Case Reports
Tuesday, November 14, 2023
08:30 AM–10:00 AM
Abstract
Introduction: Warfarin is the most widely used oral anticoagulant; nevertheless, dosing of warfarin is problematic for clinicians worldwide. Inter-individual variability in response to warfarin is attributed to genetic as well as non-genetic factors. Pharmacogenomics studies have identified variants in CYP2C9 and VKORC1 genes as significant predictors of warfarin dose, however, phenotypes of rare variants are not well characterized.
Case:We report a case of hyper-responsiveness to warfarin in a 22-year-old outpatient with Crohn's disease who presented with a swollen, red, and painful left calf. Deep venous thrombosis (DVT) in the left lower extremity was confirmed via ultrasonography, and hence, anticoagulation therapy of heparin and concomitant warfarin was initiated. Warfarin dose of 6.6 mg/day was estimated based on IWPC algorithm. Higher than the expected international normalized ratio (INR) value of 4.5 necessitated the reduction of the warfarin dose, to 5 and eventually to 2.5 mg/day to reach a therapeutic INR value of 2.6. Pharmacogenetic profiling of the VKORC1 -1639G>A and CYP2C9 *2, *3, *4, *5, *8, *14, *20, *24, *26, *33, *40, *41, *42, *43, *45, *46, *55, *62, *63, *66, *68, *72, *73 and *78 revealed a VKORC1-1639GA/CYP2C9*1*46 genotype. The lower catalytic activity of the CYP2C9*46 (A149T) variant was previously reported in in vitro settings.
Discussion: CD per se and concomitant azathioprine are expected to increase warfarin dose requirements in our case patient. Intriguingly, our patient attained high INR at standard dose of warfarin, which could have predisposed him to serious bleeding. Due to the failure of non-genetic factors guided warfarin dose prediction, it was rational to investigate the underlying genetic factors that may elucidate this patient's hyper-responsiveness to a standard dose of warfarin.
Conclusion: This is the first report on a case of warfarin hyper-responsive phenotype of a patient with the heterozygous CYP2C9*1*46 polymorphism.
Presenting Author
Weam Aldiban Ph.DAuthors
Majd Aljamali Ph.D
Damascus University
Yara Altawil MS
Damascus University
Samir Hussein MS
AL Basel Hospital, Homs, Syrian Arab Republic.
Lama Youssef Ph.D
Damascus University