comprised direct oral anticoagulants (DOACs) (51%), low molecular weight heparin (LMWH) (28%), Fondaparinux (14%), and vitamin K antagonists (AVKs) (7%). Notably, 27% experienced multiple TEs, of which 22% occurring despite anticoagulation during disease flares. Our findings provide an updated cartography of VEXAS-related TE, suggesting early screening for thrombophilia in these patients to inform both personalized anticoagulation and disease-control strategies.

Fondaparinux synthesis remains challenging because of demanding stereochemical control, protecting group manipulation, and purification of highly functionalized intermediates. We report a 2-naphthylmethyl (Nap) protecting group strategy for an azide-functionalized fondaparinux analogue. Direct C-2 Nap installation, combined with C-6 2-(diphenylphosphinoyl)acetyl (DPPA)-assisted β-glucosylation, streamlined assembly, while Nap-mediated phase behavior enabled 17 of 20 intermediates to be isolated without chromatography. The final analogue showed anti-FXa activity comparable to commercial fondaparinux.

The use of agents to prevent and treat thromboembolism in pregnancy continues to increase, likely a reflection of greater burden of comorbid conditions in pregnant people, increased awareness of venous thromboembolism prevention efforts, and enhanced access to diagnostic testing. For this reason, obstetricians commonly find themselves involved in the management of patients who are receiving anticoagulation during pregnancy. Here, we summarize the features of anticoagulants used in pregnancy. Despite the advent of newer agents, the most common anticoagulant used in pregnancy remains heparin derivatives (primarily the low-molecular-weight forms).

Superficial vein thrombosis (SVT) of the legs is a common disease linked with venous thromboembolism (VTE), with an uncertain recurrence risk. Data on secondary prevention of recurrent or extending SVT and on its natural history are lacking. Mesoglycan (MGY) shows a mild antithrombotic effect and the capacity to repair the endothelial layer, by restoring the integrity of the glycocalyx. This study aimed to evaluate the efficacy and safety of MGY for secondary prevention of VTE after an episode of lower-limb SVT.