Association Between Low-Molecular-Weight Heparin and Risk of Bleeding Among Hemodialysis Patients: A Retrospective Cohort Study

Abstract

Background:Low-molecular-weight heparins (LMWH) replaced unfractionated heparin (UFH) in multiple indications. Although LMWH efficacy in hemodialysis was demonstrated through multiple studies, their safety remains controversial. The potential bioaccumulation in patients undergoing chronic hemodialysis raised the question of bleeding risk among this population.Objective:The aim of this study was to evaluate bleeding risk among patients with chronic hemodialysis receiving LMWH or UFH for the extracorporeal circuit anticoagulation.Design:We conducted a retrospective cohort study on data extracted from the Régie de l’assurance maladie du Québec (RAMQ) and Med-Echo databases from January 2007 to March 2013.Setting:Twenty-one hemodialysis centers in the province of Québec, Canada.Patients:Chronic hemodialysis patients.Measurements:Bleeding risk evaluated by proportional Cox model for time-dependent exposure using demographics, comorbidities, and drug use as covariates.Methods:Minor, major, and total bleeding events identified using International Classification of Diseases, Ninth Revision (ICD-9)/International Classification of Diseases, Tenth Revision (ICD-10) codes in the RAMQ and Med-Echo databases. Exposure status to LMWH or UFH was collected through surveys at the facility level.Results:We identified 5322 prevalent and incident patients with chronic hemodialysis. The incidence rate for minor, major, and total bleeding was 9.45 events/1000 patient-year (95% confidence interval [CI]: 7.61-11.03), 24.18 events/1000 patient-year (95% CI: 21.52-27.08), and 32.88 events/1000 patient-year (95% CI: 29.75-36.26), respectively. We found similar risks of minor adjusted hazard ratio (HR: 1.04; 95% CI: 0.68-1.61), major (HR: 0.83; 95% CI: 0.63-1.10), and total bleeding (HR: 0.90; 95% CI: 0.72-1.14) when comparing LMWH with UFH.Limitations:Potential misclassification of patients’ exposure status and possible underestimation of minor bleeding risk.Conclusion:LMWH was not associated with a higher minor, major, or total bleeding risk. LMWH did not increase the risk of bleeding compared with UFH for the extracorporeal circuit anticoagulation in hemodialysis. The convenience of use and predictable effect made LMWH a suitable alternative to UFH in hemodialysis.

Effects of Changing Anticoagulation with Unfractionated Heparin into Enoxaparin in Hemodialysis Patients:Prospective Non Randomized Unicentre Study

“…The question of safety of the LMWH was addressed in the current study and there was no critical issue regarding safety during the duration of observation. In support to this, Lazrak and his associates [3] stated that LMWH was shown to be at least as safe as UFH for ECC anticoagulation in chronic HD Additionally, Lazrak and his Colleagues reported that LMWH was not associated with a higher minor, major, or total bleeding risk, and LMWH did not increase the risk of bleeding compared with UFH for the ECC anticoagulation in HD [12].…”

Using dalteparin in quotidian and nocturnal hemodialysis patients: A prospective study

“…Previous studies have demonstrated the safety of using dalteparin in the HD setting. There was no reporting of increased bleeding risk in two large cohort studies . Furthermore, Lutkin et al showed that dalteparin is safe and effective in pediatric home HD patients …”

“…Routine anticoagulation is required during hemodialysis (HD) treatments to prevent dialyzer and extracorporeal circuit clotting . In North America, the anticoagulant of choice for conventional thrice weekly HD therapies is unfractionated heparin (UFH), whereas in Western Europe, it is low‐molecular weight heparin (LMWH) . The advantages of UFH are its long history of use and short half‐life.…”

Anticoagulation in hemodialysis: A narrative review

“…Although the anticoagulant effect of LMWH can be monitored with factor Xa levels, clinical utility is limited as levels may not correlate with biological effect (i.e., clinically significant hemorrhage), and it is impractical to have separate assays for each agent 81,82 . Multiple analyses have demonstrated no increased risk of major bleeding or time to first major bleed with the use of LMWH compared to UFH, with reduced risk in some studies 39,83,84 A meta‐analysis demonstrated similar dialysis efficacy and circuit thrombosis between LMWH and UFH, though thorough analysis of bleeding events was limited by the small number of available studies 85 . A follow‐up meta‐analysis of head‐to‐head trials was conducted by Lazrak and colleagues to evaluate bleeding risk, demonstrating a relative risk of 0.76 for combined major and minor bleeding 86 .…”

“…A follow‐up meta‐analysis of head‐to‐head trials was conducted by Lazrak and colleagues to evaluate bleeding risk, demonstrating a relative risk of 0.76 for combined major and minor bleeding 86 . A small increase in minor bleeding events was observed for patients taking oral anticoagulants while dialyzing with LMWH as compared to UFH, 83 though an additional study supports the safety of using LMWH for HD in the setting of chronic oral anticoagulation 39 …”