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

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.

Keywords: CKD; DOAC; ESRD; anticoagulation; heparin; warfarin.

Figure 1

Evidence based algorithm for anticoagulation in patients with CKD [25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50].