Anticoagulation in combined membrane/adsorption systems

For extracorporeal blood purification treatments, an effective anticoagulation is needed to avoid contact activation via the intrinsic pathway of the blood-clotting system. While heparin is the standard anticoagulant in dialysis, it shows some disadvantages which have to be considered when it is used in membrane/adsorption-based blood purification systems. An alternative option for anticoagulation in these systems is citrate, which is effective as an anticoagulant by reducing the ionized calcium concentration in the extracorporeal circuit. However, to avoid citrate accumulation in the patient during treatment, the amount of citrate infusion and the citrate removal by the patient's metabolism as well as by dialysis have to be taken into consideration. The aim of this study was to elucidate the characteristics of heparin removal in membrane/adsorption-based blood purification systems, to find the correct way to pre-coat adsorbents in order to avoid excessive adsorption of heparin by anionic exchanging resins, and also to find an appropriate dosage of heparin for treatments with these systems to ensure patient safety. A further aim was to find the correct ionized calcium concentration to suppress complement activation, and to compare different dialysis filters regarding their citrate clearance in order to be able to recommend the correct dialysis setup to achieve appropriate citrate clearance. We were able to show that the adsorptive removal of heparin can be significantly reduced by pre-coating the adsorbents with heparin without a perceptible impact on the adsorption kinetics of bilirubin. Furthermore, we recommend the use of unfractionated heparin due to its lower sieving coefficient and therefore lower removal compared to fractionated heparins. Reducing the extracorporeal Ca(2+) concentration to 0.2 mmol/L by infusion of citrate solution to the extracorporeal circuit results in an effective suppression of the complement activation. To avoid citrate accumulation, we recommend the use of high flux filters when citrate anticoagulation is applied.