Comparison of clot waveform analysis with or without adjustment between prothrombin time and activated partial thromboplastin time assays to assess in vitro effects of direct oral anticoagulants

IF 3.2 3区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Clinica Chimica Acta Pub Date : 2024-07-24 DOI:10.1016/j.cca.2024.119887
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Abstract

Background

Clot waveform analysis (CWA) reportedly enhances the interpretation of clotting time measurement. This study aimed to compare CWA between prothrombin time (PT) and activated partial thromboplastin time (APTT) assays for better understanding how to apply CWA for assessing effects of direct oral anticoagulants (DOACs).

Methods

Samples were prepared by spiking plasma with rivaroxaban, apixaban, edoxaban, or dabigatran. To compensate the influence of fibrinogen, CWA parameters were adjusted by unifying maximum changes in transmittance in clotting reaction curves detected by the optical system.

Results

Non-adjusted PT-CWA parameters unexpectedly rose at low drug concentrations but declined at high drug concentrations while adjusted PT-CWA parameters exhibited dose-dependent decrease. Both non-adjusted and adjusted APTT-CWA parameters showed dose-dependent decrease. Adjusted CWA parameters were applicable to Hill plot analysis. All DOACs exhibited Hill coefficients indicating positively cooperative effects regarding most adjusted PT-CWA parameters. Regarding adjusted APTT-CWA parameters, rivaroxaban, apixaban, and edoxaban exhibited Hill coefficients indicating no or negatively cooperative effects. The observed differences between PT-CWA and APTT-CWA suggested the implication of thrombin positive feedback in DOAC effects.

Conclusion

The results revealed distinct features of DOAC effects in extrinsic and intrinsic pathways. To ascertain the clinical implication, further studies using clinical samples are needed.

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比较凝血酶原时间和活化部分凝血活酶时间测定法之间有无调整的凝块波形分析,以评估直接口服抗凝剂的体外效应。
背景:据报道,凝血波形分析(CWA)可增强对凝血时间测量的解释。本研究旨在比较凝血酶原时间(PT)和活化部分凝血活酶时间(APTT)测定法之间的凝血波形分析,以更好地了解如何应用凝血波形分析评估直接口服抗凝剂(DOACs)的效果:通过在血浆中添加利伐沙班、阿哌沙班、埃多沙班或达比加群制备样本。为了补偿纤维蛋白原的影响,通过统一光学系统检测到的凝血反应曲线中透射率的最大变化来调整 CWA 参数:结果:未调整的 PT-CWA 参数在药物浓度低时意外上升,但在药物浓度高时下降,而调整后的 PT-CWA 参数呈现剂量依赖性下降。未调整和调整后的 APTT-CWA 参数均呈剂量依赖性下降。调整后的 CWA 参数适用于希尔图分析。所有 DOACs 都显示出希尔系数,表明在大多数调整后的 PT-CWA 参数方面存在正合作效应。在调整后的 APTT-CWA 参数方面,利伐沙班、阿哌沙班和埃多沙班的希尔系数显示无协同效应或协同效应为负。观察到的 PT-CWA 和 APTT-CWA 之间的差异表明,凝血酶正反馈对 DOAC 的作用有影响:结论:研究结果揭示了DOAC效应在外因和内因途径中的不同特征。要确定其临床意义,还需要使用临床样本进行进一步研究。
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来源期刊
Clinica Chimica Acta
Clinica Chimica Acta 医学-医学实验技术
CiteScore
10.10
自引率
2.00%
发文量
1268
审稿时长
23 days
期刊介绍: The Official Journal of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Clinica Chimica Acta is a high-quality journal which publishes original Research Communications in the field of clinical chemistry and laboratory medicine, defined as the diagnostic application of chemistry, biochemistry, immunochemistry, biochemical aspects of hematology, toxicology, and molecular biology to the study of human disease in body fluids and cells. The objective of the journal is to publish novel information leading to a better understanding of biological mechanisms of human diseases, their prevention, diagnosis, and patient management. Reports of an applied clinical character are also welcome. Papers concerned with normal metabolic processes or with constituents of normal cells or body fluids, such as reports of experimental or clinical studies in animals, are only considered when they are clearly and directly relevant to human disease. Evaluation of commercial products have a low priority for publication, unless they are novel or represent a technological breakthrough. Studies dealing with effects of drugs and natural products and studies dealing with the redox status in various diseases are not within the journal''s scope. Development and evaluation of novel analytical methodologies where applicable to diagnostic clinical chemistry and laboratory medicine, including point-of-care testing, and topics on laboratory management and informatics will also be considered. Studies focused on emerging diagnostic technologies and (big) data analysis procedures including digitalization, mobile Health, and artificial Intelligence applied to Laboratory Medicine are also of interest.
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