A 2022 systematic review and network meta-analysis assessed the efficacy and safety of anticoagulants for the treatment and prophylaxis of venous thromboembolism (VTE) in patients with renal dysfunction. This comprehensive analysis included 21 randomized controlled trials with a total of 76,574 participants, among whom 8,972 exhibited renal insufficiency, including VTE prophylaxis (N= 7 trials). In the prophylaxis of VTE, desirudin demonstrated a lower risk of VTE occurrence compared to enoxaparin, though it was associated with a higher bleeding risk. Conversely, betrixaban emerged as the most favorable anticoagulant for prophylaxis due to its superior safety and efficacy profile. Among the various anticoagulants studied, enoxaparin was specifically compared concerning its use in patients undergoing hemodialysis. Enoxaparin, when used in such patients, requires careful consideration due to potential challenges in balancing efficacy and the risk of bleeding. The analysis emphasized the necessity of adjusting anticoagulant regimens based on individual renal function to optimize treatment outcomes and minimize adverse effects, especially in high-risk groups such as those receiving hemodialysis. [1]
Data on enoxaparin use, specifically for deep vein thrombosis (DVT) prophylaxis in hemodialysis patients, is limited. Available research mainly investigated the efficacy of enoxaparin in reducing the incidence of recurrent vascular access stenosis in hemodialysis patients. While there are currently no recommendations for an anti-Xa trough level goal in patients with CrCl ≤30 mL/min, trends toward lower thromboembolism incidences and shorter hospital stays have been observed with reduced-dose enoxaparin therapy when compared to unfractionated heparin. Since enoxaparin is excreted predominantly by the kidneys, its half-life increases in patients receiving dialysis. Losses of low molecular weight heparins (LMWH) may occur at the start of high-flux dialysis and hemodiafiltration before the dialyzer membranes become protein-coated. Initially, LMWHs were able to be titrated to achieve a peak anti-Xa activity of 0.4-0.6 IU/ml, and ≤0.2 IU/ml at the end of dialysis; however, research indicates that frequency and duration of dialysis overall will affect LMWH usage. Some studies support the off-label use of enoxaparin, suggesting that prophylactic doses do not significantly increase bleeding risks and can be used without rigorous monitoring. This is in contrast to therapeutic doses, where empirical dose adjustments and biological monitoring are deemed necessary due to challenges in accurately predicting anticoagulation levels with anti-factor Xa, especially in patients with compromised renal function. Overall, tailored anticoagulation strategies are critical in high-risk populations, including those receiving DVT prophylaxis. [2], [3], [4]
A 2004 meta-analysis evaluated 17 randomized trials to compare the efficacy and safety of LMWH, including enoxaparin, with unfractionated heparin (UFH) for patients undergoing hemodialysis. The meta-analysis included data from 11 direct comparisons of LMWH and UFH, revealing no significant differences in bleeding incidents (relative risk [RR] 0.96; 95% confidence interval [CI] 0.27 to 3.43) or extracorporeal circuit thrombosis (RR 1.15; 95% CI 0.70 to 1.91) between the two treatments. While enoxaparin use for DVT prophylaxis was not assessed in the analysis for hemodialysis patients, no evidence of LMWH bioaccumulation with repeated doses was observed, indicating a stable anticoagulant effect without increasing bleeding risks. Despite the theoretical advantages of LMWH, such as predictable anticoagulation and a decreased risk of heparin-induced thrombocytopenia, the meta-analysis emphasized that larger, more rigorous trials are needed to draw definitive conclusions on the most effective anticoagulation strategy for patients with end-stage renal disease undergoing hemodialysis. [5]
A 2021 prospective cohort study investigated the potential accumulation of enoxaparin during hemodialysis with regional citrate anticoagulation in patients with acute kidney injury, aiming to address concerns about LMWHs accumulating in critically ill patients undergoing continuous renal replacement therapy (CRRT) managed by continuous veno-venous hemodialysis (CVVHD). A total of 29 adult patients from surgical ICUs were included, all receiving enoxaparin subcutaneously for VTE prophylaxis. Anti-Xa levels were measured at baseline and for three consecutive days during CRRT when enoxaparin had reached trough levels. In addition, modified assays of rotational thromboelastometry (ROTEM) were employed to detect subtle changes below the detection limit of conventional anti-Xa testing. Median anti-Xa trough levels remained below the detection limit of the test (<0.1 IU mL-1) throughout the study period, consistent across all four testing points, with interquartile ranges showing minimal variation. Furthermore, the modified ROTEM assays, known to be highly sensitive to LMWHs, did not reveal significant changes in parameters of clot initiation or formation dynamics from baseline to the final day of examination. Consequently, the study concluded that monitoring anti-Xa levels in this specific setting of CRRT with regional citrate anticoagulation may not be necessary, as evidence did not support the accumulation of enoxaparin in the patient cohort. [6]
Finally, a 2022 retrospective chart review examined the safety of enoxaparin for prophylaxis against DVT in patients with chronic kidney disease on hemodialysis. The study compared 200 hospitalized hemodialysis patients divided evenly into two groups: those receiving enoxaparin versus those receiving UFH. Enoxaparin was dosed at 30 mg subcutaneously every 48 hours, while UFH was given at 5,000 units subcutaneously every 8 hours. No statistical differences were observed in incidence of VTE, nor bleeding, between the two groups, including those over 65 years. Notably, there was no development of venous thromboembolism in either group during therapy. Although the overall incidence of bleeding was low, the enoxaparin group exhibited a higher decline in platelet counts compared to the UFH group. The need for packed red cell transfusions was slightly higher in the enoxaparin group (4 versus 2 in the UFH group), but this difference was not statistically significant. The data suggests that enoxaparin may be safe for DVT prophylaxis in hemodialysis patients, warranting further investigation. [7]