However, these chains are capable of promoting factor Xa inactivation by AT because this reaction does not require bridging. Because virtually all mole- cules of UFH contain at least 18 saccharide units, heparin has, by de nition, an anti-Xa to anti-IIa ratio of 1:1. In contrast, commercial LMWHs have anti-Xa to anti-IIa ratios between 2:1 and 4:1 depending on their molecular size distribution. At present, there is no evidence that the differences in anti-Xa to anti-IIa ratio among the LMWHs in uence clinical outcomes such as recurrent thrombosis or bleed- ing complications. Numerous randomized clinical Table 5 Biologic Consequences of Reduced Binding of LMWH to Plasma Proteins and Cells Binding Target Biologic Effects Clinical Consequence Thrombin Reduced anti-IIa activity relative to anti-Xa activity Unknown Proteins More predictable anticoagulant response Coagulation monitoring unnecessary Macrophages Cleared through renal mechanism Longer plasma half-life permits once-daily administration Platelets Reduced formation of HIT antibodies Reduced incidence of HIT Osteoblasts Reduced activation of osteoclasts Lower risk of osteopenia HIT5heparin-induced thrombocytopenia. See Table 4 legend for expansion of other abbreviation. 2012 American College of Chest Physicians by Kimberly Henricks on February 10, 2012 chestjournal.chestpubs.org Downloaded from www.chestpubs.org CHEST / 141 / 2 / FEBRUARY, 2012 SUPPLEMENT e31S low as 20 mL/min.159 The apparent difference in tinzaparin clearance in patients with severe renal insuf ciency may re ect metabolism by hepatic mechanisms, possibly due to the higher molecular weight of tinzaparin compared with other LMWHs. Decreased LMWH clearance has been associated with increased bleeding risks in patients with severe renal insuf ciency. Lim and associates160 compared the risk of major bleeding and anti-Xa levels in patients receiving LMWH who had severe renal insuf- ciency (CrCl30 mL/min) with those in patients without renal impairment (CrCl . 30 mL/min). 