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阿加曲班在高、低凝血活性样本中对多种活化部分凝血活酶时间(APTT)试剂作用的变异性

Variability of Argatroban Effects on the Multiple APTT Reagents in High and Low Coagulation Activity Samples.

作者信息

Kumano Osamu, Ieko Masahiro, Hashiguchi Teruto, Ito Takashi, Yamazaki Satoshi, Naito Sumiyoshi, Yamazaki Masako

机构信息

Health and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Takamatsu, Japan.

Department of Nursing, Sapporo University of Health Sciences, Sapporo, Hokkaido, Japan.

出版信息

Int J Lab Hematol. 2025 Oct;47(5):923-930. doi: 10.1111/ijlh.14488. Epub 2025 Apr 23.

Abstract

INTRODUCTION

Argatroban is routinely monitored using activated partial thromboplastin time (APTT), with a recommended target range of 1.5-3.0 times. Although this range was established based on clinical trial data, including several APTT reagents, the differences in reactivity among APTT reagents remain unclear. This study compared the reactivity of six commercial APTT reagents to argatroban in normal and abnormal plasma samples.

MATERIALS AND METHODS

Normal samples were spiked with argatroban and five abnormal samples: low coagulation factor activity, high factor VIII, high factor VIIa, low fibrinogen, and high fibrinogen. Drug concentrations were adjusted to 0, 0.5, 1.0, 1.5, and 2.0 μg/mL in each plasma. Six APTT reagents, including silica or ellagic acid activator and phospholipids derived from synthetic or natural sources, were tested.

RESULTS

The APTT ratio range among the six reagents was 2.4-3.2 in normal plasma at a concentration of 2.0 μg/mL. The sample showing the most expanded range was low coagulation activity (3.3-5.2), and the range in the sample with high factor VIII activity decreased (1.5-2.2).

CONCLUSIONS

A reactivity difference was observed in argatroban-spiked samples, which increased in abnormal plasma samples. APTT may not reflect the anticoagulant activity of argatroban in patients with abnormal coagulation activity. The reactivity of APTT should be confirmed in each laboratory, and patient background coagulation status should be assessed before monitoring is conducted using the APTT ratio.

摘要

引言

阿加曲班通常采用活化部分凝血活酶时间(APTT)进行监测,推荐的目标范围是1.5至3.0倍。尽管该范围是根据临床试验数据确定的,包括几种APTT试剂,但APTT试剂之间反应性的差异仍不清楚。本研究比较了六种市售APTT试剂在正常和异常血浆样本中对阿加曲班的反应性。

材料与方法

将阿加曲班添加到正常样本和五个异常样本中:低凝血因子活性、高因子VIII、高因子VIIa、低纤维蛋白原和高纤维蛋白原。在每个血浆中,将药物浓度调整为0、0.5、1.0、1.5和2.0μg/mL。测试了六种APTT试剂,包括二氧化硅或鞣花酸激活剂以及源自合成或天然来源的磷脂。

结果

在浓度为2.0μg/mL的正常血浆中,六种试剂的APTT比值范围为2.4至3.2。范围扩展最大的样本是低凝血活性样本(3.3至5.2),而高因子VIII活性样本的范围缩小(1.5至2.2)。

结论

在添加阿加曲班的样本中观察到反应性差异,在异常血浆样本中这种差异增大。APTT可能无法反映凝血活性异常患者中阿加曲班的抗凝活性。每个实验室都应确认APTT的反应性,并且在使用APTT比值进行监测之前,应评估患者的背景凝血状态。

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