改良血栓弹力图检测全血中利伐沙班和阿哌沙班抗凝活性：一项诊断检测研究。

Modified ROTEM for the detection of rivaroxaban and apixaban anticoagulant activity in whole blood: A diagnostic test study.

机构信息

From the INSERM UMR_S1140, Faculté de Pharmacie (CP, GJ, VS, IG, SG, PG, BL, CMS), Université Paris Descartes (CP, GJ, VS, IG, SG, EC, PG, BL, CMS), Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Cochin (CP, GJ, CMS), AP-HP, Hôpital Lariboisière, Paris (VS, AS), CHU Pontchaillou, Rennes (IG), AP-HP, Hôpital Européen Georges Pompidou (SG, PG), EA3518, Hôpital Saint Louis (AS), INSERM UMR_S1144, Faculté de Pharmacie (EC), Laboratoire de Biomathématiques, Faculté de Pharmacie, Université Paris Descartes (EC) and Université Pierre et Marie Curie, Paris, France (JG).

出版信息

Eur J Anaesthesiol. 2019 Jun;36(6):449-456. doi: 10.1097/EJA.0000000000000903.

DOI:10.1097/EJA.0000000000000903

PMID:30308522

Abstract

BACKGROUND

Rapid detection of the anticoagulant effect of oral factor Xa (FXa) inhibitors may be essential in several emergency clinical situations. Specific assays quantifying the drugs are performed in plasma and require a turnaround time that is too long to be useful in emergency situations. Rotational thromboelastometry (ROTEM) is a whole blood coagulation assay of blood viscoelasticity and could be of interest for FXa inhibitor detection in emergency. However, conventional ROTEM reagents only detect high amounts of inhibitors.

OBJECTIVE

The aim of this study was first to assess the effect of whole blood components on the viscoelastic measurement of the effects of FXa inhibitors, and second to evaluate whether a modified ROTEM, triggered with a low amount of tissue factor and a saturating amount of phospholipid vesicles, can reliably detect low levels of FXa inhibitor activity in whole blood.

DESIGN

Diagnostic test study.

SETTINGS

A university research laboratory. From November 2014 to April 2016.

PATIENTS

Sixty-six patients: 30 treated with rivaroxaban, 17 with apixaban and 19 without treatment.

INTERVENTION

ROTEM was triggered with 2.5 pmol l of tissue factor and 10 μmol l of phospholipid vesicles.

MAIN OUTCOME MEASURES

Modified ROTEM parameters were measured in different experimental conditions: platelet-poor plasma (PPP), platelet-rich plasma, PPP supplemented with fibrinogen and reconstituted whole blood with various haematocrit levels adjusted between 30 and 60%. Modified ROTEM was further validated using whole blood from patients who were either treated or not treated with FXa inhibitors.

RESULTS

Modified ROTEM allowed detection of as little as 25 ng ml FXa inhibitors in PPP, with at least a 1.4-fold increase of the clotting time (P ≤ 0.02). Neither changes of fibrinogen concentration nor variations of platelet count or haematocrit precluded FXa inhibitor detection. A lengthened modified ROTEM clotting time of more than 197 s allowed detection of FXa inhibitor concentrations above 30 ng ml in whole blood with 90% sensitivity and 85% specificity.

CONCLUSION

Modified ROTEM may be applicable in emergency situations for the detection of FXa inhibitors in whole blood.

摘要

背景

快速检测口服因子 Xa（FXa）抑制剂的抗凝效果在几种急诊临床情况下可能至关重要。用于定量检测药物的特定检测方法在血浆中进行，所需的周转时间过长，无法在急诊情况下使用。旋转血栓弹性测定（ROTEM）是一种全血凝血检测血液粘弹性的方法，可能对急诊 FXa 抑制剂检测有意义。然而，常规 ROTEM 试剂仅能检测到大量抑制剂。

目的

本研究的目的首先是评估全血成分对 FXa 抑制剂效应的粘弹性测量的影响，其次是评估是否可以通过使用低量组织因子和饱和量磷脂囊泡触发的改良 ROTEM 可靠地检测全血中低水平的 FXa 抑制剂活性。

设计

诊断测试研究。

设置

大学研究实验室。2014 年 11 月至 2016 年 4 月。

患者

66 例患者：30 例接受利伐沙班治疗，17 例接受阿哌沙班治疗，19 例未治疗。

干预

ROTEM 用 2.5pmol l 的组织因子和 10μmol l 的磷脂囊泡触发。

主要观察指标

在不同的实验条件下测量改良 ROTEM 参数：血小板缺乏的血浆（PPP）、富含血小板的血浆、PPP 补充纤维蛋白原和各种血细胞比容水平在 30%至 60%之间调整的再构成全血。使用接受或未接受 FXa 抑制剂治疗的患者的全血进一步验证改良 ROTEM。

结果

改良 ROTEM 可在 PPP 中检测到低至 25ng/ml 的 FXa 抑制剂，凝血时间至少延长 1.4 倍（P≤0.02）。纤维蛋白原浓度的变化、血小板计数或血细胞比容的变化都不排除 FXa 抑制剂的检测。改良 ROTEM 凝血时间延长超过 197 s 可检测到全血中 FXa 抑制剂浓度高于 30ng/ml，敏感性为 90%，特异性为 85%。