Pharmacogenetic aspects of dabigatran administration for the prevention of venous thromboembolic complications in patients after orthopedic surgery: clinical cases

Background. The effectiveness and safety of dabigatran for venous thromboembolism (VTE) prophylaxis show significant interindividual variability, partially attributed to pharmacogenetic factors.

Objective. To evaluate the influence of ABCB1 (rs1045642, rs4148738) and CES1 (rs2244613) gene polymorphisms on dabigatran pharmacokinetics and clinical outcomes in patients after orthopedic surgery.

Methods. The study included 60 patients who received dabigatran etexilate (220 mg/day) after total knee arthroplasty. Genotyping was performed by real-time PCR, and dabigatran plasma concentrations were measured by HPLC-MS/MS. Clinical outcomes (VTE, bleeding) were monitored.

Results. The ABCB1 3435TT genotype was associated with higher dabigatran concentrations and an increased bleeding risk, while the CES1 rs2244613 CC genotype correlated with lower concentrations and a higher thrombotic risk. A combination of ABCB1 (CC and TT) and CES1 (AA) genotypes demonstrated optimal efficacy and safety. Heterozygous carriage of all three polymorphisms had an unpredictable effect. A case of severe bleeding due to drug-drug interaction was described.

Conclusion. Genetic polymorphisms of ABCB1 and CES1 significantly influence dabigatran exposure and the risk of complications. Preemptive genotyping could personalize anticoagulant therapy to improve its safety and efficacy in post-operative patients.

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