title: Argatroban and lepirudin requirements in a 6-year-old patient with heparin-induced thrombocytopenia.
abstract: A 6-year-old girl required argatroban at dosages up to 18 mug/kg/minute for treatment of heparin-induced thrombocytopenia (HIT) type 2; however, her activated partial thromboplastin time (aPTT) values remained subtherapeutic. Treatment was converted to lepirudin, which resulted in therapeutic aPTT values, and later to long-term warfarin therapy; no further thromboembolic incidents occurred. The reporting of cases of HIT in prepubertal patients has generally been scarce. Argatroban and lepirudin dosing and pharmacokinetics have not yet been established for young children. The argatroban dosage for this patient exceeded the upper limit of the dose range for adults. Several possible explanations for why argatroban did not illustrate typical first-order pharmacokinetics in this patient are discussed, and the pharmacokinetics and pharmacodynamics of argatroban are compared with those of lepirudin, with special consideration given to the pediatric population.
authors.affiliation: Department of Pharmacy, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. tjohn@partners.org
authors.forename: Tanya E
authors.initials: TE
authors.lastname: John
authors.forename: Robert K
authors.initials: RK
authors.lastname: Hallisey
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives; D002648:Child; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D005260:Female; D006493:Heparin / Q000009:adverse effects*; D006629:Hirudins / Q000493:pharmacokinetics; D006801:Humans; D010314:Partial Thromboplastin Time; D010875:Pipecolic Acids / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000627:therapeutic use; D013449:Sulfonamides; D013921:Thrombocytopenia / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D000925:Anticoagulants; D006629:Hirudins; D010875:Pipecolic Acids; D011994:Recombinant Proteins; D013449:Sulfonamides; D006493:Heparin; D003577:Cytochrome P-450 Enzyme System; D001120:Arginine; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C031942:argatroban; C083544:lepirudin