Decreased argatroban clearance unaffected by hemodialysis in anasarca.
OBJECTIVE
To report the case of a patient with acute renal failure and anasarca undergoing hemodialysis who demonstrated a prolonged effect of argatroban despite having no hepatic dysfunction.


METHODS
A 54-year-old white woman with a past medical history of St. Jude's prosthetic mitral valve placement was admitted for anasarca secondary to acute renal failure of unknown origin. In order to prevent valve thrombosis and stroke, argatroban was initiated. Despite having no hepatic dysfunction, the patient demonstrated an elevated activated partial thromboplastin time (aPTT) for a prolonged period of time, requiring a significant dose reduction. This suggested reduced clearance of argatroban. Furthermore, this prolonged effect persisted despite hemodialysis.


CONCLUSIONS
Patients with severe renal dysfunction eliminate argatroban at a rate similar to that in healthy volunteers, while those with hepatic disease have a marked decrease in argatroban elimination. Our patient apparently had a reduction in argatroban elimination similar to that in patients with hepatic dysfunction. The few published reports regarding the use of argatroban in patients undergoing hemodialysis generally lack any information regarding variations in plasma concentrations of argatroban, the aPTT, or the type of dialyzer used. The available data, as well as our report, suggest that dosing adjustment during hemodialysis may not be necessary in patients without associated hepatic dysfunction.


CONCLUSIONS
This report suggests that in patients who are fluid-overloaded, the anticoagulant effects of argatroban may be prolonged to a degree similar to that observed in patients with hepatic disease. Our report supports the previously published data that hemodialysis has little, if any, role in increasing argatroban elimination.
de Denus
Simon
S
Philadelphia College of Pharmacy, University of the Sciences in Philadelphia, Philadelphia, PA 19104, USA.
Spinler
Sarah A
SA
D058186:Acute Kidney Injury / Q000150:complications / Q000628:therapy; D001120:Arginine / Q000031:analogs & derivatives; D004487:Edema / Q000209:etiology / Q000378:metabolism*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010875:Pipecolic Acids / Q000493:pharmacokinetics*; D006435:Renal Dialysis; D013449:Sulfonamides; D013917:Thrombin / Q000037:antagonists & inhibitors*; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control
D010875:Pipecolic Acids; D013449:Sulfonamides; D001120:Arginine; D013917:Thrombin; C031942:argatroban