Ing Lorenzini Kuntheavy, Daali Youssef, Fontana Pierre, Desmeules Jules, Samer Caroline
Division of Clinical Pharmacology and Toxicology, University Hospitals of Geneva Geneva, Switzerland.
Division of Angiology and Haemostasis, University Hospitals of Geneva Geneva, Switzerland.
Front Pharmacol. 2016 Dec 19;7:494. doi: 10.3389/fphar.2016.00494. eCollection 2016.
We report a patient who presented a non-ST segment elevation myocardial infarction in the context of severe normocytic hypochromic anemia related to gastrointestinal bleeding, 3 months after switching anticoagulant from the vitamin K antagonist acenocoumarol to the direct oral anticoagulant rivaroxaban. High levels of both anti-Xa activity and rivaroxaban plasma concentrations were measured despite rivaroxaban withdrawal, suggesting reduced elimination/drug clearance. Estimated half-life was 2-3 times longer than usually reported. The patient is a homozygous carrier of variant alleles, which could have participated to reduced elimination of rivaroxaban. Furthermore, CYP3A4/5 phenotyping showed moderately reduced enzyme activity. Drug-drug interaction with simvastatin may have contributed to decreased rivaroxaban elimination. Although in the present case moderate acute renal failure probably played a role, more clinical data are required to elucidate the impact of polymorphism on rivaroxaban pharmacokinetics and bleeding complications.
我们报告了一名患者，该患者在将抗凝剂从维生素K拮抗剂醋硝香豆素转换为直接口服抗凝剂利伐沙班3个月后，因胃肠道出血导致严重正细胞性低色素性贫血，进而出现非ST段抬高型心肌梗死。尽管停用了利伐沙班，但仍检测到高水平的抗Xa活性和利伐沙班血浆浓度，提示消除/药物清除减少。估计半衰期比通常报道的长2至3倍。该患者是变异等位基因的纯合携带者，这可能参与了利伐沙班消除的减少。此外，CYP3A4/5表型显示酶活性中度降低。与辛伐他汀的药物相互作用可能导致利伐沙班消除减少。虽然在本病例中中度急性肾衰竭可能起了作用，但需要更多临床数据来阐明多态性对利伐沙班药代动力学和出血并发症的影响。
