- Polysaccharides as anticoagulant agents represent an important class of bioactive macromolecules with significant therapeutic and biomedical potential. The most well-known example is heparin, a highly sulfated glycosaminoglycan widely used in clinical settings for the prevention and treatment of thrombosis. However, in recent decades, attention has expanded to other natural and semi-synthetic polysaccharides—including those derived from marine algae (fucoidan, carrageenan, ulvan), plants (pectins, galactans), fungi (β-glucans), and microbial sources—that exhibit anticoagulant activity. Their structural diversity, variable charge density, and bioavailability make them versatile candidates for modulating blood coagulation pathways in a manner similar to or distinct from heparin.
- The anticoagulant mechanism of polysaccharides generally arises from their ability to interfere with key steps in the coagulation cascade. Sulfated polysaccharides, in particular, exert their activity by mimicking the structure and charge distribution of natural glycosaminoglycans. They bind to plasma proteins such as antithrombin III or heparin cofactor II, enhancing their ability to inhibit coagulation enzymes like thrombin (factor IIa) and factor Xa. Some polysaccharides act directly by prolonging clotting times (activated partial thromboplastin time, prothrombin time, or thrombin time), while others influence platelet aggregation or fibrin polymerization. The degree of sulfation, molecular weight, monosaccharide composition, and branching pattern are critical determinants of anticoagulant potency.
- Among marine-derived polysaccharides, fucoidans from brown algae and carrageenans from red algae have been studied extensively for their anticoagulant potential. Fucoidan, rich in sulfated fucose residues, exhibits strong heparin-like activity and can inhibit thrombin generation. Carrageenans, depending on their sulfation pattern (κ-, ι-, or λ-carrageenan), display variable anticoagulant properties. Similarly, ulvan from green algae, containing sulfated rhamnose and uronic acids, has demonstrated anticoagulant activity through unique interactions with clotting factors. These marine polysaccharides represent sustainable and renewable alternatives to animal-derived anticoagulants, addressing concerns of contamination, immunogenicity, and religious restrictions associated with porcine heparin.
- In biomedical applications, polysaccharide-based anticoagulants are being explored not only as systemic therapies but also as components of biomaterials. Sulfated polysaccharides are incorporated into hemodialysis membranes, vascular graft coatings, and drug delivery systems to reduce thrombosis risk. Their ability to combine anticoagulant function with biocompatibility makes them attractive for wound dressings, tissue engineering scaffolds, and controlled-release systems. Moreover, chemical modifications—such as sulfation, phosphorylation, or carboxymethylation—are used to enhance or tune anticoagulant activity, allowing the design of polysaccharide derivatives with optimized therapeutic properties.
- From a clinical perspective, polysaccharides offer several advantages over conventional anticoagulants. They are generally biodegradable, biocompatible, and less likely to cause severe side effects like heparin-induced thrombocytopenia (HIT). However, challenges remain, including variability in structure depending on the source, difficulties in standardizing extraction and purification, and the need for precise control of molecular weight and sulfation patterns to ensure consistent activity. Toxicity, immunogenicity, and potential interference with other physiological pathways also require careful evaluation in translational studies.
