Pharmacodynamics, clinical indications, and adverse effects of heparin

Heparins are a heterogenous group of naturally occurring glycosaminoglycans characterized by anticoagulant activity and a wide range of molecular weights (low molecular weight or fractionated heparins evolving within the past two decades). Cofactors for endogenous inhibitors of coagulation (antithrombin III and heparin cofactor II), heparin administration results in a hypocoagulable state. Various platelet activities, including inhibition of activity induced by platelet-derived growth factors on vascular smooth muscle, also have been noted. Divorced of anticoagulant nature, novel applications may include a role in atherosclerosis prevention, acceleration of collateral coronary as well as peripheral circulation (i.e., angiogenesis), and continued (chronic) post-myocardial infarction therapy. Established indications include treatment of various thrombotic diseases, unstable angina, and thrombosis chemoprophylaxis in medical/surgical patients. The antithrombotic potential of the heparins is used also in thrombosis management related to extracorporeal circulatory assistance or dialysis devices. Heparin's therapeutic potential in the postphlebitic syndrome as well as in acute treatment of myocardial infarction (primarily and adjunctively with various thrombolytic agents) continues to undergo evaluation; however, early data review shows favorable trends for its inclusion in situations that favor thrombus generation (e.g., anterior myocardial infarction). Although associated with thrombocytopenia or hypertransaminasemia, the heparins are relatively well tolerated. In a small subset of patients, a severe thrombocytopenia may ensue, which generally resolves on medication withdrawal. As this class of glycosaminoglycans becomes better characterized, new indications may emerge for both native and the newer fractionated heparins.