探討急性缺血性中風病人直接型口服抗凝血劑濃度與凝血功能檢測的關聯性

The correlation between direct oral anticoagulant concentration and coagulation tests among acute ischemic stroke patients

背景：在服用直接型抗凝血劑（direct oral anticoagulants，DOACs）的病人，又發生急性缺血性中風，此時血中藥物的濃度是臨床處置的重要依據，但DOACs的濃度測試臨床不普及。本研究目的在探討服用DOACs藥物期間因急性缺血性中風到院病人，以到院時的凝血酶原時間（prothrombin time，PT），來預估FXa抑制劑的藥物活性、與部份凝血活酶時間（activated partial thromboplastin time，aPTT），來預測dabigatran的藥物活性的能力。
方法：本研究收案DOACs治療期間發生缺血性中風的病人，收集其到院時的血液，透過高解析液相層析串聯質譜儀檢測DOACs濃度，同時收集PT、aPTT檢驗結果。DOACs濃度區分為（1）低藥理作用（<50 ng/mL）或（2）高藥理作用（≥50 ng/mL），而PT<11.5秒與aPTT<32.5秒則定義為凝血功能正常。
結果：於2020年三月至2023年十二月間，本研究共收案94位病人，含72位FXa抑制劑使用者與22位dabigatran使用者。FXa抑制劑組中，有65位病人檢測PT，其中共36位病人（45.4%）PT表現與藥物濃度相符，含17位病人（26.2%）PT延長且DOACs高藥理作用與19位病人（29.2%）PT正常且DOACs低藥理作用。Dabigatran組中，有18位病人檢測aPTT，共15位病人（83.3%）aPTT表現與藥物濃度相符，含9位病人（50.0%）aPTT延長且DOACs高藥理作用與6位病人（33.3%）aPTT正常且DOACs低藥理作用。
結論：本研究發現服用DOACs藥物期間仍發生缺血性中風的病人，PT有近五成與FXa抑制劑的藥理作用相符，而aPTT則有近八成與dabigatran藥理作用相符，但受限於本研究族群小，若要使用PT或aPTT來評估DOACs藥理作用之臨床實用性尚待進一步研究。

Background: Among patients who suffered from ischemic stroke (IS) during direct oral anticoagulants (DOACs) therapy, understanding the emergent DOACs levels is crucial for making critical decisions. However, rapid DOACs concentration tests are not widely available. The purpose of this investigation is to analyze the correlation between prothrombin time (PT) and factor Xa (FXa) inhibitor concentrations and the correlation between activated partial thromboplastin time (aPTT) and dabigatran concentrations.
Methods: Patients who suffered from IS during DOACs therapy were enrolled to collect blood sampling upon hospital presentation. The DOACs concentrations were measured by using the Ultra-performance liquid chromatography–mass spectrometry. Additionally, PT and aPTT were tested. DOACs concentration < 50 ng/mL is defined as low pharmacological effect and≥50 ng/mL is defined as high pharmacological effect. PT<11.5 seconds and aPTT<32.5 seconds were defined as normal.
Results: During the study period, a total of 94 patients were enrolled, consisting of 72 FXa inhibitor users and 22 dabigatran users. In the FXa inhibitors group, 65 patients had PT values. Among them, 36 patients (45.4%) exhibited concordant PT-FXa inhibitor pharmacological activity, including 17 patients with prolonged PT and high FXa inhibitor pharmacological effects, and 19 patients with normal PT and low FXa inhibitor pharmacological effects. In the dabigatran group, 18 patients had aPTT values. Among them, 15 patients (83.3%) demonstrated concordant aPTT and dabigatran pharmacological activity, including 9 patients with prolonged aPTT and high dabigatran pharmacological effects, and 6 patients with normal aPTT and low dabigatran pharmacological effects.
Conclusion: Among DOACs users who suffered from IS, approximately half of FXa inhibitor users exhibit concordant PT values and DOACs pharmacological effects, while approximately 80% of dabigatran users demonstrate concordant aPTT values and DOACs pharmacological effects. However, due to the small sample size, the clinical usefulness of PT or aPTT in evaluating DOACs pharmacological activity remains unclear.