Abstract Number: PB2466
Meeting: ISTH 2020 Congress
Background: Pharmacokinetic and pharmacodynamic characteristics indicate that clinical, demographic and pharmacogenetic factors can influence DOAC antithrombotic efficacy.
Aims: To establish the influence of ABCB1 rs4148738 polymorphism on DOAC plasma levels and on bleeding and thromboembolic complications.
Methods: Patients were enrolled in our Anticoagulation Clinic from Sept 2013 to April 2015 within the START Register (Survey on anTicoagulated pAtients RegisTer) (NCT 02219984). The study was approved by the local Ethics Committee and all enrolled patients provided informed consent to blood sampling and testing.
Patients taking DOACs for either venous thromboembolism or atrial fibrillation since at least 7 days were enrolled. Demographic and clinical characteristics were collected at enrollment on a standardized form. Diluted thrombin time was measured for dabigatran and anti-Xa activity for apixaban and rivaroxaban on plasmas obtained from blood samples collected in sodium citrate after one month at trough and at peak, e.g. at 2 hours after the morning dose. DNA was extracted from peripheral leukocytes for detection of rs4148738 ABCB1 – P-glycoprotein (P-gp) (intronic region G>A) polymorphism. Major and clinically relevant bleeding and thromboembolic complications were reported during follow-up.
Results: All DOACs showed a high inter-individual variability for both peak and trough concentrations in the 291 enrolled patients. The ABCB1 gene rs4148738 polymorphism was determined in 142 patients and it influenced peak levels of rivaroxaban 20 mg with lower levels in homozygotes for the minor A allele but not those of apixaban. A non significant effect was observed on dabigatran 150 mg bid peak and trough levels. In subjects on rivaroxaban, the cumulative rate of major bleeding was lower ( 8%) in subjects with AA allele than in subjects (17%) with GA/GG alleles, while thromboembolic complications were similar.
Conclusions: The rs4148738 polymorphism of ABCB1 gene of P-gp can influence rivaroxaban peak and trough levels and bleeding complications.
To cite this abstract in AMA style:Cosmi B, Salomone L, Cini M, Guazzaloca G, Legnani C. The Effect of rs4148738 Polymorphism of ABCB1 on the Plasma Concentrations of Direct Oral Anticoagulants and Bleeding an Thromboembolic Complications [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/the-effect-of-rs4148738-polymorphism-of-abcb1-on-the-plasma-concentrations-of-direct-oral-anticoagulants-and-bleeding-an-thromboembolic-complications/. Accessed March 4, 2024.
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