Freyburger Geneviève, Macouillard Gérard, Khennoufa Karim, Labrouche Sylvie, Molimard Mathieu, Sztark François
aLaboratory of Hematology bDepartment of Anesthesiology cLaboratory of Clinical Pharmacology, Bordeaux University Hospital, Bordeaux, France.
Blood Coagul Fibrinolysis. 2015 Dec;26(8):925-33. doi: 10.1097/MBC.0000000000000371.
The aim of this study was to improve knowledge of what happens in the coagulation of orthopaedic patients under rivaroxaban and apixaban, in order to finalize and cross-validate effective measurement methods and to provide arguments for helping to reference one or the other drug in our central pharmacy. One hundred and two patients undergoing total hip or knee replacement were included. Half of them received rivaroxaban and the other half received apixaban. Blood samples (n = 244 with each drug) were taken at Cmax preoperatively and twice a week, apart from the day of the patient's discharge, when Ctrough concentration was targeted. Routine coagulation parameters, and functional and liquid chromatography tandem mass spectrometry assays for measurement of circulating concentrations were studied. The LC-MS/MS assay and the functional assays carried out in patients under routine conditions were highly correlated, apart from low concentrations (<30 ng/ml), which were affected by the variable individual potential to inhibit the exogenous bovine Xa used in the functional assays. After 1 week of treatment, the drugs differed: Cmax and Ctrough were closer when apixaban was taken twice daily (83 ± 39 and 58 ± 17 ng/ml) than with rivaroxaban taken once a day (113 ± 67 and 13 ± 20 ng/ml). Rivaroxaban had a greater influence on routine coagulation tests and reduced the maximum thrombin concentration more efficiently, as assessed by the thrombin generation test. Although rivaroxaban and apixaban present apparently similar constant rates, they exhibit significant differences in their concentrations and anticoagulant effects when studied ex vivo in orthopedic patients.
本研究的目的是增进对接受利伐沙班和阿哌沙班治疗的骨科患者凝血情况的了解，以便确定并交叉验证有效的测量方法，并为在我们的中心药房选用其中一种药物提供依据。纳入了102例行全髋关节或全膝关节置换术的患者。其中一半接受利伐沙班治疗，另一半接受阿哌沙班治疗。在术前Cmax时以及除患者出院日外每周两次采集血样（每种药物采集244份），出院日采集谷浓度（Ctrough）样本。研究了常规凝血参数以及用于测量循环浓度的功能测定法和液相色谱串联质谱分析法。在常规条件下对患者进行的液相色谱-质谱/质谱测定法和功能测定法高度相关，但低浓度（<30 ng/ml）时除外，低浓度受个体抑制功能测定法中使用的外源性牛Xa的能力差异影响。治疗1周后，两种药物存在差异：每日服用两次阿哌沙班时的Cmax和Ctrough更接近（83±39和58±17 ng/ml），而每日服用一次利伐沙班时为（113±67和13±20 ng/ml）。利伐沙班对常规凝血试验影响更大，通过凝血酶生成试验评估，其降低最大凝血酶浓度的效率更高。尽管利伐沙班和阿哌沙班的恒定速率看似相似，但在骨科患者体外研究中，它们在浓度和抗凝效果方面存在显著差异。
