Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States.
Department of Laboratory Medicine and Pathology, Seattle Children's Hospital, Seattle, WA, United States.
J Appl Lab Med. 2024 Mar 1;9(2):305-315. doi: 10.1093/jalm/jfad081.
Direct oral anticoagulants (DOACs) and fondaparinux with stable pharmacokinetics are commonly used anticoagulants for outpatient care. Due to the lack of monitoring requirements, drug-specific assays are not available in most hospital laboratories, but drug levels are needed in some urgent/emergency situations. This study describes the development of a qualitative screen for the presence of DOAC or fondaparinux using coagulation tests found in most laboratories.
The DOAC screen is composed of a heparin anti-Xa activity assay and thrombin time (TT) assay. The STA®-Liquid-Anti-Xa assay calibrated with Stago Multi Hep® and STA®-TT were run on STA-R Max® analyzers. The anti-Xa activity and TT assays were repeated 5 times in samples of commercially available calibrators and controls for each drug: fondaparinux, dabigatran, rivaroxaban, apixaban, and edoxaban. Statistical analysis and correlations were performed for anti-Xa activity and TT results for each drug and pooled normal plasma.
A significant correlation was found between heparin-calibrated anti-Xa levels and fondaparinux, rivaroxaban, apixiban, and edoxaban (r2 = 0.99-1.0). Dabigatran showed a strong linear correlation (r2 = 0.99) with TT. Anti-Xa levels >0.3 IU/mL and TT >25 seconds were determined as cutoffs at our lab for the detection of clinically relevant drug levels of factor Xa inhibitor and direct thrombin inhibitor, respectively.
Our study demonstrates that commonly available heparin anti-Xa activity and TT assays can be used to qualitatively detect DOACs and fondaparinux and provides a method to establish a qualitative interpretation.
具有稳定药代动力学的直接口服抗凝剂（DOAC）和磺达肝素通常用于门诊抗凝治疗。由于缺乏监测要求，大多数医院实验室都没有特定药物的检测方法，但在某些紧急情况下需要检测药物水平。本研究描述了一种使用大多数实验室都具备的凝血检测方法定性筛查 DOAC 或磺达肝素的方法。
DOAC 筛查由肝素抗 Xa 活性测定和凝血酶时间（TT）测定组成。使用 Stago Multi Hep®校准的 STA®-Liquid-Anti-Xa 测定和 STA®-TT 测定在 STA-R Max®分析仪上运行。在每种药物的市售校准品和对照品样本中重复进行 5 次抗 Xa 活性和 TT 测定：磺达肝素、达比加群、利伐沙班、阿哌沙班和依度沙班。对每种药物和混合正常血浆的抗 Xa 活性和 TT 结果进行了统计分析和相关性分析。
肝素校准的抗 Xa 水平与磺达肝素、利伐沙班、阿哌沙班和依度沙班呈显著相关（r2=0.99-1.0）。TT 与达比加群呈强线性相关（r2=0.99）。我们实验室将抗 Xa 水平>0.3 IU/mL 和 TT>25 秒分别确定为检测临床相关因子 Xa 抑制剂和直接凝血酶抑制剂药物水平的临界值。
本研究表明，常用的肝素抗 Xa 活性和 TT 测定可用于定性检测 DOAC 和磺达肝素，并提供了一种建立定性解释的方法。
