背景:据报道,凝块波形分析(CWA)增强了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)测定之间的CWA,以更好地了解如何应用CWA评估直接口服抗凝剂(DOAC)的效果。
方法:用利伐沙班加标血浆制备样品,阿哌沙班,edoxaban,或者Dabigatran.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参数在低药物浓度时意外上升,但在高药物浓度时下降,而调整的PT-CWA参数表现出剂量依赖性下降。未调整和调整的APTT-CWA参数均显示剂量依赖性降低。调整后的CWA参数适用于Hill图分析。所有DOAC均表现出希尔系数,表明对大多数调整后的PT-CWA参数具有积极的协同作用。关于调整后的APTT-CWA参数,利伐沙班,阿哌沙班,edoxaban表现出希尔系数,表明没有或负面的合作效应。PT-CWA和APTT-CWA之间观察到的差异表明凝血酶正反馈在DOAC效应中的意义。
结论:结果揭示了外在和内在途径中DOAC效应的明显特征。为了确定临床意义,需要使用临床样本进行进一步研究.
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.
CONCLUSIONS: 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.