1.2 Low-Molecular-Weight Heparins LMWHs are derived from UFH by chemical or enzymatic depolymerization. LMWHs have reduced inhibitory activity against thrombin relative to factor Xa,9,10,109-111 have a more favorable bene t-to-risk ratio than heparin in animal models112,113 and when used to treat VTE,114 and have superior pharmacokinetic 1.2.1 Structure and Mechanism of Action: LMWHs are about one-third the molecular weight of UFH. LMWHs have a mean molecular weight of 4,000 to 5,000 which corresponds to about 15 saccharide units and a range of 2,000 to 9,000. Table 4 shows the various LMWHs approved for use in Europe, Canada, and the United States. Because they are pre- pared using different methods of depolymerization, the various LMWHs differ, at least to some extent, in their pharmacokinetic properties and anticoagulant pro les and in their recommended dosing regimens. Therefore, these drugs are not interchangeable on a unit-for-unit basis. oversulfated chondroitin sulfate induces hypotension by promoting the activation of factor XII and the sub- sequent generation of bradykinin.95 Heparin therapy can also cause elevations of serum transaminases. The increase in transaminases is usually transient and is not associated with an increase in bilirubin; it is presumed to have no clinical The main nonhemorrhagic side effects of heparin are HIT and osteoporosis. HIT (discussed further by Linkins et al32 in this supplement) is caused by IgG subclass, heparin-dependent antibodies. These anti- bodies bind to a conformationally modi ed epitope on platelet factor 4 (PF4). Simultaneous binding of these antibodies to Fc receptors on the platelet sur- face causes platelet activation. Activated platelets shed highly prothrombotic microparticles and are then removed from the circulation causing thrombo- cytopenia. In addition, these activated platelets and microparticles provide a surface onto which coagula- tion factor complexes can assemble to promote thrombin generation. 