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Practical issues with vitamin K antagonists: elevated INRs, low time-in-therapeutic range, and warfarin failure

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Abstract

Millions of patients worldwide are prescribed vitamin K antagonists for a variety of medical conditions annually. Despite widespread and long-standing experience with these medications, medical care providers are often confronted with challenging clinical situations. Vitamin K antagonists have a narrow therapeutic index secondary to intrinsic patient characteristics and extrinsic factors including a propensity for drug–drug interactions. Clinicians are required to titrate doses according to the measured international normalized ratio for each individual, balancing the risk of bleeding with preventing thrombosis. The risk of major bleeding associated with vitamin K antagonists has been reported to range from 1 to 3% per year. This narrative review will provide an overview of the most commonly used vitamin K antagonists and discuss the importance of assessing quality of anticoagulation with respect to clinical outcomes. Practical approaches to managing excessive anticoagulation, variable anticoagulation, and anticoagulation failure will be provided, drawing on evidence where applicable and expert opinion where evidence is limited.

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Abbreviations

VKAs:

Vitamin K antagonists

INR:

International normalized ratio

TTR:

Time-in-therapeutic range

VTE:

Venous thromboembolism

ICH:

Intracranial hemorrhage

RCT:

Randomized controlled trial

CI:

Confidence interval

ASA:

Aspirin

HR:

Hazard ratio

NSAIDs:

Non-steroidal anti-inflammatory agents

PCC:

Prothrombin complex concentrate

FFP:

Fresh frozen plasma

(rFVIIa):

Recombinant factor VIIa

PO:

Oral

IV:

Intravenous

SC:

Subcutaneous

APLAS:

Antiphospholipid antibody syndrome

UFH:

Unfractionated heparin

LMWH:

Low-molecular-weight heparin

IVC:

Inferior vena cava

PE:

Pulmonary embolism

DVT:

Deep vein thrombosis

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Acknowledgments

Dr Crowther is a career investigator of the Heart and Stroke Foundation of Ontario and holds the Leo Pharma Chair in Thromboembolism Research at McMaster University.

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  1. Department of Medicine, McMaster University and St Joseph’s Hospital, Room L301, 50 Charlton Ave East, Hamilton, ON, L8N 4A6, Canada

    Andrea Lee & Mark Crowther

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  1. Andrea Lee
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Correspondence to Mark Crowther.

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Lee, A., Crowther, M. Practical issues with vitamin K antagonists: elevated INRs, low time-in-therapeutic range, and warfarin failure. J Thromb Thrombolysis 31, 249–258 (2011). https://doi.org/10.1007/s11239-011-0555-z

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