Anti Xa oral anticoagulants inhibit in vivo platelet activation by modulating glycoprotein VI shedding

详细信息    查看全文

• 作者：Pasquale Pignatelli ; MD^a ; ¹ ; ^{pasquale.pignatelli@uniroma1.it" class="auth_mail" title="E-mail the corresponding author} ; Daniele Pastori ; MD^a ; ¹ ; Simona Bartimoccia ; PhD^a ; Danilo Menichelli^b ; Tommasa Vicario ; MD^a ; Cristina Nocella ; PhD^a ; Roberto Carnevale ; PhD^a ; ^b ; Francesco Violi ; MD^a
• 关键词：Atrial fibrillation ; Thromboxane ; Warfarin ; Anti Xa non-vitamin k oral anticoagulant ; Platelet inhibitor ; Glycoprotein VI
• 刊名：Pharmacological Research
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：113
• 期：part_PA
• 页码：484-489
• 全文大小：1050 K

文摘

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 10 mg/day (n = 40), or rivaroxaban 20 mg/day (n = 40). Patients were balanced for sex, age and cardiovascular risk factors. Platelet activation by urinary excretion of 11-dehydro-thromboxane (Tx) B₂ and soluble GPVI (sGPVI) were analysed at baseline and after 3 months of treatment. Baseline TxB₂ value was 155.2 ± 42.7 ng/mg creatinine. The 3 months-variation of urinary excretion of TxB₂ 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 TxB₂ (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 TxB₂ 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 TxB₂ excretion compared to warfarin, suggesting that NOACs possess antiplatelet property.