New membranes based on polyethersulfone – SlipSkin™ polymer blends with low fouling and high blood compatibility

Hemodialysis is an important therapy for treating patients with End Stage Renal Disease (ESRD). These patients visit the hospital 3 times a week and each time their blood is cleansed during 4-hour dialysis sessions using a hollow fiber membrane module; also called artificial kidney. This device mainly achieves removal of small water-soluble toxins and a limited number of middle molecules. To improve the clearance of toxins, especially middle molecules and protein bound toxins, longer treatment via nocturnal dialysis and/or the application of portable/wearable artificial kidney is required. Such therapies require application of membranes with very low fouling and very good blood compatibility. Current membranes often contain hydrophilic additives which could elute during sterilization processes and/or during long-term filtration. In this study, we propose a simple method for developing low fouling blood compatible membranes by blending of polyethersulfone (PES), a material already used for fabrication of dialysis membranes, with small amounts of SlipSkin™ (SS), a blood compatible random copolymer of hydrophilic N-vinylpyrrolidone (NVP) and hydrophobic N-butylmethacrylate (BMA). Our results show that membranes with 2 wt% of SS have high fouling resistance to proteins and middle-size molecules and very good blood compatibility, making these membranes promising for application in dialysis therapy

Assessment and determinants of whole blood and plasma fibrinolysis in patients with mild bleeding symptoms

Enhanced clot lysis is associated with bleeding, but assessment of lysis capacity remains difficult. The plasma turbidity lysis and whole blood tissue Plasminogen Activator-Rotational Thromboelastometry (tPA-ROTEM) assays estimate fibrinolysis under more physiological conditions than clinically used assays. We hypothesized that these assays could find signs of enhanced lysis capacity in patients who report bleeding symptoms, but are not diagnosed with bleeding disorders. We also aimed to gain insight in determinants of the results of these lysis assays. Data from 240 patients with and 95 patients without self-reported bleeding symptoms were obtained, who were included in a study that primarily aimed to assess prevalence of haemostaticabnormalities in preoperative patients. ROTEM and turbidity assays were performed with rtPA. Blood counts, fibrinolysis and coagulation factor activities were determined. Data were analysed using multivariable linear regression models. Remarkably, patients reporting bleeding symptoms showed signs of significantly impaired lysis capacity in the tPA-ROTEM, but not in the turbidity lysis assay. In these patients, the tPA-ROTEM results depended on FII, FXII, plasminogen, α2-antiplasmin, PAI-1 and TAFI levels. The turbidity lysis results were significantly influenced by fibrinogen, α2-antiplasmin, PAI-1 and TAFI. In conclusion, the tPA-ROTEM and the turbidity lysis assay could not detect enhanced fibrinolytic capacity in patients with bleeding symptoms. This suggests that these symptoms are not caused by enhanced fibrinolytic activity. As both assays were sensitive to important determinants of fibrinolysis they may be able to detect a fibrinolytic imbalance, but this needs to be validated in patients with known hypo- or hyperfibrinolytic disorders