SHM Converge Scientific Abstract ePoster Gallery-Two Pills Too Powerful: When Cyp2c9 Goes Missing

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This case describes a 77-year-old woman recently diagnosed with atrial fibrillation who was discharged on warfarin after conversion to sinus rhythm. Five days later, she returned to the emergency department with worsening chest discomfort and dyspnea. Her ECG showed atrial fibrillation with rapid ventricular response and a new right bundle branch block. Laboratory testing revealed a markedly elevated PT and INR of 5.6 despite reportedly taking only two warfarin doses.<br /><br />Warfarin was held and she was started on a heparin infusion, but her INR continued to climb on serial testing to 6.9, 12.9, and eventually 14.1. She developed severe coagulopathy with concern for cardiogenic shock and was transferred to the ICU. Reversal was performed with intravenous vitamin K and fresh frozen plasma, which gradually lowered her INR and stabilized her clinically.<br /><br />Workup for other causes of coagulopathy, including DIC testing, PT mixing studies, and factor assays, did not show an inhibitor or consumptive process. Because of the extreme and unexplained warfarin sensitivity, pharmacogenomic testing was obtained. This revealed complete loss of CYP2C9 activity along with a VKORC1 promoter variant, explaining her profound response to minimal warfarin exposure.<br /><br />The key lesson is that a dramatic INR rise after little warfarin exposure should trigger evaluation for drug interactions, liver dysfunction, acute illness, and genetic sensitivity. CYP2C9 and VKORC1 variants account for a substantial portion of warfarin dose variability and can cause dangerous over-anticoagulation even with standard dosing. Recognizing pharmacogenomic causes of warfarin hypersensitivity can improve patient safety and guide future anticoagulation choices.

Asset Subtitle

Alexis L. Giosa

Meta Tag

Author List Alexis L. Giosa, Kailey E. Knopf, Sean M. Muir

Category Clinical Vignettes

Concept Warfarin

Concept International Normalized Ratio

Concept Warfarin-Associated Coagulopathy

Concept Warfarin Metabolism

Concept CYP2C9

Distinguished Non-Finalist

Presenter Organization OhioHealth Riverside Methodist

Presenting Author Alexis L. Giosa

Track Adult

Keywords

warfarin hypersensitivity

atrial fibrillation

elevated INR

CYP2C9 variant

VKORC1 promoter variant

coagulopathy

vitamin K reversal

fresh frozen plasma

pharmacogenomics

anticoagulation safety

Warfarin

International Normalized Ratio

Warfarin-Associated Coagulopathy

Warfarin Metabolism

CYP2C9