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Anticoagulant Drugs: Vitamin K Antagonists and Direct Oral Anticoagulants01:18

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Warfarin therapy--why one dose does not fit all!

Vrinda Kulkarni, Abhay Bhave, Renuka Kulkarni Munshi

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    Managing warfarin therapy can be challenging due to genetic variations affecting drug response. Pharmacogenomics testing for CYP2C9 and VKORC1 gene mutations helps personalize warfarin dosing for improved patient outcomes.

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    Area of Science:

    • Pharmacogenomics
    • Clinical Pharmacology
    • Thrombosis Management

    Background:

    • Warfarin is a widely used oral anticoagulant for preventing and treating thromboembolic events.
    • Achieving and maintaining a stable therapeutic International Normalized Ratio (INR) with warfarin can be challenging due to inter-individual variability in response.
    • Genetic factors, particularly polymorphisms in CYP2C9 and VKORC1 genes, significantly influence warfarin pharmacokinetics and pharmacodynamics.

    Observation:

    • This case report details an Indian adult female patient with Deep Vein Thrombosis (DVT) who exhibited difficulty in achieving and maintaining target INR on conventional warfarin doses.
    • Pharmacogenomic analysis revealed the patient possessed homozygous mutations in CYP2C9 (*3/*3) and heterozygous mutations in VKORC1 (1639G>A), a genetic double defect.
    • These genetic variations conferred increased sensitivity to warfarin, complicating standard dosing regimens.

    Findings:

    • The patient's homozygous CYP2C9 *3/*3 and heterozygous VKORC1 (1639G>A) polymorphisms resulted in a significantly heightened response to warfarin.
    • Conventional warfarin dosing proved insufficient for therapeutic anticoagulation, necessitating careful dose adjustments.
    • The identified genetic profile explains the challenges in managing this patient's anticoagulation therapy.

    Implications:

    • Pharmacogenomic testing for CYP2C9 and VKORC1 gene variants can identify patients with increased warfarin sensitivity or resistance.
    • Individualized warfarin dosing based on genetic profiles can optimize therapeutic efficacy and minimize the risk of bleeding or thrombosis.
    • Integrating pharmacogenomics into clinical practice can improve the safety and effectiveness of warfarin therapy, especially in genetically diverse populations.