title: Alternative monitoring of argatroban using plasma-diluted thrombin time.
abstract: OBJECTIVE
  To report a case of heparin-induced thrombocytopenia (HIT) in a patient with concurrent liver dysfunction and a prolonged baseline activated partial thromboplastin time (aPTT) in whom argatroban therapy was monitored with aPTT and a novel plasma-diluted thrombin assay.
  
  
  METHODS
  An 80-year-old man with HIT and liver dysfunction was treated with argatroban, which was initiated at a dose of 0.5 μg/kg/min and gradually decreased to 0.09 μg/kg/min. The patient had a mildly prolonged aPTT at baseline (37.5 seconds). He was concurrently monitored with aPTT, per institution protocol, and plasma-diluted thrombin time. Plasma-diluted thrombin times were consistently lower than aPTTs, but mirrored the trend of the aPTTs. Eleven hours after argatroban was stopped, the aPTT remained elevated (53.9 seconds), while the plasma-diluted thrombin time returned to normal range (26.4 seconds). The patient's therapy was transitioned to warfarin and he had a hospital course with no thrombotic or bleeding complications.
  
  
  CONCLUSIONS
  Plasma-diluted thrombin time is a novel laboratory test consisting of 1 part patient plasma diluted with 3 parts normal plasma. Plasma-diluted thrombin time has been shown to blunt the sensitivity of the thrombin time and may be more accurate for drug monitoring. A MEDLINE search revealed 2 studies using the plasma-diluted thrombin time assay. The first study compared aPTT and plasma-diluted thrombin times in blood samples mixed with argatroban, bivalirudin, or lepirudin at 3 different concentrations. Blood samples contained lupus inhibitors, vitamin k deficiency, or normal baseline aPTTs. The aPTT overestimated drug concentrations in all samples with lupus anticoagulant and vitamin k deficiency, while the plasma-diluted thrombin time correctly estimated drug concentrations in nearly all samples. The second study looked at monitoring dabigatran with plasma-diluted thrombin time and found a linear relationship between the plasma-diluted thrombin time and the dabigatran dose-response curve.
  
  
  CONCLUSIONS
  Plasma-diluted thrombin time may be an alternative for direct thrombin inhibitor monitoring in patients with elevated aPTT values at baseline. Further randomized control trials are needed to determine its applicability in clinical practice.
authors.affiliation: College of Pharmacy, University of Houston, Houston, TX, USA. MAWanat@uh.edu
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Wanat
authors.forename: Sara R
authors.initials: SR
authors.lastname: Hart
authors.forename: David
authors.initials: D
authors.lastname: Putney
authors.forename: Michael G
authors.initials: MG
authors.lastname: Liebl
authors.forename: Wayne
authors.initials: W
authors.lastname: Chandler
mesh_terms: D000369:Aged, 80 and over; D001120:Arginine / Q000031:analogs & derivatives; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D008107:Liver Diseases / Q000097:blood / Q000188:drug therapy; D008297:Male; D010875:Pipecolic Acids / Q000627:therapeutic use*; D013449:Sulfonamides; D013918:Thrombin Time / Q000379:methods*; D013921:Thrombocytopenia / Q000188:drug therapy*
chemical_list: D010875:Pipecolic Acids; D013449:Sulfonamides; D001120:Arginine; C031942:argatroban