Malabsorption-Associated Warfarin Resistance
Malabsorption-Associated Warfarin Resistance
Purpose. A case of malabsorption-associated warfarin resistance is reported.
Summary. A 42-year-old, 111-kg, Caucasian man arrived at the emergency department with atypical pleuritic chest pain. The chest pain was associated with shortness of breath, diaphoresis, nausea, vomiting, and tachycardia. The patient's medical history was significant for multiple episodes of deep venous thrombosis (DVT) in the left upper extremity and both lower extremities, a right above-the-knee amputation due to complications of a previous DVT, insertion of a vena cava filter, pulmonary embolism (PE), asthma, hypertension, and multiple myocardial infarctions. During admission, he was diagnosed presumptively with PE. All potential causes of interference with warfarin absorption were investigated and ruled out. I.V. warfarin therapy at a conventional initial dosage of 5 mg once daily was started on hospital day 2. The International Normalized Ratio (INR) reached the therapeutic range after increasing the i.v. warfarin dosage to 7.5 mg once daily on hospital day 6. The ability to obtain a therapeutic INR on a relatively low dosage of i.v. warfarin but not high dosages of oral warfarin strongly suggests an inherent warfarin malabsorption defect in this patient.
Conclusion. A 42-year-old man with a history of recurrent thromboembolisms demonstrated resistance to oral warfarin therapy due to warfarin malabsorption.
Warfarin sodium is the only anticoagulant available for oral administration in the United States and is indicated for the prevention and treatment of thromboembolic disorders and embolic complications arising from atrial fibrillation or cardiac valve replacement. Warfarin is 100% bioavailable after oral administration, and its absorption is complete 60–90 minutes after administration.
Due to large interpatient variability in dose response, a narrow therapeutic range, and multiple drug and food interactions, close monitoring is mandatory during the initiation of and long-term maintenance therapy with warfarin. For most indications, the recommended therapeutic target International Normalized Ratio (INR) is between 2 and 3.
In the following case report, we describe a patient unable to attain a therapeutic INR within the target range of 2–3 during administration of unusually high daily oral doses of warfarin. Therapeutic INR levels were obtained only after daily administration of a lower, typical, dose of an i.v. formulation of warfarin sodium.
A Pubmed search of the medical literature using the search terms warfarin resistance and warfarin malabsorption yielded only four case reports documenting warfarin resistance due to malabsorption (Table 1). We describe a fifth case, the first case in a male patient, of warfarin malabsorption.
Abstract and Introduction
Abstract
Purpose. A case of malabsorption-associated warfarin resistance is reported.
Summary. A 42-year-old, 111-kg, Caucasian man arrived at the emergency department with atypical pleuritic chest pain. The chest pain was associated with shortness of breath, diaphoresis, nausea, vomiting, and tachycardia. The patient's medical history was significant for multiple episodes of deep venous thrombosis (DVT) in the left upper extremity and both lower extremities, a right above-the-knee amputation due to complications of a previous DVT, insertion of a vena cava filter, pulmonary embolism (PE), asthma, hypertension, and multiple myocardial infarctions. During admission, he was diagnosed presumptively with PE. All potential causes of interference with warfarin absorption were investigated and ruled out. I.V. warfarin therapy at a conventional initial dosage of 5 mg once daily was started on hospital day 2. The International Normalized Ratio (INR) reached the therapeutic range after increasing the i.v. warfarin dosage to 7.5 mg once daily on hospital day 6. The ability to obtain a therapeutic INR on a relatively low dosage of i.v. warfarin but not high dosages of oral warfarin strongly suggests an inherent warfarin malabsorption defect in this patient.
Conclusion. A 42-year-old man with a history of recurrent thromboembolisms demonstrated resistance to oral warfarin therapy due to warfarin malabsorption.
Introduction
Warfarin sodium is the only anticoagulant available for oral administration in the United States and is indicated for the prevention and treatment of thromboembolic disorders and embolic complications arising from atrial fibrillation or cardiac valve replacement. Warfarin is 100% bioavailable after oral administration, and its absorption is complete 60–90 minutes after administration.
Due to large interpatient variability in dose response, a narrow therapeutic range, and multiple drug and food interactions, close monitoring is mandatory during the initiation of and long-term maintenance therapy with warfarin. For most indications, the recommended therapeutic target International Normalized Ratio (INR) is between 2 and 3.
In the following case report, we describe a patient unable to attain a therapeutic INR within the target range of 2–3 during administration of unusually high daily oral doses of warfarin. Therapeutic INR levels were obtained only after daily administration of a lower, typical, dose of an i.v. formulation of warfarin sodium.
A Pubmed search of the medical literature using the search terms warfarin resistance and warfarin malabsorption yielded only four case reports documenting warfarin resistance due to malabsorption (Table 1). We describe a fifth case, the first case in a male patient, of warfarin malabsorption.
