- 期刊
直接型抗凝血劑藥物濃度檢測的臨床應用
The Clinical Use of Direct Oral Anticoagulant Concentration Measurement
摘要
直接型抗凝血劑（direct oral anticoagulants, DOACs）療劑範圍，不需定期檢測濃度以評估藥物療效並隨之調整劑量，是心房纖維顫動（atrial fibrillation, AF）病人預防中風與全身性栓塞的第一線藥物。然而，DOACs的代謝與排除路徑，牽涉肝臟酵素cytochrome P（CYP）系統、運送蛋白P-glycoprotein（P-gp），並有一定比例經由腎臟排除，在高齡、腎功能不全、並用具有交互作用的藥物的病人藥物濃度可能改變。藥物濃度的高低與臨床事件有關，過高的藥物濃度可能導致出血，過低的藥物濃度則可能導致中風與栓塞，因此，在特定病人檢測DOACs濃度可協助進行治療的調整。在DOACs治療期間仍發生栓塞或出血事件的病人，檢測事件當下的DOACs濃度，能夠輔助臨床治療的選擇，如給予缺血性中風病人血栓溶解劑治療，或給予出血性中風病人反轉劑治療等。除此之外，急性DOACs濃度也可用以預測中風預後。目前，DOACs檢測臨床不普及，且缺乏明確的療劑範圍。未來仍需大型且長期追蹤的研究，透過穩定治療濃度的收集，搭配急性事件時藥物濃度的檢測，以找出DOACs療劑範圍，甚至更進一步探討濃度正常仍發生栓塞或出血事件的因子。
並列摘要
Direct oral anticoagulants (DOACs) are the first-line therapy for preventing stroke or systemic thromboembolism in atrial fibrillation (AF) patients, because DOACs display wide therapeutic range, do not require routine laboratory monitoring, and the dosing regimen is standardized. However, the metabolism and elimination of DOACs involve the cytochrome P (CYP) system and P-glycoprotein, and they are partially excreted through the kidneys. In elderly patients and those with renal impairment or using medications interacting with DOACs, DOAC exposure can vary. It is well-established that DOAC concentration is associated with clinical outcomes, with high concentrations linked to increased major bleeding and low concentrations associated with stroke or systemic thromboembolism. Monitoring DOAC concentrations in specific populations can help guide therapy adjustments. In patients experiencing thrombosis or bleeding events during DOAC therapy, measuring emergent DOAC concentrations is crucial for determining appropriate clinical management, such as administering thrombolytic therapy for ischemic stroke or reversal agents for major bleeding. Additionally, emergent DOAC concentrations are associated with stroke outcomes. However, barriers to DOAC concentration testing include limited availability and a lack of definitive therapeutic ranges. Large-scale investigations with long-term follow-up are needed to establish therapeutic ranges for DOACs and identify factors associated with thrombosis or bleeding events during DOAC therapy.