An Expert Report on the Pharmacology and Clinical Use of Heparin

Executive Summary

Heparin is a cornerstone anticoagulant that has been integral to clinical medicine for over eight decades. Identified chemically as a heterogeneous mixture of sulfated glycosaminoglycan polymers, unfractionated heparin (UFH) is a naturally occurring polysaccharide ubiquitously present in mast cells.[1] Its primary therapeutic function is the prevention and treatment of thromboembolic disorders. The drug's mechanism of action is indirect and complex; it exerts its anticoagulant effect by binding to and potentiating the activity of the endogenous plasma protein antithrombin III (ATIII). This heparin-ATIII complex then acts as a powerful inhibitor of several key coagulation cascade enzymes, most notably thrombin (Factor IIa) and activated Factor X (Factor Xa).[1]

The clinical utility of heparin is extensive, spanning a wide array of indications. It is indispensable for the prophylaxis and treatment of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE); for managing atrial fibrillation with systemic embolization; and as an adjunct therapy in acute coronary syndromes.[1] Furthermore, heparin is critical for preventing thrombosis in extracorporeal circuits, a vital application in procedures such as cardiopulmonary bypass surgery, hemodialysis, and blood transfusions.[5]

Despite its efficacy, the use of heparin is accompanied by significant risks. The principal and most frequent adverse effect is hemorrhage, a direct extension of its therapeutic anticoagulant activity that necessitates careful patient selection and monitoring.[4] A more complex and paradoxical complication is Heparin-Induced Thrombocytopenia (HIT), a severe, immune-mediated reaction that, despite causing a drop in platelet count, leads to a profoundly prothrombotic state with a high risk of life-threatening arterial and venous thrombosis.[4]