终末期肾病患者的抗凝治疗:一项批判性综述。

Anticoagulation in Patients with End-Stage Renal Disease: A Critical Review.

作者信息

Parul Fnu, Ratnani Tanya, Subramani Sachin, Bhatia Hitesh, Ashmawy Rehab Emad, Nair Nandini, Manchanda Kshitij, Anyagwa Onyekachi Emmanuel, Kaka Nirja, Patel Neil, Sethi Yashendra, Kavarthapu Anusha, Padda Inderbir

机构信息

PearResearch, Dehradun 248001, India.

Department of Medicine, University of Michigan Health-Sparrow Hospital, Michigan State University, Lansing, MI 48912, USA.

出版信息

Healthcare (Basel). 2025 Jun 8;13(12):1373. doi: 10.3390/healthcare13121373.

Abstract

BACKGROUND

Chronic kidney disease (CKD) and its advanced stage, end-stage renal disease (ESRD), affect millions worldwide and are associated with a paradoxical hemostatic imbalance-marked by both increased thrombotic and bleeding risks-which complicates anticoagulant use and demands clearer, evidence-based clinical guidance.

DESIGN

This study is a critical review synthesizing the current literature on anticoagulant therapy in CKD and ESRD, with emphasis on altered pharmacokinetics, clinical complications, and therapeutic adjustments.

DATA SOURCES

PubMed, Scopus, and Google Scholar were searched for articles discussing anticoagulation in CKD/ESRD, focusing on pharmacokinetics, clinical outcomes, and dosing recommendations.

STUDY SELECTION

Studies examining the safety, efficacy, and pharmacokinetics of anticoagulants-including heparin, low-molecular-weight heparin (LMWH), warfarin, and direct oral anticoagulants (DOACs)-in CKD and ESRD populations were included.

DATA EXTRACTION AND SYNTHESIS

Key findings were summarized to highlight the dose modifications, therapeutic considerations, and clinical challenges in managing anticoagulation in CKD/patients with ESRD. Emphasis was placed on balancing thrombotic and bleeding risks and identifying gaps in existing guidelines.

RESULTS

Patients with CKD and ESRD exhibit a paradoxical hypercoagulable state marked by platelet dysfunction, altered coagulation factors, and vascular endothelial damage. This condition increases the risk of thrombotic events, such as deep vein thrombosis (DVT) and pulmonary embolism (PE), while simultaneously elevating bleeding risks. Hemodialysis and CKD-associated variables further complicate the management of coagulation. Among anticoagulants, unfractionated heparin (UFH) is preferred due to its short half-life and adjustability based on activated partial thromboplastin time (aPTT). Low-molecular-weight heparins (LMWHs) offer predictable pharmacokinetics but require dose adjustments in CKD stages 4 and 5 due to reduced clearance. Warfarin necessitates careful dosing based on the estimated glomerular filtration rate (eGFR) to maintain an international normalized ratio (INR) ≤ 4, minimizing bleeding risks. Direct oral anticoagulants (DOACs), particularly Apixaban, are recommended for patients with eGFR < 15 mL/min or those on dialysis, although data on other DOACs in CKD remain limited. The lack of comprehensive guidelines for anticoagulant use in CKD and ESRD highlights the need for individualized, patient-centered approaches that account for comorbidities, genetics, and clinical context.

CONCLUSIONS

Managing anticoagulation in CKD/ESRD is challenging due to complex coagulation profiles and altered pharmacokinetics. Judicious dosing, close monitoring, and patient-centered care are critical. High-quality randomized controlled trials are needed to establish clear guidelines and optimize therapy for this vulnerable population.

摘要

背景

慢性肾脏病(CKD)及其晚期阶段终末期肾病(ESRD)影响着全球数百万人,并且与一种矛盾的止血失衡相关——其特征是血栓形成风险和出血风险均增加——这使得抗凝治疗变得复杂,需要更清晰、基于证据的临床指导。

设计

本研究是一项批判性综述,综合了关于CKD和ESRD抗凝治疗的当前文献,重点关注药代动力学改变、临床并发症和治疗调整。

数据来源

检索了PubMed、Scopus和谷歌学术,以查找讨论CKD/ESRD抗凝治疗的文章,重点关注药代动力学、临床结果和给药建议。

研究选择

纳入了研究CKD和ESRD人群中抗凝剂(包括肝素、低分子肝素(LMWH)、华法林和直接口服抗凝剂(DOAC))的安全性、有效性和药代动力学的研究。

数据提取与综合

总结了主要研究结果,以突出CKD/ESRD患者抗凝管理中的剂量调整、治疗考虑因素和临床挑战。重点在于平衡血栓形成和出血风险,并找出现有指南中的差距。

结果

CKD和ESRD患者表现出一种矛盾的高凝状态,其特征为血小板功能障碍、凝血因子改变和血管内皮损伤。这种情况增加了血栓形成事件的风险,如深静脉血栓形成(DVT)和肺栓塞(PE),同时也增加了出血风险。血液透析和与CKD相关的变量使凝血管理更加复杂。在抗凝剂中,普通肝素(UFH)因其半衰期短且可根据活化部分凝血活酶时间(aPTT)进行调整而更受青睐。低分子肝素(LMWH)具有可预测的药代动力学,但由于清除率降低,在CKD 4期和5期需要调整剂量。华法林需要根据估计的肾小球滤过率(eGFR)谨慎给药,以维持国际标准化比值(INR)≤4,将出血风险降至最低。对于eGFR<15 mL/min的患者或接受透析的患者,推荐使用直接口服抗凝剂(DOAC),尤其是阿哌沙班,尽管关于其他DOAC在CKD中的数据仍然有限。CKD和ESRD中抗凝剂使用缺乏全面指南,凸显了需要采用个体化、以患者为中心的方法,该方法要考虑合并症、遗传学和临床背景。

结论

由于复杂的凝血情况和药代动力学改变,CKD/ESRD患者的抗凝管理具有挑战性。明智的给药、密切监测和以患者为中心的护理至关重要。需要高质量的随机对照试验来建立明确的指南,并优化针对这一脆弱人群的治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bc/12193158/90399d57ce99/healthcare-13-01373-g001.jpg

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