Department of Hematology and Blood Transfusion, National Centre of Hemostasis and Thrombosis, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic.
Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic ; and.
J Cardiovasc Pharmacol. 2021 Jul 1;78(1):e122-e127. doi: 10.1097/FJC.0000000000001038.
Patients with atrial fibrillation (AF) on long-term direct oral anticoagulants (DOACs) may be at higher risk of bleeding because of higher anti-Xa or anti-IIa levels. However, there is no postmarketing study investigating these DOAC plasma levels at the time of bleeding. The aim of this study was to evaluate DOAC levels at the time of a bleeding emergency. We analyzed 5440 patients examined at our Emergency Department in from April 1, 2019, to September 30, 2019. During this period, we prospective identified 105 consecutive patients with bleeding while on long-term antithrombotic therapy; 49 patients had AF on DOACs. We compared DOAC levels in patients who bled against a control sample of 55 patients who tolerated long-term high dose DOAC therapy without any emergency. Samples of these patients were tested with drug-specific anti-Xa chromogenic analysis (rivaroxaban and apixaban) and with Hemoclot Thrombin Inhibitor assay (dabigatran). Dabigatran-treated patients who bled had significantly higher anti-IIa levels when compared with trough (261.4 ± 163.7 vs. 85.4 ± 57.2 ng/mL, P < 0.001) and peak samples of controls (261.4 ± 163.7 vs. 138.8 ± 78.7 ng/mL, P < 0.05). Similarly, there were significantly higher anti-Xa levels in rivaroxaban-treated and apixaban-treated patients with bleeding compared with trough control samples (rivaroxaban: 245.9 ± 150.2 vs. 52.5 ± 36.4 ng/mL, P <0.001 and apixaban: 311.8 ± 142.5 vs. 119.9 ± 81.7 ng/mL, P < 0.001), as well as in apixaban-treated patients when compared with peak control samples (311.8 ± 142.5 vs. 210.9 ± 88.7 ng/mL, P < 0.05). Finally, rivaroxaban anti-Xa levels in patients who bled tended to be higher compared with peak control samples (245.9 ± 150.2 vs. 177.6 ± 38.6 ng/mL, P = 0.13). This observational study showed a significant difference in anti-IIa and anti-Xa plasma levels in patients with AF with bleeding complications compared with those who tolerated long-term high-dose DOAC therapy without bleeding complications.
患者服用长期直接口服抗凝剂（DOAC）可能会因更高的抗-Xa 或抗-IIa 水平而增加出血风险。然而，目前尚无上市后研究调查这些 DOAC 血浆水平在出血时的情况。本研究旨在评估出血急症时 DOAC 水平。我们分析了 2019 年 4 月 1 日至 9 月 30 日在我们急诊部检查的 5440 名患者。在此期间，我们前瞻性地确定了 105 名连续服用长期抗血栓治疗后出血的患者；49 名患者服用 DOAC 时患有房颤。我们比较了出血患者与 55 名耐受长期高剂量 DOAC 治疗且无紧急情况的对照样本的 DOAC 水平。这些患者的样本使用药物特异性抗-Xa 显色分析（利伐沙班和阿哌沙班）和 Hemoclot 凝血酶抑制剂测定法（达比加群）进行检测。与谷值（261.4±163.7 比 85.4±57.2ng/ml，P<0.001）和对照样本的峰值相比，接受达比加群治疗且出血的患者的抗-IIa 水平显著升高（261.4±163.7 比 138.8±78.7ng/ml，P<0.05）。同样，与谷值对照样本相比，接受利伐沙班和阿哌沙班治疗且出血的患者的抗-Xa 水平显著升高（利伐沙班：245.9±150.2 比 52.5±36.4ng/ml，P<0.001；阿哌沙班：311.8±142.5 比 119.9±81.7ng/ml，P<0.001），与峰值对照样本相比，阿哌沙班治疗的患者也升高（311.8±142.5 比 210.9±88.7ng/ml，P<0.05）。最后，与峰值对照样本相比，出血患者的利伐沙班抗-Xa 水平趋于升高（245.9±150.2 比 177.6±38.6ng/ml，P=0.13）。这项观察性研究表明，与长期耐受高剂量 DOAC 治疗而无出血并发症的患者相比，出血并发症的房颤患者的抗-IIa 和抗-Xa 血浆水平存在显著差异。
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