2012 American College of Chest Physicians by Kimberly Henricks on February 10, 2012 chestjournal.chestpubs.org Downloaded from e32S Parenteral Anticoagulants bleeding associated with the use of LMWH. One animal study reported a reduction in bleeding with protamine sulfate in a microvascular bleeding model, despite persistent anti-Xa activity.175 Another study demonstrated incomplete attenuation of LMWH- A single case report describes the successful use of recombinant activated factor VII to control bleeding in a postoperative patient with renal failure who was receiving LMWH.177 In animal studies, synthetic protamine variants have been shown to be highly effective in neutralizing the anticoagulant effects of LMWH (including anti-Xa activity) and appear to be less toxic than protamine sulfate.109,178-180 Adenosine triphosphate completely reversed LMWH-induced bleeding related to LMWH in a rat model,181 as did PMX 60056, a salicylamide-derived heparin antago- nist.182 In vitro experiments suggest that an anti- thrombin variant (AT-N135Q-Pro394) may neutralize the anticoagulant effects of heparin derivatives, including LMWH and fondaparinux. These agents are not approved for clinical use. The following approach is recommended in clin- ical situations in which the anticoagulant effect of LMWH needs to be neutralized. If LMWH was given within 8 h, protamine sulfate should be administered in a dose of 1 mg per 100 anti-Xa units of LMWH up to a maximum single dose of 50 mg (1 mg enoxaparin equals approximately 100 anti-Xa units). A second dose of 0.5 mg protamine sulfate per 100 anti-Xa units should be administered if bleeding continues. 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. 