Smaller doses of protamine sulfate can be given if the time since LMWH administration is longer than 8 h. 1.2.6 Nonhemorrhagic Complications: The fre- quency of HIT is threefold lower with LMWHs than with heparin.124 This re ects the fact that the interac- tion of heparin with PF4 is chain length-dependent. Although binding to PF4 is reduced, LMWHs can form complexes with PF4 that are capable of binding HIT antibodies. Consequently, in patients with HIT antibodies, there is cross-reactivity with LMWH (Linkins et al).32 The risk of osteoporosis is lower with LMWH than with heparin. Likely, this re ects the lower af nity of LMWH for osteoclasts and osteoblasts. Monreal and associates183 compared the effects of heparin and LMWH on bone loss in rats and demonstrated that although both produced bone loss, the osteopenic effect was greater with heparin than LMWH. In con- trast, using different measures of bone loss, M tzsch and associates184 reported that, at similar anti-factor Xa activities, the effects of LMWH and UFH on exper- imental bone loss were similar. Shaughnessy and col- leagues reported that heparin and LMWH both and/or dose reduction should be considered to ensure that there is no accumulation. In the case of enox- aparin, dose reduction may be used in patients with CrCl,30 mL/min. The recommended treatment dose of enoxaparin for patients with a CrCl,30 mL/min who have acute coronary syndromes or VTE is 50% of the usual dose (ie, 1 mg/kg once daily). No speci c recommendations have been made for other LMWH preparations. When given in prophylactic doses, LMWH has not been shown to increase the risk of bleeding complica- tions, irrespective of the degree of impairment of renal function. 