Institute for Molecular Cardiovascular Research, University Hospital Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany.
Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
Clin J Am Soc Nephrol. 2022 Jan;17(1):155-170. doi: 10.2215/CJN.04100321. Epub 2021 Nov 8.
Patients with CKD display a significantly higher risk of cardiovascular and thromboembolic complications, with around half of patients with advanced CKD ultimately dying of cardiovascular disease. Paradoxically, these patients also have a higher risk of hemorrhages, greatly complicating patient therapy. Platelets are central to hemostasis, and altered platelet function resulting in either platelet hyper- or hyporeactivity may contribute to thrombotic or hemorrhagic complications. Different molecular changes have been identified that may underlie altered platelet activity and hemostasis in CKD. In this study, we summarize the knowledge on CKD-induced aberrations in hemostasis, with a special focus on platelet abnormalities. We also discuss how prominent alterations in vascular integrity, coagulation, and red blood cell count in CKD may contribute to altered hemostasis in these patients who are high risk. Furthermore, with patients with CKD commonly receiving antiplatelet therapy to prevent secondary atherothrombotic complications, we discuss antiplatelet treatment strategies and their risk versus benefit in terms of thrombosis prevention, bleeding, and clinical outcome depending on CKD stage. This reveals a careful consideration of benefits versus risks of antiplatelet therapy in patients with CKD, balancing thrombotic versus bleeding risk. Nonetheless, despite antiplatelet therapy, patients with CKD remain at high cardiovascular risk. Thus, deep insights into altered platelet activity in CKD and underlying mechanisms are important for the optimization and development of current and novel antiplatelet treatment strategies, specifically tailored to these patients who are high risk. Ultimately, this review underlines the importance of a closer investigation of altered platelet function, hemostasis, and antiplatelet therapy in patients with CKD.
慢性肾脏病(CKD)患者发生心血管和血栓栓塞并发症的风险显著增加,约一半的晚期 CKD 患者最终死于心血管疾病。矛盾的是,这些患者也有更高的出血风险,这大大增加了患者治疗的复杂性。血小板在止血中起着核心作用,导致血小板高反应性或低反应性的血小板功能改变可能导致血栓或出血并发症。已经确定了不同的分子变化,这些变化可能是 CKD 导致血小板活性和止血改变的基础。在本研究中,我们总结了关于 CKD 引起的止血异常的知识,特别关注血小板异常。我们还讨论了 CKD 中血管完整性、凝血和红细胞计数的显著改变如何导致这些高风险患者的止血改变。此外,由于 CKD 患者常接受抗血小板治疗以预防继发性动脉血栓并发症,我们讨论了抗血小板治疗策略及其在血栓预防、出血和临床结局方面的风险与获益,具体取决于 CKD 分期。这揭示了在 CKD 患者中抗血小板治疗的获益与风险的仔细考虑,平衡血栓形成与出血风险。尽管进行了抗血小板治疗,CKD 患者仍存在较高的心血管风险。因此,深入了解 CKD 中改变的血小板活性及其潜在机制对于优化和开发当前和新型抗血小板治疗策略非常重要,这些策略专门针对这些高风险患者。总之,本综述强调了更深入研究 CKD 患者改变的血小板功能、止血和抗血小板治疗的重要性。