title: Use of subcutaneous lepirudin in an obese surgical intensive care unit patient with heparin resistance.
abstract: OBJECTIVE
  To report the use of subcutaneous lepirudin in an obese patient with heparin resistance.
  
  
  METHODS
  A 34-year-old morbidly obese male (weight 145 kg) presented with hypoxia on postoperative day 1 following a sigmoid colectomy. A continuous unfractionated heparin infusion was started for a suspected pulmonary embolism. Doses were escalated without therapeutic activated partial thromboplastin time (aPTT) response and an antithrombin (AT) level was obtained. The AT level was reported as 78% (reference range 85-120%). Computed tomography angiography ruled out pulmonary embolism and lepirudin 50 mg administered subcutaneously twice daily was started (serum creatinine 1.3 mg/dL) for prevention of venous thromboembolism. The resulting aPTT values were therapeutic (63 and 60 sec, reference range 24-34, therapeutic heparin range 55-85). The dose was adjusted to 25 mg twice daily. aPTT values were 35 and 48 seconds. His serum creatinine increased to 1.6 mg/dL and minor bleeding was noted. The dose was decreased to 25 mg once daily, with resulting aPTT values of 31, 39, and 41 seconds. The patient was discharged to home without development of venous thromboembolism, as confirmed by duplex ultrasonography.
  
  
  CONCLUSIONS
  Commonly administered anticoagulants, such as unfractionated heparin, low-molecular-weight heparins, and fondaparinux, exert their effect by complexing with AT and thrombin (Factor IIa), activating AT and preventing thrombin from exerting coagulation effect. Without AT present, these drugs have little effect on inhibiting the coagulation cascade. Lepirudin is a synthetic irreversible direct thrombin inhibitor and does not rely on AT to exert its anticoagulation action. It can be given subcutaneously and is eliminated primarily by the kidneys. Dosage adjustments for both renal function and obesity need to be considered and aPTT should be monitored.
  
  
  CONCLUSIONS
  In obese patients or those with heparin resistance, subcutaneous lepirudin can be monitored and the regimen adjusted based on aPTT values. Further studies are warranted to maximize efficacy and define dosing.
authors.affiliation: Department of Pharmacy, The Ohio State University Medical Center, Columbus, OH 43210, USA.
authors.forename: Kristin R
authors.initials: KR
authors.lastname: Inman
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Gerlach
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D003422:Critical Care / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D006493:Heparin / Q000627:therapeutic use; D006629:Hirudins / Q000008:administration & dosage; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D009767:Obesity, Morbid; D010314:Partial Thromboplastin Time; D011994:Recombinant Proteins / Q000008:administration & dosage; D054556:Venous Thromboembolism / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D006629:Hirudins; D011994:Recombinant Proteins; D006493:Heparin; C083544:lepirudin