- Heparin is a naturally occurring, highly sulfated glycosaminoglycan (GAG) that plays a central role in anticoagulation and the regulation of blood clotting.
- It is composed of repeating disaccharide units of iduronic acid (or glucuronic acid) and glucosamine, which are variably sulfated, giving the molecule a very high negative charge density. This unique structure allows heparin to interact strongly with a wide range of proteins, particularly those involved in blood coagulation, making it one of the most widely used and clinically significant polysaccharides in medicine.
- Biologically, heparin is stored in mast cells and released during immune and inflammatory responses, where it helps regulate clot formation, vascular permeability, and cellular signaling. Its primary pharmacological activity, however, lies in its ability to potentiate the action of antithrombin III, a natural inhibitor of thrombin and other clotting factors, such as factor Xa. By accelerating the inhibition of these enzymes, heparin prevents the formation of fibrin clots, thereby acting as a powerful anticoagulant.
- Clinically, heparin has been indispensable for decades in the prevention and treatment of thromboembolic disorders, including deep vein thrombosis (DVT), pulmonary embolism, and myocardial infarction. It is also routinely used in surgical procedures, dialysis, and blood transfusions to prevent clot formation in extracorporeal circuits. There are different formulations of heparin: unfractionated heparin (UFH), which is a mixture of polysaccharide chains of varying lengths, and low-molecular-weight heparins (LMWHs), which are derived by depolymerizing UFH into shorter chains. LMWHs (e.g., enoxaparin, dalteparin) offer improved pharmacokinetics, more predictable dose responses, and reduced risk of side effects compared to UFH.
- One of the main clinical challenges with heparin therapy is the risk of heparin-induced thrombocytopenia (HIT), an immune-mediated condition where antibodies form against heparin-platelet factor 4 complexes, leading paradoxically to increased clotting risk. Careful monitoring of platelet counts and the use of alternative anticoagulants in affected patients are therefore essential. Additionally, bleeding remains the most common adverse effect, requiring precise dosing and, when necessary, reversal with protamine sulfate.
- Beyond its anticoagulant role, research has revealed that heparin interacts with numerous growth factors, chemokines, and adhesion molecules, implicating it in processes such as angiogenesis, inflammation, and cancer metastasis. This has spurred interest in non-anticoagulant heparin derivatives for potential therapeutic use in cancer, viral infections, and inflammatory diseases. Furthermore, synthetic and biosynthetic efforts to produce heparin analogs aim to improve safety, consistency, and supply, given that clinical heparin is traditionally extracted from porcine intestinal mucosa.
