An Adjustable Dalteparin Sodium Dose Regimen for the Prevention of Clotting in the Extracorporeal Circuit in Hemodialysis: A Clinical Trial of Safety and Efficacy (the PARROT Study)

Abstract

Background:Dalteparin sodium, a low-molecular-weight heparin, is indicated for prevention of clotting in the extracorporeal circuit during hemodialysis (HD). Product labeling recommends a fixed single-bolus dose of 5000 international units (IU) for HD sessions lasting up to 4 hours, but adjustable dosing may be beneficial in clinical practice.Objective:The aim of the PARROT study was to investigate the safety and efficacy of an adjustable dose of dalteparin in patients with end-stage renal disease requiring 3 to 4 HD sessions per week.Design:A 7-week, open-label, multicenter study with a single treatment arm, conducted between October 2013 and March 2016.Setting:Ten sites in Canada.Patients:A total of 152 patients with end-stage renal disease requiring 3 to 4 HD sessions per week.Measurements:The primary outcome was the proportion of HD sessions completed without premature termination due to inadequate anticoagulation.Methods:All participants initially received a dose of 5000 IU dalteparin, which could be adjusted at subsequent HD sessions when clinically indicated, by increment or decrement of 500 or 1000 IU, with no specified dose limits.Results:Patients were followed for 256 patient-months. Nearly all (99.9%; 95% confidence interval [CI]: 99.7-100) evaluable HD sessions were completed without premature clotting. Dose was adjusted for more than half (52.3%) of participants, mostly owing to clotting or access compression time >10 minutes. Median dalteparin dose was 5000 IU (range: 500-13 000 IU). There were no major bleeds, and minor bleeding was reported in 2.3% of all HD sessions. There was no evidence of bioaccumulation.Limitations:This short-term study, with a single treatment arm, was designed to optimize dalteparin dose using a flexible dosing schedule; it was not designed to specifically evaluate dalteparin dose minimization, provide a direct comparison of dalteparin versus unfractionated heparin, or provide information on long-term safety for flexible dalteparin dosing. Patients were excluded if they were at high risk of bleeding, including those on anticoagulants and those on antiplatelet agents other than aspirin <100 mg/d.Conclusions:Overall, an adjustable dalteparin sodium dose regimen allowed safe completion of HD, with clinical benefits over fixed dosing.Trial Registration:ClinicalTrials.gov NCT01879618, registered June 13, 2013.

Efficacy of enoxaparin in preventing coagulation during high-flux haemodialysis, expanded haemodialysis and haemodiafiltration

“…Post-dialysis aXa values were 0.26 ± 0.02 in HF-HD, 0.21 ± 0.02 in HDF and 0.22 ± 0.01 in HDx. These findings are similar to those of other studies [ 29 ] and conform to the standards for thrombosis avoidance. There were significant differences in post-dialysis aXa activity between HF-HD and HDF (0.26 ± 0.02 versus 0.21 ± 0.02, respectively; P = 0.024), which was most likely the result of enoxaparin removal during HDF, as has been previously described [ 14 ].…”

“…Some authors have suggested an aXa target range of <0.4 IU/mL [ 13 ], which is lower than the recommendations for aXa activity in the initial treatment of thrombosis (0.4–0.6 IU/mL) [ 28 ] and similar to the target for patients with an elevated risk of bleeding (i.e. 0.2–0.4 IU/mL) [ 2 , 29 ]. In our study, all pre-dialysis aXa activity levels were below the anticoagulation dose limit, which indicated no previous heparin interference.…”

Expanded hemodialysis: Is anticoagulation of the dialysis circuit different from online hemodiafiltration and high‐flux hemodialysis?

“…Although the end‐dialysis target for aXa has not been clearly established, some reports have suggested a target of >0.4 IU/mL [12,15,16,27]. In our study, however, the end‐dialysis target for aXa was, in all cases, in accordance with that of other authors, who recommended aXa < 0.4 IU/mL [17,18], which is lower than the recommendations for aXa in the initial treatment of thrombosis (0.4–0.6 IU/mL) [27,28] and similar to the target for patients with an elevated risk of bleeding (i.e., 0.2–0.4 IU/mL) [2,29,30]. Thus, our study points out that using the venous port with low doses of enoxaparin is safe; however, patients at high‐risk of bleeding were excluded, and only one session in each arm of treatment was conducted; therefore, more studies are needed in this regard.…”

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 …”