The need for an adapted initiation nomogram during Fiix prothrombin time monitoring of warfarin

  • Pall T. OnundarsonEmail author
  • Brynja R. Gudmundsdottir


The new Fiix prothrombin time (Fiix-PT) and its derived Fiix-normalized ratio (Fiix-NR) is affected only by reductions in coagulation factors (F) II and X, the two factors responsible for the antithrombotic effect of vitamin K antagonists (VKA). Due to insensitivity to reductions in the short half-life FVII, the Fiix-NR rises later than standard PT-INR during warfarin initiation. To describe a warfarin initiation nomogram adapted for monitoring with Fiix-NR, anticoagulation development was assessed during use of standard PT-INR based initiation nomogram and after adapting the initiation nomogram for Fiix-NR monitoring. Normalized ratios were retrospectively assessed in consecutive warfarin naïve patients during their first 60 days of warfarin intake for one year prior to (PT-INR period) and for one year after replacing the PT-INR with the Fiix-NR (Fiix-NR period). The INR target was NR 2.0–3.0. We evaluated 160 patients monitored with PT-INR and dosed with the PT-nomogram, 57 monitored with Fiix-INR but dosed with PT-nomogram, and 163 Fiix-NR monitored patients dosed using a new Fiix nomogram. Mean PT-INR over 2.0 was reached on day 7 during the PT-period and remained around 2.5 thereafter. When the PT-nomogram continued in use during Fiix-monitoring significantly more patients became overanticoagulated during days 11–29. After the nomogram was modified to respond to rising Fiix-NR with larger initial dose reduction, the mean Fiix-NR reached over 2 on day 8–9 and remained around 2.5 thereafter. When warfarin is monitored with Fiix-NR, an adjusted dosing nomogram should be used during initiation to prevent early overanticoagulation.



To the anticoagulation center management staff: Gunnhildur Magnusdottir R.N., Tinna Halldorsdottir R.N., Alma Bjornsdottir R.N. and Erna Valdimarsdottir R.N. and coagulation laboratory staff: Kristin A. Einarsdottir B.S., Loic Letertre B.S. and Oddny Olafsdottir B.S.

Compliance with ethical standards

Conflict of interest

Pall T. Onundarson and Brynja R. Gudmundsdottir are the co-inventors of the Fiix prothrombin time. Together with the University of Iceland and the Landspital National University Hospital they are owners of Fiix Diagnostics LLC which holds a patent for the Fiix-PT.

Ethical approval

The study was approved by the Landspitali University Hospital science ethics committee (25/2017) and followed the guidelines of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

Informed consent was not obtained as this was a retrospective analysis approved by the hospital ethical committee which waives the need for consent for this type of non-interventional retrospective study.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Landspitali National University Hospital of IcelandReykjavíkIceland
  2. 2.Faculty of MedicineUniversity of IcelandReykjavíkIceland

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