Pathogen reduction/inactivation of products for the treatment of bleeding disorders:what are the processes and what should we say to patients?

Patients with blood disorders (including leukaemia, platelet function disorders and coagulation factor deficiencies) or acute bleeding receive blood-derived products, such as red blood cells, platelet concentrates and plasma-derived products. Although the risk of pathogen contamination of blood products has fallen considerably over the past three decades, contamination is still a topic of concern. In order to counsel patients and obtain informed consent before transfusion, physicians are required to keep up to date with current knowledge on residual risk of pathogen transmission and methods of pathogen removal/inactivation. Here, we describe pathogens relevant to transfusion of blood products and discuss contemporary pathogen removal/inactivation procedures, as well as the potential risks associated with these products: the risk of contamination by infectious agents varies according to blood product/region, and there is a fine line between adequate inactivation and functional impairment of the product. The cost implications of implementing pathogen inactivation technology are also considered

Two dimensional chromatographic characterization of block copolymers of 2-ethylhexyl acrylate and methyl acrylate, P2EHA-b-PMA, produced via RAFT-mediated polymerization in organic dispersion

For the precise characterization of block copolymers of 2-ethylhexyl acrylate (2EHA) and methyl acrylate (MA) produced via RAFT (reversible addition-fragmentation chain transfer)-mediated dispersion polymerization, novel liquid chromatographic separations have been developed. SEC showed multimodal molar mass distributions (MMD) and HPLC showed multimodal chemical composition distributions (CCD). The analyses of MMD and CCD of the reaction products indicated the formation of the expected block copolymer along with remaining P2EHA and PMA homopolymer fractions. Online coupling of SEC and gradient HPLC in a two-dimensional liquid chromatography (2D-LC) setup proved to be an efficient method to fractionate all polymer species present in the samples. Different kinds of copolymer molecules were identified in addition to the two homopolymers. The quantification of P2EHA using liquid chromatography at critical conditions (LC-CC) showed that the unreacted macro(RAFT agent) amount remained unchanged during at least the first 4 h of polymerization. LC-CC experiments also allowed the relative molar mass of the PMA blocks contained in the copolymers to be determined. The implementation of 2D-LC combining SEC and LC-CC allowed a more precise characterization of the different copolymer structures in particular in terms of block size. Finally, the results obtained by SEC/HPLC were confirmed by LC-1H NMR (proton nuclear magnetic resonance) experiments. It was concluded that the dispersed state of the polymerization system was the important factor for the formation of broadly distributed, complex copolymers when using a dithiobenzoate-based reactive macromolecular stabilizer. The detailed characterization of the system highlighted the enhancement of irreversible termination at the interface of the dispersed particles. © 2010 American Chemical Society.Articl

Blood neutrophil bactericidal activity against methicillin-resistant and methicillin-sensitive Staphylococcus aureus during cardiac surgery.

Whether methicillin-resistant Staphylococcus aureus (MRSA) constitutes per se an independent risk factor for morbidity and mortality after surgery as compared with methicillin-sensitive Staphylococcus aureus (MSSA) remains a subject of debate. The aim of this study was to assess whether innate defenses against MRSA and MSSA strains are similarly impaired after cardiac surgery. Both intracellular (isolated neutrophil functions) and extracellular (plasma) defenses of 12 patients undergoing scheduled cardiac surgery were evaluated preoperatively (day 0) and postoperatively (day 3) against two MSSA strains with a low level of catalase secretion and two MRSA strains with a high level of catalase secretion, inasmuch as SA killing by neutrophils relies on oxygen-dependent mechanisms. After surgery, an increase in plasma concentration of IL-10, an anti-inflammatory cytokine able to inhibit reactive oxygen species secretion and bactericidal activity of neutrophils, was evidenced. Despite the fact that univariate analysis suggested a specific impairment of neutrophil functions against MRSA strains, two-way repeated-measures ANOVA failed to demonstrate that the effect of S. aureus phenotype was significant. On the other hand, an increase in type-II secretory phospholipase A2 activity, a circulating enzyme involved in SA lysis, was evidenced and was associated with an enhancement of extracellular defenses (bactericidal activity of plasma) against MRSA. Overall, cardiac surgery and S. aureus phenotype had a significant effect on plasma bactericidal activity. Cardiac surgery was characterized by enhanced antibacterial defenses of plasma, whereas neutrophil killing properties were reduced. The overall effect of S. aureus phenotype on neutrophil functions did not seem significant