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1型糖尿病患者的总维生素K水平较低,且对直接抗凝剂的敏感性增加。

Type 1 diabetes mellitus patients had lower total vitamin K levels and increased sensitivity to direct anticoagulants.

作者信息

Carazo Alejandro, Paclíková Markéta, Fadraersada Jaka, Alva-Gallegos Raúl, Skořepa Pavel, Gunaseelan Catherine, Matoušová Kateřina, Mrštná Kristýna, Krčmová Lenka Kujovská, Šmahelová Alena, Blaha Vladimír, Mladěnka Přemysl

机构信息

Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Hradec Králové, Czech Republic.

3rd Department of Internal Medicine-Metabolic Care and Gerontology, University Hospital and Faculty of Medicine in Hradec Králové, Charles University, Hradec Králové, Czech Republic.

出版信息

PLoS One. 2025 Jun 23;20(6):e0326580. doi: 10.1371/journal.pone.0326580. eCollection 2025.

Abstract

The abnormalities in blood coagulation in patients with diabetes can lead to a prothrombotic state and requirement for the administration of direct anticoagulants. However, no comparative studies have been conducted on the effects of different direct anticoagulants. A head-to-head investigation of the impact of anticoagulants in 50 patients of type 1 diabetes mellitus (DMT1) was performed, and the data were compared to 50 generally healthy individuals. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were measured in plasma treated with vehicle, heparin, or four direct anticoagulants at 1 μM. In addition to common biochemical parameters, novel inflammatory markers (neopterin, kynurenine/tryptophan ratio) and major vitamin K forms were measured. Heparin and dabigatran treatments resulted in prolonged coagulation in DMT1 patients compared to healthy individuals in both tests (both p < 0.001). The same phenomenon was observed for rivaroxaban and apixaban-treated samples in PT (p < 0.001). Interestingly, healthy volunteers had higher total vitamin K levels than DMT1. Further analysis suggested that observed coagulation differences were not caused by differences in glycemia but were rather associated with an unexpected, better lipid profile of our DMT1 group. There were also correlations between prolongation of coagulation brought about by the most active anticoagulants and inflammatory markers, and hence inflammatory state probably also contributed to the differences, as well as the mentioned differences in vitamin K levels. Conclusively, this paper suggests the suitability for controlling the effects of direct anticoagulants in DMT1 patients.

摘要

糖尿病患者的血液凝固异常可导致血栓前状态,并需要使用直接抗凝剂。然而,尚未对不同直接抗凝剂的效果进行比较研究。我们对50例1型糖尿病(DMT1)患者进行了抗凝剂影响的直接对比研究,并将数据与50名一般健康个体进行了比较。在使用赋形剂、肝素或四种1μM直接抗凝剂处理的血浆中测量凝血酶原时间(PT)和活化部分凝血活酶时间(aPTT)。除了常见的生化参数外,还测量了新型炎症标志物(新蝶呤、犬尿氨酸/色氨酸比值)和主要维生素K形式。在两项测试中,与健康个体相比,肝素和达比加群治疗均导致DMT1患者的凝血时间延长(均p < 0.001)。在PT测试中,利伐沙班和阿哌沙班处理的样本也观察到相同现象(p < 0.001)。有趣的是,健康志愿者的总维生素K水平高于DMT1患者。进一步分析表明,观察到的凝血差异不是由血糖差异引起的,而是与我们DMT1组意外更好的血脂谱有关。最活跃的抗凝剂引起的凝血延长与炎症标志物之间也存在相关性,因此炎症状态可能也导致了这些差异,以及上述维生素K水平的差异。总之,本文表明了控制直接抗凝剂对DMT1患者效果的适用性。

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