使用Heptest-STAT凝血方法测定患者血浆中的非维生素K拮抗剂口服抗凝剂。

Measurement of Non-Vitamin K Antagonist Oral Anticoagulants in Patient Plasma Using Heptest-STAT Coagulation Method.

作者信息

Du Shanshan, Harenberg Job, Krämer Sandra, Krämer Roland, Wehling Martin, Weiss Christel

机构信息

*Clinical Pharmacology Mannheim, Medical Faculty Mannheim, Ruprecht-Karls University Heidelberg, Mannheim; †Institute of Inorganic Chemistry, Ruprecht-Karls University of Heidelberg, Heidelberg; and ‡Biometry and Statistics, Medical Faculty Mannheim, Ruprecht-Karls University Heidelberg, Mannheim, Germany.

出版信息

Ther Drug Monit. 2015 Jun;37(3):375-80. doi: 10.1097/FTD.0000000000000157.

DOI:10.1097/FTD.0000000000000157

PMID:25525760

Abstract

BACKGROUND

Non-vitamin K antagonist oral anticoagulants (NOACs) are approved for several indications for prophylaxis of thromboembolism at fixed oral doses. The analysis of NOAC activity/concentration may be required in special patient populations. Heptest coagulation assay determines both factor Xa and thrombin inhibitors. The objective of investigations is to analyze the effects of both groups of NOACs on this assay.

METHODS

The performance of a modified Heptest-STAT clotting assay was compared with specific chromogenic substrate assays for factor Xa (Coamatic, HemosIL) and thrombin (direct thrombin inhibitor assay and S2238 chromogenic assays) for the determination of rivaroxaban, apixaban, and dabigatran in plasma from patients on treatment.

RESULTS

For rivaroxaban (n = 74), the concentrations (mean and SD) of Heptest-STAT versus Coamatic and HemosIL assays were 179.3 ± 85.8 ng/mL versus 199.3 ± 105.7 ng/mL and 212.4 ± 115.9 ng/mL (P < 0.0001), and for apixaban (n = 26) 232.8 ± 10.0 ng/mL versus 178.4 ± 64.4 ng/mL (P < 0.0001) and 182.1 ± 73.1 ng/mL (P = 0.0002). For dabigatran (n = 74), the values of Heptest-STAT were 92.3 ± 65.0 ng/mL versus 124.3 ± 85.6 ng/mL (direct thrombin inhibitor assay, P < 0.0001) and 107.5 ± 59.7 ng/mL (S2238 assay, P = 0.0015), respectively. The values of the intraclass coefficient of correlation ranged from 0.64 to 0.91 (Bland-Altman analysis).

CONCLUSIONS

The objective of the study was achieved by demonstrating a high correlation of the Heptest-STAT coagulation assay with chromogenic assays for factor Xa inhibiting NOACs and acceptably good correlation with thrombin inhibiting NOACs in plasma samples of patients on treatment.

摘要

背景

非维生素K拮抗剂口服抗凝药（NOACs）已被批准用于多种固定口服剂量预防血栓栓塞的适应症。特殊患者群体可能需要分析NOAC的活性/浓度。Heptest凝血试验可同时测定Xa因子和凝血酶抑制剂。研究目的是分析这两类NOACs对此试验的影响。

方法

将改良的Heptest-STAT凝血试验的性能与用于测定治疗中患者血浆里利伐沙班、阿哌沙班和达比加群的Xa因子（Coamatic、HemosIL）和凝血酶（直接凝血酶抑制剂试验和S2238显色试验）的特定显色底物试验进行比较。

结果

对于利伐沙班（n = 74），Heptest-STAT试验与Coamatic试验和HemosIL试验的浓度（均值和标准差）分别为179.3±85.8 ng/mL与199.3±105.7 ng/mL和212.4±115.9 ng/mL（P < 0.0001）；对于阿哌沙班（n = 26），分别为232.8±10.0 ng/mL与178.4±64.4 ng/mL（P < 0.0001）和182.1±73.1 ng/mL（P = 0.0002）。对于达比加群（n = 74），Heptest-STAT试验的值分别为92.3±65.0 ng/mL与124.3±85.6 ng/mL（直接凝血酶抑制剂试验，P < 0.0001）和107.5±59.7 ng/mL（S2238试验，P = 0.0015）。组内相关系数值范围为0.64至0.91（Bland-Altman分析）。