Impact of anion exchange adsorbents on regional citrate anticoagulation.

INTRODUCTION: Heparin and citrate are commonly used anticoagulants in membrane/adsorption based extracorporeal liver support systems. However, anion exchange resins employed for the removal of negatively charged target molecules including bilirubin may also deplete these anticoagulants due to their negative charge. The aim of this study was to evaluate the adsorption of citrate by anion exchange resins and the impact on extracorporeal Ca2+ concentrations. METHODS: Liver support treatments were simulated in vitro. Citrate and Ca2+ concentrations were measured pre and post albumin filter as well as pre and post adsorbents. In addition, batch experiments were performed to quantify citrate adsorption. RESULTS: Pre albumin filter target Ca2+ concentrations were reached well with only minor deviations. Citrate was adsorbed by anion exchange resins, resulting in a higher Ca2+ concentration downstream of the adsorbent cartridges during the first hour of treatment. CONCLUSIONS: The anion exchange resin depletes citrate, leading to an increased Ca2+ concentration in the extracorporeal circuit, which may cause an increased risk of clotting during the first hour of treatment. An increase of citrate infusion during the first hour of treatment should therefore be considered to compensate for the adsorption of citrate.

Blood Compatibility-An Important but Often Forgotten Aspect of the Characterization of Antimicrobial Peptides for Clinical Application.

Acylation of antimicrobial peptides mimics the structure of the natural lipopeptide polymyxin B, and increases antimicrobial and endotoxin-neutralizing activities. In this study, the antimicrobial properties of lactoferrin-based LF11 peptides as well as blood compatibility as a function of acyl chain length were investigated. Beyond the classical hemolysis test, the biocompatibility was determined with human leukocytes and platelets, and the influence of antimicrobial peptides (AMPs) on the plasmatic coagulation and the complement system was investigated. The results of this study show that the acylation of cationic peptides significantly reduces blood tolerance. With increasing acyl chain length, the cytotoxicity of LF11 peptides to human blood cells also increased. This study also shows that acylated cationic antimicrobial peptides are inactivated by the presence of heparin. In addition, it could be shown that the immobilization of LF11 peptides leads to a loss of their antimicrobial properties.

In vitro investigations of citrate clearance with different dialysis filters.

OBJECTIVE: In extracorporeal blood purification, citrate anticoagulation offers several substantial advantages over conventional heparin anticoagulation. However, there is still a lack of information on citrate kinetics, especially on the citrate clearance of conventional hemodialyzers. The aim of this study was to investigate the citrate clearance for different hemodialysis filters as a basis for the development of an intelligent citrate-calcium infusion algorithm. MATERIALS AND METHODS: For our experiments, the Fresenius 4008H dialysis machine and the dialysis filters FX 60, F6 HPS, F8 HPS (Fresenius Medical Care, Bad Homburg, Germany), Polyflux 140H and 14L (Gambro Holding, Stockholm, Sweden), Xenium 130 (Baxter AG, Vienna, Austria) and APS-650 (ASAHI Kasei Kuraray Medical, Chiyoda-ku, Japan) were used. Clearance calculations were performed based on plasma/blood flow rate and the citrate concentrations at filter inlet and outlet. All experiments were carried out in vitro with fresh frozen plasma (FFP) or whole blood. RESULTS: The results prove that citrate clearance is significantly higher with high-flux filters than with low-flux filters. Higher dialysate flow rates cause a more effective removal of citrate. The citrate clearance for low-flux and high-flux filters was 71 ± 7 and 86 ± 1% of the urea clearance, respectively. CONCLUSIONS: Citrate can efficiently be removed with standard hemodialysis. However, depending on the infused amounts as well as on the patient - especially in patients with impaired liver function - the use of a high-flux dialysis filter and a high dialysate flow rate should be considered to minimize the risk of citrate accumulation.