title: INR vs. thrombin generation assays for guiding VKA reversal: a retrospective comparison.
abstract: BACKGROUND
  Prothrombin complex concentrate (PCC) is used to reverse vitamin K antagonist (VKA)-induced anticoagulation. Prothrombin time-derived international normalized ratio (INR) measurements are widely used in determining the required PCC dose, but this approach requires reappraisal. The aim of the present study was to determine the added value of the thrombin generation assay (TGA) compared with the INR in guidance of VKA reversal by PCC.
  
  
  METHODS
  In an open, observational study, INR and TGA measurements were carried out on plasma samples from phenprocoumon-treated patients receiving VKA reversal. Following both analytical methods, PCC dosing correlates were calculated and compared retrospectively. Alternatively, in vitro PCC spiking experiments were performed.
  
  
  RESULTS
  As expected, an exponential relationship between PCC dose and INR was found. For the TGA parameters peak thrombin and endogenous thrombin potential (ETP), however, this relationship was found to be linear throughout the full therapeutic range. Additional computational analysis showed a positive correlation (r²=0.7) between the initial INR and PCC dose required for a target INR of 2.1, which was completely lost at a lower target INR. In contrast, a positive correlation (r²=0.8) between initial ETP as well as peak height and PCC dose required to obtain parameter normalization was found. These correlates appeared useful for calculating PCC dose.
  
  
  CONCLUSIONS
  Our results support the current debate questioning the rationale for the use of the INR in the management of anticoagulation by VKA. Compared with INR, TGA-based calculations may enable a more accurate PCC dosing regimen for patients requiring VKA reversal.
authors.forename: Robert
authors.initials: R
authors.lastname: Herpers
authors.forename: André P
authors.initials: AP
authors.lastname: van Rossum
authors.forename: Rachel T
authors.initials: RT
authors.lastname: van Beem
authors.forename: W Margot
authors.initials: WM
authors.lastname: Michel
authors.forename: Viola J F
authors.initials: VJ
authors.lastname: Strijbis
authors.forename: Paul F W
authors.initials: PF
authors.lastname: Strengers
authors.forename: Ad
authors.initials: A
authors.lastname: Castel
authors.forename: Herm Jan M
authors.initials: HJ
authors.lastname: Brinkman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000494:pharmacology*; D001780:Blood Coagulation Tests; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013917:Thrombin / Q000096:biosynthesis* / Q000187:drug effects; D013918:Thrombin Time; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: D000925:Anticoagulants; D014812:Vitamin K; D013917:Thrombin