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利伐沙班与血栓性抗磷脂综合征中抗磷脂抗体的相互作用。

Interactions between rivaroxaban and antiphospholipid antibodies in thrombotic antiphospholipid syndrome.

机构信息

Haemostasis Research Unit, Department of Haematology, University College London, London, UK.

Centre for Rheumatology, Division of Medicine, University College London, London, UK.

出版信息

J Thromb Haemost. 2015 Jul;13(7):1264-73. doi: 10.1111/jth.12917. Epub 2015 May 9.

Abstract

INTRODUCTION

Rivaroxaban can affect lupus anticoagulant (LA) testing and antiphospholipid antibodies (aPL) may interfere with the anticoagulant action of rivaroxaban.

AIMS

To establish the influence of rivaroxaban on LA detection and of aPL on the anticoagulant action of rivaroxaban.

METHODS

Rivaroxaban and 52 IgG preparations (20 LA+ve, 12 LA-ve thrombotic antiphospholipid syndrome [APS] patients, and 20 normal controls [NC]) were spiked into pooled normal plasma (PNP) for relevant studies. LA detection was also studied in APS patients receiving rivaroxaban 20 mg once daily.

RESULTS

In vitro spiking of samples with rivaroxaban showed no false positive LA with Textarin time, Taipan venom time/Ecarin clotting time (TVT/ECT), dilute prothrombin time (dPT) and in-house dilute Russell's viper venom time (DRVVT), but false positives in the majority of NC and LA negative IgG with two commercial DRVVT reagents at 250 ng/mL but not 50 ng/mL rivaroxaban. Ex vivo studies: six LA+ve patients on rivaroxaban remained LA positive with TVT/ECT and DRVVT at peak (162-278 ng/mL) and trough (30-85 ng/mL) rivaroxaban levels. Six LA-ve patients became (apparently) LA+ve with two DRVVT reagents (test/confirm ratio median [confidence interval], 1.6 [1.3-1.8], 1.6 [1.4-1.9]) but not with TVT/ECT at peak rivaroxaban levels, and remained LA-ve with both DRVVT reagents and TVT/ECT at trough levels. aPL positive IgG spiking of PNP had no effect on rivaroxaban's anticoagulant action on thrombin generation or rivaroxaban anti-Xa levels.

CONCLUSIONS

The TVT/ECT ratio and Textarin time were not affected even at peak rivaroxaban levels, enabling detection of LA ex vivo. aPL had no effects on rivaroxaban's anticoagulant action in vitro.

摘要

简介

利伐沙班会影响狼疮抗凝物(LA)检测,抗磷脂抗体(aPL)可能会干扰利伐沙班的抗凝作用。

目的

确定利伐沙班对 LA 检测的影响,以及 aPL 对利伐沙班抗凝作用的影响。

方法

将利伐沙班和 52 种 IgG 制剂(20 种 LA+ve、12 种 LA-ve 血栓性抗磷脂综合征 [APS] 患者和 20 种正常对照 [NC])加入混合正常血浆(PNP)中进行相关研究。还研究了接受利伐沙班 20mg 每日一次的 APS 患者的 LA 检测。

结果

体外向样本中加入利伐沙班,使用 Textarin 时间、Taipan 蛇毒时间/ Ecarin 凝血时间(TVT/ECT)、稀释凝血酶原时间(dPT)和内部稀释 Russell 蝰蛇毒时间(DRVVT),均未出现假阳性 LA,但在大多数 NC 和 LA 阴性 IgG 中,使用两种商业 DRVVT 试剂在 250ng/mL 而非 50ng/mL 利伐沙班时出现假阳性。离体研究:6 名服用利伐沙班的 LA+ve 患者在 TVT/ECT 和 DRVVT 检测中仍为 LA 阳性,利伐沙班峰值(162-278ng/mL)和谷值(30-85ng/mL)水平。6 名 LA-ve 患者在两种 DRVVT 试剂下(检测/确认比值中位数 [置信区间],1.6 [1.3-1.8],1.6 [1.4-1.9])似乎成为 LA+ve,但在利伐沙班峰值时,TVT/ECT 检测结果仍为 LA-ve,在利伐沙班谷值时,两种 DRVVT 试剂和 TVT/ECT 检测结果均为 LA-ve。PNP 中 aPL 阳性 IgG 加标对凝血酶生成或利伐沙班抗 Xa 水平无影响。

结论

即使在利伐沙班峰值水平,TVT/ECT 比值和 Textarin 时间也不受影响,从而能够进行体外 LA 检测。aPL 对利伐沙班的体外抗凝作用无影响。

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