1.2.4 Dosing and Monitoring in Special Situations: With enoxaparin, anti-Xa activity is increased to appropriate levels when the drug is administered to obese patients in doses based on total body weight up to a weight of 144 kg.141 The same is true for dalteparin142,143 and tinzaparin144 in patients weighing up to 190 and 165 kg, respectively. In a meta-analysis that included data on 921 patients with a BMI30, there was no excess in the rate of major bleeding over that observed in nonobese patients who received Depolymerization of heparin yields low-molecular weight fragments that exhibit reduced binding to proteins and cells (Table 5). The reduced af nity for proteins and cells explains the anticoagulant, phar- macokinetic, and other biologic differences between heparin and LMWH. Thus, compared with heparin, LMWHs have reduced ability to inactivate thrombin because the smaller fragments cannot bind simulta- neously to AT and thrombin. Reduced binding to plasma proteins other than AT is responsible for the more predictable dose-response relationship of LMWHs.122 Decreased binding to macrophages and endothelial cells explains the longer plasma half-life of LMWH relative to UFH, whereas reduced binding to platelets and PF4 explains the lower incidence of HIT.123,124 Finally, the decreased binding of LMWH to osteoblasts results in less activation of osteoclasts and less bone loss.30,31 Like heparin, LMWHs produce their major anti- coagulant effect by catalyzing AT-mediated inhi- bition of coagulation factors. The pentasaccharide sequence required for binding is found on fewer than one-third of LMWH molecules.14,125 Because only pentasaccharide-containing heparin chains composed of at least 18 saccharide units are of suf cient length to bridge AT to thrombin, 50% to 75% of LMWH chains are too short to catalyze thrombin inhibition. However, these chains are capable of promoting factor Xa inactivation by AT because this reaction does not require bridging. 