Patients assigned to IV heparin had a signi cantly lower rate of recurrence than those given subcutaneous heparin, presumably as a result of reduced availability of the subcutaneously admin- istered heparin. A study of 400 consecutive patients with acute pulmonary embolism further highlights the importance of early, aggressive therapy: Patients who achieved a therapeutic aPTT in,24 h also had lower in-hospital and 30-day mortality rates compared with those who did not.50 Raschke et al49 randomized patients to receive heparin in xed doses (5,000-unit bolus followed by 1,000 units/h by infusion) or adjusted doses using a Figure 3. Low doses of heparin clear rapidly from plasma through a saturable (cellular) mechanism and the slower, nonsaturable, dose-independent mechanism of renal clearance. Very high doses of heparin are cleared predominantly through the slower nonsatu- rable mechanism of clearance. t1/25half-life. (Reprinted with permission from CHEST.7) Figure 4. As heparin enters the circulation, it binds to heparin- binding proteins (ie, other plasma proteins), endothelial cells, macrophages, and ATIII. Only heparin with the high-af nity pentasaccharide binds to ATIII, but binding to other proteins and to cells is nonspeci c and occurs independently of the ATIII binding site. See Figure 1 legend for expansion of abbreviation. (Reprinted with permission from CHEST.7) 2012 American College of Chest Physicians by Kimberly Henricks on February 10, 2012 chestjournal.chestpubs.org Downloaded from e28S Parenteral Anticoagulants least in part, greater variation in the results of anti-Xa assays than in the aPTT results.84 Therefore, more research is needed to identify the optimal approach for monitoring unfractionated heparin (UFH) therapy. The therapeutic range of heparin for coronary indica- tions is unknown, but is likely to correspond to heparin levels that are about 10% lower than those used for treatment of patients with VTE. 