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α干扰素治疗可增加骨髓增殖性肿瘤患者的促血栓形成生物标志物。

Interferon Alpha Therapy Increases Pro-Thrombotic Biomarkers in Patients with Myeloproliferative Neoplasms.

作者信息

Faille Dorothée, Lamrani Lamia, Loyau Stéphane, Huisse Marie-Geneviève, Bourrienne Marie-Charlotte, Alkhaier Sawsaneh, Cassinat Bruno, Boulaftali Yacine, Debus Jérôme, Jandrot-Perrus Martine, Chomienne Christine, Dosquet Christine, Ajzenberg Nadine

机构信息

Université de Paris, INSERM UMR_S1148, F-75877 Paris CEDEX 18, France.

Laboratoire d'Hématologie, AP-HP, Hôpital Bichat, F-75877 Paris CEDEX 18, France.

出版信息

Cancers (Basel). 2020 Apr 17;12(4):992. doi: 10.3390/cancers12040992.

Abstract

Myeloproliferative neoplasms (MPN) are associated with an increased risk of arterial and venous thrombosis. Pegylated-interferon alpha (IFN) and hydroxyurea (HU) are commonly used to treat MPN, but their effect on hemostasis has not yet been studied. The aim of our study was to determine whether IFN and HU impact the biological hemostatic profile of MPN patients by studying markers of endothelial, platelet, and coagulation activation. A total of 85 patients (50 polycythemia vera and 35 essential thrombocythemia) were included: 28 treated with IFN, 35 with HU, and 22 with no cytoreductive drug (non-treated, NT). Von Willebrand factor, shear-induced platelet aggregation, factor VIII coagulant activity (FVIII:C), fibrinogen, and thrombin generation with and without exogenous thrombomodulin were significantly higher in IFN-treated patients compared to NT patients, while protein S anticoagulant activity was lower. In 10 patients in whom IFN therapy was discontinued, these hemostatic biomarkers returned to the values observed in NT patients, strongly suggesting an impact of IFN therapy on endothelial and coagulation activation. Overall, our study shows that treatment with IFN is associated with significant and reversible effects on the biological hemostatic profile of MPN patients. Whether they could be associated with an increased thrombotic risk remains to be determined in further randomized clinical studies.

摘要

骨髓增殖性肿瘤(MPN)与动脉和静脉血栓形成风险增加相关。聚乙二醇化干扰素α(IFN)和羟基脲(HU)常用于治疗MPN,但它们对止血的影响尚未得到研究。我们研究的目的是通过研究内皮、血小板和凝血激活标志物来确定IFN和HU是否会影响MPN患者的生物学止血特征。共纳入85例患者(50例真性红细胞增多症和35例原发性血小板增多症):28例接受IFN治疗,35例接受HU治疗,22例未使用细胞减灭药物(未治疗,NT)。与NT患者相比,接受IFN治疗的患者血管性血友病因子、剪切诱导的血小板聚集、凝血因子VIII促凝活性(FVIII:C)、纤维蛋白原以及有无外源性血栓调节蛋白时的凝血酶生成均显著升高,而蛋白S抗凝活性降低。在10例停止IFN治疗的患者中,这些止血生物标志物恢复到NT患者中观察到的值,强烈提示IFN治疗对内皮和凝血激活有影响。总体而言,我们的研究表明,IFN治疗对MPN患者的生物学止血特征有显著且可逆的影响。它们是否与血栓形成风险增加相关仍有待进一步的随机临床研究确定。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/968a/7226618/2f29999648c7/cancers-12-00992-g001.jpg

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