Hemodialysis without Systemic Anticoagulation: A Prospective Randomized Trial to Evaluate 3 Strategies in Patients at Risk of Bleeding

Abstract

ObjectiveIn this clinical trial, we aimed to compare three means of performing chronic hemodialysis in patients with contra-indication to systemic heparinization.MethodsThis open-label monocentric randomized « n-of-one » trial, conducted in a single tertiary care center, recruited chronic hemodialysis patients with a contra-indication to systemic heparinization for at least 3 consecutive sessions. All patients underwent hemodialysis with an AN69ST dialyzer, and were administered three alternative dialysis procedures in a random sequence: intermittent saline flushes, constant saline infusion, or pre-dialysis heparin coating of the membrane. The primary outcome was the need to interrupt the dialysis session because of clotting events due to either (i) a complete coagulation of the circuit; (ii) a partial coagulation of the circuit; (iii) a>50% rise over baseline in the venous pressure.ResultsAt the end of the inclusion period (May, 2007 to December, 2008), the number of patients to include (n = 75) was not reached: only 46 patients were included and underwent randomization. The study was terminated, and statistical analysis took into account 224 hemodialysis sessions performed in 44 patients with analyzable data. Heparin adsorption was associated with a significant reduction of the need to interrupt the dialysis session because of clotting events: odds ratio 0.3 (CI 95% 0.2 to 0.6; p<0.001, versus intermittent saline flushes). Heparin adsorption was also associated with higher odds for performing >3 h dialysis sessions and for having complete blood restitution. There were no significant effects of the dialysis procedure on weight loss, online ionic dialysance, and adverse events.ConclusionHeparin-coated AN69ST dialysis membrane is a safe and effective method to avoid or delay per-dialytic clotting events in patients with contra-indication to systemic anticoagulation. However, results are not generalizable safely to patients with active bleeding, since weak heparinemia, not assessed in this study, may occur.Trial RegistrationClinicalTrials.gov NCT00473109.

Cytokine-adsorbing hemofilter: old but new modality for septic acute kidney injury

“…Furthermore, the surface of the AN69ST membrane can be coated with heparin by priming with saline-containing heparin. As a consequence, the anti-thrombogenicity of the AN69ST membrane exceeds that of the native AN69 membrane and anticoagulant-free hemodialysis using AN69ST membrane has been reported [40,41]. On the other hand, as the sulfonyl groups on the AN69 membrane adsorb nafamostate mesilate, this anticoagulant is not compatible enough with the AN69/ AN69ST membrane [42].…”

Heparin‐free renal replacement therapy for chronic hemodialyzed patients at high risk for bleeding: a comparison of on‐line predilution hemodiafiltration with conventional hemodialysis

“…A major side effect is the occurrence of bloodline clotting which reduces the delivered dialysis dose and generates blood loss . The additional use of periodic saline rinse have improved ECC survival but it was shown in some studies that it increases coagulation markers and premature restitution frequency . Also, saline flushes if not associated to additional ultrafiltration rate may lead to hypervolemia.…”

“…A possible alternative is represented by the use of heparin‐coated membrane, a material that has the ability to bind heparin in its surface providing predominantly a local anticoagulation effect . Results were, however, equivocal; circuit coagulation was reported with a frequency varying from 5 to 50% and early termination of dialysis session from 5% to 7% . We routinely used a modified polyacrylonitrile membrane (AN69ST) for HD sessions.…”

“…Yet, the best management of heparin‐free RRT for chronic hemodialysis patients at risk of bleeding remains under scrutiny. Studies comparing different techniques and procedures in these settings are scarce . At the best of our knowledge, the effect of predilution free‐heparin HDF associated to an automatic controlled substitution has never been studied.…”

Comparison of the AN69ST Membrane versus Citrate-Enriched Dialysate on Clotting Events during Hemodialysis without Systemic Anticoagulation

“…Heparin-grafted membranes, compared to regular saline flushes, have been shown to be safe and useful method for patients at increased risk of bleeding, such as gastrointestinal bleeds, during invasive procedures, those at perioperative risk, or cerebral hemorrhage [25], [26]. A randomized study that included 48 hemodialyzed patients with a high risk of bleeding found that priming AN69ST with a heparinized saline infusion was more efficient than using an intermittent or continuous saline infusion to prevent blood clotting during HD sessions without anticoagulation [26]. Partial adsorption of heparin from the membrane and incomplete removal of the priming solution before connecting the patient to the extracorporeal circuit occur when using the heparin adsorption protocol, with subsequent systemic anticoagulation caused by circulating heparin.…”