If LMWH is chosen for patients with an estimated cre- atinine clearance of,30 mL/min, anti-Xa monitoring LMWH in doses adjusted by total body weight.145 For thromboprophylaxis with xed-dose enoxaparin and nadroparin, there is a strong negative correlation between total body weight and anti-Xa levels in obese patients.146-148 Several small prospective trials have examined this issue in patients undergoing bariatric surgery, with inconclusive ndings.149-152 Appropriate dosing of LMWH in patients with severe renal insuf ciency is uncertain. Contempo- rary randomized controlled trials evaluating LMWH ef cacy and safety have generally excluded patients with severe renal insuf ciency, de ned in most studies as a creatinine clearance (CrCl)30 mL/min. With few exceptions,153 pharmacokinetic studies have demonstrated that clearance of the anti-Xa effect of LMWH is highly correlated with CrCl.154 This was also observed in a large study of patients receiving therapeutic-dose enoxaparin for coronary indications, in which a strong linear relationship was reported between CrCl and enoxaparin clearance (R5 0.85, P,.001).141 Of particular concern is the potential for accumulation of anti-Xa activity after multiple therapeutic doses. A linear correlation was shown between CrCl and anti-Xa levels (P,.0005) after multiple therapeutic doses of enoxaparin, with sig- ni cantly increased anti-Xa levels in patients with a CrCl,30 mL/min.155 Accumulation after multiple prophylactic doses appears to occur less frequently, but it is still observed. Thus, after multiple prophy- lactic doses of enoxaparin, anti-Xa clearance was reduced by 39% and drug exposure (area under the curve of anti-Xa activity vs time) was 35% higher in patients with a CrCl,30 mL/min compared with that in patients with a CrCl  30 mL/min.156 The data on accumulation with LMWHs other than enoxaparin is limited. 