A Case of Unexplained Warfarin Resistance: A Case Report and Literature Review

Maryam Favaedi; Yeganeh Pasebani; Ali Kabiri; Ali Rafati; Somayeh Jalali; Azam Kiani; Ronak Ahmadi; Aghdas Shadmehr; Aram Amirmazloomi; Zahra Khajali

doi:10.18502/jthc.v18i4.14831

Maryam Favaedi Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.
Yeganeh Pasebani Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.
Ali Kabiri School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Ali Rafati Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.
Somayeh Jalali Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.
Azam Kiani Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.
Ronak Ahmadi Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.
Aghdas Shadmehr Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.
Aram Amirmazloomi School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Zahra Khajali Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.

DOI: https://doi.org/10.18502/jthc.v18i4.14831

Keywords: Warfarin; Coumarin resistance; Vitamin K; Genetic testing

Abstract

Adjusting the exact warfarin dose has always been challenging since it has a narrow therapeutic window. Numerous factors, including poor drug compliance, drug-drug interactions, and malabsorption syndromes, affect the warfarin plasma concentration, leading to oversensitivity or resistance to warfarin. Patients who need more than 15 mg/d of warfarin for maintained anticoagulant effects are considered warfarin resistant.

We describe a 62-year-old man referred to our center with bruising on his feet in June 2021. The patient had a history of valve replacement (mechanical prosthetic valves in 2013), hypothyroidism, and atrial fibrillation. He presented with warfarin resistance (first noticed in 2013) and did not reach the desired warfarin therapeutic effect despite receiving 60 mg of warfarin daily.

Upon admission, the patient was on warfarin (100 mg/d) with an international normalized ratio (INR) of 1.5. He underwent laboratory and molecular genetic tests, which showed no mutation in the CYP2C9 and VKORC1, the genes associated with warfarin resistance.

A stepwise diagnosis is required to identify the underlying cause. Assessing the patient’s compliance, drug history, dietary habits, malabsorption diseases, and genetics may be necessary. We evaluated these possible reasons for resistance and found no correlation. The patient’s warfarin intake was monitored closely to reach the INR therapeutic target of 3-3.5. He decided to leave the hospital with personal consent. He was discharged with a cardiologist referral and 24 warfarin tablets daily (120 mg/d) with an INR of 1.8. The patient was followed up 6 months and 2 years after discharge and was on the same daily dose of warfarin as at discharge, with no complications.