Adverse Outcomes of Anticoagulant Use among Hospitalized Patients with Chronic Kidney Disease: A Comparison of the Rates of Major Bleeding Events between Unfractionated Heparin and Enoxaparin

Abstract

BackgroundAnticoagulation therapy is usually required in patients with chronic kidney disease (CKD) for treatment or prevention of thromboembolic diseases. However, this benefit could easily be offset by the risk of bleeding.ObjectivesTo determine the incidence of adverse outcomes of anticoagulants in hospitalized patients with CKD, and to compare the rates of major bleeding events between the unfractionated heparin (UFH) and enoxaparin users.MethodsOne year prospective observational study was conducted in patients with CKD stages 3 to 5 (estimated GFR, 10–59 ml/min/1.73 m2) who were admitted to the renal unit of Dubai Hospital. Propensity scores for the use of anticoagulants, estimated for each of the 488 patients, were used to identify a cohort of 117 pairs of patients. Cox regression method was used to estimate association between anticoagulant use and adverse outcomes.ResultsMajor bleeding occurred in 1 in 3 patients who received anticoagulation during hospitalization (hazard ratio [HR], 4.61 [95% confidence interval [CI], 2.05–10.35]). Compared with enoxaparin users, patients who received anticoagulation with unfractionated heparin had a lower mean [SD] serum level of platelet counts (139.95 [113]×103/µL vs 205.56 [123] ×103/µL; P<0.001), and had a higher risk of major bleeding (HR, 4.79 [95% CI, 1.85–12.36]). Furthermore, compared with those who did not receive anticoagulants, patients who did had a higher in-hospital mortality (HR, 2.54 [95% CI, 1.03–6.25]); longer length of hospitalization (HR, 1.04 [95% CI, 1.01–1.06]); and higher hospital readmission at 30 days (HR, 1.79 [95% CI, 1.10–2.91]).ConclusionsAnticoagulation among hospitalized patients with CKD was significantly associated with an increased risk of bleeding and in-hospital mortality. Hence, intensive monitoring and preventive measures such as laboratory monitoring and/or dose adjustment are warranted.

Anticoagulation Therapy in Patients with Chronic Kidney Disease

“…The study identified the incidence of major bleeding events from therapy with full-therapeutic doses of UFH, or with adjusted enoxaparin (1 mg/kg once daily), and compared the rates of major bleeding between the UFH and enoxaparin users. In this study, major bleeding occurred in 1 in 3 patients who received anticoagulation during hospital stay (hazard ratio /mL; P < 0.001) [35]. In the above mentioned studies, the risk of bleeding complication was higher with fulltherapeutic doses of UFH compared to enoxaparin.…”

“…For example, in a retrospective observational study of 7721 dialysis patients who received thrombophylaxis therapy with either UFH or enoxaparin, reported that enoxaparin was not associated with higher bleeding risk in comparison with UFH (risk ratio, 0.98; 95 % CI 0.78-1.23), concluding that thrombophylaxis doses of enoxaparin appeared to be safe and could be used as an alternative to UFH in dialysis patients [42]. More recently, in a prospective study for the treatment of thromboembolic events in hospitalized patients with CKD from stages 3-5, enoxaparin administrated in adjusted therapeutic doses was associated with lower bleeding events compared to UFH [35]. The results of the study highlighted the safety of enoxaparin when administered in therapeutic doses with dose adjustment for patients with severe CKD.…”

Treatment with Dalteparin is Associated with a Lower Risk of Bleeding Compared to Treatment with Unfractionated Heparin in Patients with Renal Insufficiency

“…Sharif-Askari et al compared patients with CKD stages 3-5 and noted a higher incidence of major bleeding with enoxaparin over UFH (HR4.79). 24 Thorevska and colleagues also reported an increased incidence of bleeding (2.54x) with therapeutic enoxaparin as compared to UFH 25 in patients with GFR < 60 mL/min. Levine et al showed a positive relationship between anti-factor Xa level and incidence of wound hematoma in hip replacement patients with once-daily prophylactic enoxaparin, 26 whereas Sanderlink et al showed that, after 5 days of enoxaparin prophylaxis, anti-factor Xa levels were found to be unrelated to renal function until CrCl < 20 mL/ min.…”

Enoxaparin utilization evaluation in inpatients with or at risk of thromboembolic disorders: A one-year, single-centered, retrospective Study

“…(10). Furthermore, since renal excretion is the main elimination route for enoxaparin, dose adjustment is required in patients with renal dysfunction, indicated by creatinine clearance of less than 30 ml/min (6,11). An assessment of the monitoring procedure revealed that anti Xa factor, and stool occult blood test were not measured for any of the patients included in this study indicating that the physicians did not consider these tests as part of the monitoring procedure.…”

“…It is the leading LMWH with the largest volume of published information on use in the setting of percutaneous coronary intervention (4) and the most widely studied LMWH for the prophylaxis/treatment of venous thromboembolism (VTE) (5). The ease of administration and the predictable anticoagulant effect of enoxaparin which eliminate the need for routine laboratory monitoring (4,(6)(7), relatively low cost and its wide availability (4) have led to wide applicability and general acceptability of the drug for the prophylaxis/treatment of thromboembolic disorders in most healthcare settings worldwide. Hence, it is a suitable candidate for DUE study.…”