Pignatelli Pasquale, Pastori Daniele, Bartimoccia Simona, Menichelli Danilo, Vicario Tommasa, Nocella Cristina, Carnevale Roberto, Violi Francesco
IClinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
IClinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
Pharmacol Res. 2016 Nov;113(Pt A):484-489. doi: 10.1016/j.phrs.2016.09.035. Epub 2016 Sep 28.
Anti Xa non-vitamin K oral anticoagulants (anti Xa NOACs) seem to possess antiplatelet effect in vitro, but it is unclear if this occurs also in vivo. Aim of the study was to compare the effect on platelet activation of two anti Xa NOACs, namely apixaban and rivaroxaban, to warfarin, and to investigate the potential underlying mechanism by evaluating soluble glycoprotein GPVI (sGPVI), a protein involved in platelet activation. We performed a cross-sectional including AF patients treated with warfarin (n=30), or apixaban 10mg/day (n=40), or rivaroxaban 20mg/day (n=40). Patients were balanced for sex, age and cardiovascular risk factors. Platelet activation by urinary excretion of 11-dehydro-thromboxane (Tx) B and soluble GPVI (sGPVI) were analysed at baseline and after 3 months of treatment. Baseline TxB value was 155.2±42.7ng/mg creatinine. The 3 months-variation of urinary excretion of TxB was -6.5% with warfarin (p=0.197), -29% with apixaban (p<0.001) and -31% with rivaroxaban (p<0.001). Use of anti Xa NOACs was independently associated to the variation of urinary TxB (B: -0.469, p<0.001), after adjustment for clinical characteristics; sGPVI was significantly lower in patients treated with NOACs at 3 months (p<0.001), while only a trend for the warfarin group (p=0.116) was observed. The variation of sGPVI was correlated with that of TxB in the NOACs group (Rs: 0.527, p<0.001). In 15 patients (5 per each group) platelet recruitment was significantly lowered at 3 months by NOACs (p<0.001), but not by warfarin. The study provides evidence that anti Xa NOACs significantly inhibit urinary TxB excretion compared to warfarin, suggesting that NOACs possess antiplatelet property.
抗Xa非维生素K口服抗凝剂（抗Xa NOACs）在体外似乎具有抗血小板作用，但尚不清楚在体内是否也会发生这种情况。本研究的目的是比较两种抗Xa NOACs（阿哌沙班和利伐沙班）与华法林对血小板活化的影响，并通过评估可溶性糖蛋白GPVI（sGPVI，一种参与血小板活化的蛋白质）来研究潜在的机制。我们进行了一项横断面研究，纳入了接受华法林治疗的房颤患者（n = 30）、或阿哌沙班10mg/天治疗的患者（n = 40）、或利伐沙班20mg/天治疗的患者（n = 40）。患者在性别、年龄和心血管危险因素方面保持均衡。在基线和治疗3个月后分析尿中11-脱氢血栓烷（Tx）B的排泄和可溶性GPVI（sGPVI）以评估血小板活化情况。基线TxB值为155.2±42.7ng/mg肌酐。华法林治疗后尿中TxB排泄的3个月变化为-6.5%（p = 0.197），阿哌沙班治疗后为-29%（p<0.001），利伐沙班治疗后为-31%（p<0.001）。在调整临床特征后，使用抗Xa NOACs与尿中TxB的变化独立相关（B：-0.469，p<0.001）；在3个月时，接受NOACs治疗的患者sGPVI显著降低（p<0.001），而华法林组仅观察到一种趋势（p = 0.116）。在NOACs组中，sGPVI的变化与TxB的变化相关（Rs：0.527，p<0.001）。在15名患者（每组5名）中，3个月时NOACs显著降低了血小板募集（p<0.001），但华法林未降低。该研究提供了证据，表明与华法林相比，抗Xa NOACs显著抑制尿中TxB排泄，提示NOACs具有抗血小板特性。
