ISTH Congress Abstracts

Official abstracts site for the ISTH Congress

MENU 
  • Home
  • Congress Archive
    • ISTH 2022 Congress
    • ISTH 2021 Congress
    • ISTH 2020 Congress
  • Resources
  • Search

Warfarin Resistance Is Rare but Has Heterogeneous Origin in an Anticoagulation Clinic Population

R. Peck1, K. Burley1, L. FitzGibbon1, C. Doherty2, S. Bacon3, R. Thorne2, A. Mumford1

1University of Bristol, Bristol, United Kingdom, 2University Hospital NHS Foundation Trust, Bristol, United Kingdom, 3North Bristol NHS Trust, Bristol, United Kingdom

Abstract Number: PB0541

Meeting: ISTH 2021 Congress

Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Clinical

Background: Warfarin remains an essential anticoagulant for some patients with high thrombotic risk and requires meticulous dose monitoring.

Aims: We performed a snapshot survey of 2,093 patients in the warfarin clinics at two UK hospitals in January 2021 to investigate the prevalence and aetiology of high warfarin dose requirement.

Methods: In both clinics, venous blood INRs were determined using Innovin thromboplastin and Sysmex CA1500 coagulometers. Warfarin dosing was based on RAID or DAWN algorithms.

Results: The median daily warfarin dose was 4.9 mg (range 0.64-100mg). Five (0.24%) patients had warfarin resistance (WR; warfarin dose >25 mg/day). Four of these cases (recurrent thrombosis n=3; mechanical heart valve=1) initially achieved stable therapeutic anticoagulation with warfarin <10mg/day but then required escalating doses to achieve target INR. Plasma warfarin levels were all within therapeutic range of 0.7-2.3 mg/l indicating acquired pharmacokinetic WR. In two cases, this could be linked to established interacting co-medications.  
The remaining case was a 43-year-old male who required anticoagulation after mitral valve repair. INR-guided warfarin dosing rapidly escalated to 35 mg/day at which point the INR was 1.3. Despite this sub-therapeutic INR, the plasma warfarin level was 3.03 mg/l indicating pharmacodynamic WR. Analysis of VKORC1 that encodes the warfarin target Vitamin K epoxide reductase subunit 1 (VKORC1) revealed the heterozygous missense c.85G>T variant predictive of a p.Val29Leu substitution. This likely disrupts VKORC1 warfarin binding interface I (Leu22-Val29) and was shown by others in a cell line model to increase the warfarin IC50 by more than five-fold. c.85G>T is one of 26 missense variants in VKORC1 previously associated with WR in humans, but which do not diminish VKORC1 function in the Vitamin K pathway.

Conclusions: Our findings indicate that WR remains a rare phenotype but has heterogeneous origin. We highlight the utility of measuring plasma warfarin level and VKORC1 genetic testing to assist diagnosis.  

To cite this abstract in AMA style:

Peck R, Burley K, FitzGibbon L, Doherty C, Bacon S, Thorne R, Mumford A. Warfarin Resistance Is Rare but Has Heterogeneous Origin in an Anticoagulation Clinic Population [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/warfarin-resistance-is-rare-but-has-heterogeneous-origin-in-an-anticoagulation-clinic-population/. Accessed October 1, 2023.

« Back to ISTH 2021 Congress

ISTH Congress Abstracts - https://abstracts.isth.org/abstract/warfarin-resistance-is-rare-but-has-heterogeneous-origin-in-an-anticoagulation-clinic-population/

Simple Search

Supported By:

Takeda logo

ISTH 2022 Congress site

Visit the official web site for the ISTH 2022 Virtual Congress ยป

  • Help & Support
  • About Us
  • Cookies & Privacy
  • Wiley Job Network
  • Terms & Conditions
  • Advertisers & Agents
Copyright © 2023 John Wiley & Sons, Inc. All Rights Reserved.
Wiley