Key result
Warfarin INR > 5 linked to ~5.7-fold higher risk of major bleeding.
Why the study?
Warfarin has a narrow therapeutic index, and drug-drug and drug-disease interactions commonly precipitate INR prolongation associated with clinically significant bleeding, morbidity, and mortality. This study evaluated the association between warfarin-drug interactions and INR prolongation (INR > 5) in a tertiary-care emergency department setting.
What is the clinical impact of warfarin–drug interactions and patient risk factors on severe INR prolongation (INR > 5) and bleeding outcomes in adult patients presenting to a tertiary-care emergency department?
Observational (n=114)
No
What is the clinical impact of warfarin–drug interactions and patient risk factors on severe INR prolongation (INR > 5) and bleeding outcomes in adult patients presenting to a tertiary-care emergency department?
In elderly patients on warfarin presenting to the emergency department with INR prolongation, drug interactions—primarily with antibiotics and analgesics—account for 38.7% of events and 44.2% of bleeding episodes, with an INR > 5 strongly predicting major bleeding.
Alerts clinicians to heightened INR monitoring in elderly warfarin users with TIA/stroke history; extends risk data but leaves open prospective validation.
Background: Warfarin is a vitamin K antagonist anticoagulant that is classified as a high-alert medication with a narrow therapeutic index, requiring close monitoring of the international normalized ratio (INR). Excess anticoagulation leading to INR prolongation is associated with clinically significant bleeding, increased morbidity and mortality. 1,2 Drug–drug and drug–disease interactions are among the most common precipitating factors for INR prolongation. This study aimed to evaluate the association between warfarin–drug interactions and INR prolongation (INR > 5) in a tertiary-care emergency department setting. Methods: A retrospective observational study was conducted in the emergency department of Siriraj Hospital, a tertiary-care university hospital, between 1 January 2007 and 31 December 2024. Data were extracted from electronic medical records and analyzed using descriptive statistics, chi-square tests, and logistic regression analyzes Results: A total of 114 patients with INR prolongation were identified, accounting for 124 clinical events (0.79%). The median age was 74 years. Atrial fibrillation (65.8%) and transient ischemic attack (TIA)/stroke (27.2%) were the most common indications for warfarin therapy. Warfarin–drug interactions accounted for 38.7% of INR prolongation events, followed by warfarin–disease interactions (25.0%). Antibiotics and analgesics were the most frequent interacting drug classes. A history of TIA or stroke was significantly associated with an INR > 5 (OR 2.43; 95% CI 1.06–5.57; p = 0.04). Bleeding occurred in 41.9% of events, with warfarin–drug interactions being the leading cause. Most patients (92.3%) recovered after management; however, death occurred in 7.7% of patients. Conclusion: Warfarin–drug interactions, particularly with antibiotics, are a major contributor to INR prolongation and bleeding in elderly patients presenting to the emergency department. Patients with a history of TIA or stroke represent a high-risk subgroup that requires enhanced pharmacovigilance. Proactive INR monitoring, timely dose adjustment, and systematic medication review are essential strategies to reduce adverse outcomes in real-world practice.
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Lertvipapath et al. (2026) conducted an observational in INR prolongation in patients receiving warfarin therapy (n=114). Warfarin-drug interactions and clinical risk factors (e.g., history of TIA/stroke) vs. INR 4 to <5 or absence of risk factor was evaluated on Major bleeding (ACC criteria) associated with severe INR prolongation (INR > 5 vs INR 4 to <5) (OR 5.73, 95% CI 1.46-22.51, p=0.008). Warfarin-drug interactions caused 38.7% of INR prolongations and 44.2% of bleeding events, while an INR > 5 significantly increased major bleeding risk (OR 5.73; 95% CI 1.46-22.51; p=0.008).
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