title: Prolonged half-life of argatroban in patients with renal dysfunction and antiphospholipid antibody syndrome being treated for heparin-induced thrombocytopenia.
abstract: Argatroban is a direct thrombin inhibitor approved for the treatment of heparin-induced thrombocytopenia (HIT) type II. Argatroban is predominantly metabolized in the liver. It is widely believed that no dosage adjustment is required in patients with renal insufficiency, making it a preferred agent in patients on renal replacement therapy (Reddy and Grossman, Ann Pharm 2005;39:1601-1605). The elimination half-life of argatroban is approximately 50 min. Lupus anticoagulants can cause baseline elevation of the PTT and hence it is difficult to monitor the effects of anticoagulants such as heparin, lepirudin, or argatroban in patients with antiphospholipid antibody syndrome. Heparin levels may be used as an alternative for heparin monitoring but plasma levels of argatroban are not commercially available. A chromogenic antifactor IIa assay could be useful for monitoring argatroban in the presence of a lupus anticoagulant, but it is not widely available at present. We report a patient with end-stage renal disease, maintained on peritoneal dialysis with HIT, who demonstrated a markedly prolonged half-life when treated with argatroban despite the discontinuation of therapy. This case also demonstrates the lack of guidelines for the monitoring of argatroban therapy in the presence of an underlying lupus anticoagulant.
authors.affiliation: Department of Medicine, SUNY Upstate Medical University, Syracuse, New York, USA. atharu@upstate.edu
authors.forename: Uzma
authors.initials: U
authors.lastname: Athar
authors.forename: Juhi
authors.initials: J
authors.lastname: Husain
authors.forename: Jane
authors.initials: J
authors.lastname: Hudson
authors.forename: Jennie
authors.initials: J
authors.lastname: Lynch
authors.forename: Ajeet
authors.initials: A
authors.lastname: Gajra
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016736:Antiphospholipid Syndrome / Q000150:complications; D001120:Arginine / Q000031:analogs & derivatives; D002760:Cholangiopancreatography, Endoscopic Retrograde; D005260:Female; D006207:Half-Life; D006493:Heparin / Q000009:adverse effects; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications; D008180:Lupus Erythematosus, Systemic / Q000150:complications; D008875:Middle Aged; D010530:Peritoneal Dialysis; D010875:Pipecolic Acids / Q000493:pharmacokinetics*; D013449:Sulfonamides; D013921:Thrombocytopenia / Q000139:chemically induced / Q000188:drug therapy*; D016896:Treatment Outcome; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D010875:Pipecolic Acids; D013449:Sulfonamides; D014859:Warfarin; D006493:Heparin; D001120:Arginine; C031942:argatroban