Fondaparinux does not bind to protamine sulfate, the antidote for heparin. If uncontrollable bleeding occurs with fondaparinux, recombinant factor VIIa may be effective.202 1.3.4 Nonhemorrhagic Side Effects: Fondaparinux has low af nity for PF4 and does not cross-react with HIT antibodies.203 Although there have been isolated case reports of HIT associated with the use of fonda- parinux204,205 and reports of HIT antibodies without thrombocytopenia in patients given prophylaxis with fondaparinux,206 numerous case reports and case series suggest that this agent can be used to treat patients with HIT.207 This issue is further discussed in the article on HIT by Linkins et al32 in this supple- ment and has been summarized by Blackmer et al.208 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 e35S drug accumulates rapidly in patients with renal insuf- ciency. The dose of hirudin must be reduced when the CrCL is,60 mL/min, and the drug is contraindi- cated in patients with renal failure.216 In a retro- spective observational analysis of 181 patients with con rmed HIT who were treated with lepirudin at a mean dose of 0.06 mg/kg/h for a median treatment duration of 7.7 days, 13.8% suffered a thrombotic event and 20.4% suffered major hemorrhage. The Antibodies against hirudin develop in up to 40% of patients treated with lepirudin. Although most of these antibodies have no clinical impact, some can prolong the plasma half-life of lepirudin, resulting in drug accumulation. In addition, anaphylaxis can occur if patients with antibodies are re-exposed to hirudin. Consequently, an alternative anticoagulant should be considered in patients with HIT who have previously been treated with hirudin. 