Ignoring instead of chasing after coagulation factor VII during warfarin management: an interrupted time series study

Alma R. Oskarsdottir, Brynja R. Gudmundsdottir, Hulda M. Jensdottir, Bjorn Flygenring, Ragnar Palsson, Pall T. Onundarson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

During warfarin management, variability in prothrombin time-based international normalized ratio (PT-INR) is caused, in part, by clinically inconsequential fluctuations in factor VII (FVII). The new factor II and X (Fiix)-prothrombin time (Fiix-PT) and Fiix-normalized ratio (Fiix-NR), unlike PT-INR, are only affected by reduced FII and FX. We assessed the incidence of thromboembolism (TE) and major bleeding (MB) in all 2667 patients on maintenance-phase warfarin managed at our anticoagulation management service during 30 months; 12 months prior to and 18 months after replacing PT-INR monitoring with Fiix-NR monitoring. Months 13 to 18 were predefined as transitional months. Using 2-segmented regression, a breakpoint in the monthly incidence of TE became evident 6 months after test replacement, that was followed by a 56% reduction in incidence (from 2.82% to 1.23% per patient-year; P = .019). Three-segmented regression did not find any significant trend in TE incidence (slope, +0.03) prior to test replacement; however, during months 13 to 18 and 19 to 30, the incidence of TE decreased gradually (slope, −0.12; R2 = 0.20; P = .007). The incidence of MB (2.79% per patient-year) did not differ. Incidence comparison during the 12-month Fiix and PT periods confirmed a statistically significant reduction (55-62%) in TE. Fiix monitoring reduced testing, dose adjustments, and normalized ratio variability and prolonged testing intervals and time in range. We conclude that ignoring FVII during Fiix-NR monitoring in real-world practice stabilizes the anticoagulant effect of warfarin and associates with a major reduction in TEs without increasing bleeding.

Original languageEnglish
Pages (from-to)2745-2755
Number of pages11
JournalBlood
Volume137
Issue number20
DOIs
Publication statusPublished - 20 May 2021

Bibliographical note

Funding text 1
This work was supported by a technology development grant from The Icelandic Research Fund/Technology Development Fund ( www.RANNIS.is ). FII- and FX-deficient plasma was provided free of charge by Hart Biologicals Ltd, Hartlepool, United Kingdom ( www.hartbio.co.uk ).
Funding text 2
The authors thank the Landspitali anticoagulation management service staff (Gunnhildur Magnusdottir, Tinna Halldorsdottir, Alma Bjornsdottir, and Erna Valdimarsdottir) and the coagulation laboratory staff (Kristin A. Einarsdottir, Loic Letertre, and Oddny Olafsdottir), as well as Ubaldo Benitez Hernandez, statistical advisor, Department of Scientific Affairs. This work was supported by a technology development grant from The Icelandic Research Fund/Technology Development Fund (www.RANNIS.is). FII- and FX-deficient plasma was provided free of charge by Hart Biologicals Ltd, Hartlepool, United Kingdom (www.hartbio.co.uk). The funding sources had no role in the study design, data collection, analysis, interpretation of data, writing of the report, or in the decision to submit the article for publication.

Publisher Copyright:
© 2021 American Society of Hematology

Other keywords

  • Blóðfræði
  • Warfarin

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