ABSTRACT
Heparin is commonly used for anticoagulation; however, its nonanticoagulant effects such as the
anti-inflammatory and antiproliferative actions have been known for some time. As a poly-
component drug, heparin produces multiple effects at cellular and humoral levels. Its ability to
release and modulate the generation of endogenously active substances has also been known for
many years. Heparin’s interactions with endogenous proteins and vascular cells are also widely
appreciated. The development of low-molecular-weight heparin (LMWH) represents an
improved usage of heparin-derived sulfated polymers with improved pharmacological profiles.
Initially developed for the prophylaxis of deep-vein thrombosis (DVT) , these drugs have found
their applications in thrombotic, cardiovascular, hemodynamic, proliferative, and autoimmune
disorders, to name a few indications. The clinical profiles of intravenous and subcutaneously
administered LMWHs differ from unfractionated heparin (UFH) owing to their biochemical and
pharmacological profiles. Because of their size, the LMWHs exhibit better vascular and cellular
uptake; easy accessibility to the membrane barriers; and are capable of interacting with growth
factors and other cytokines. Clinical trials designed to test the efficacy of these agents in the
prophylaxis and treatment of thrombosis reveal added benefits of these drugs in patients with
cancer, autoimmune diseases, sepsis, and hemodynamic disorders. Experimental investigations
also demonstrated several nonanticoagulant effects of these drugs, paving their way into the
management of nonthrombotic disorders. The LMWHs are now being tested in several clinical
trials for such indications as thrombotic stroke, vascular dementia, inflammatory bowel disease,
malignancy, autoimmune diseases, and bone-marrow-associated vascular disorders. The safety
and efficacy of these drugs in the elderly, in pregnant women, the pediatric population, and
weight-compromised individuals have also been established. Thus, LMWHs will provide not
only an antithrombotic drug group with higher therapeutic index, but will be gradually
developed in expanded indications that may include nonthrombotic diseases.
