Dana V. Devine

Liposome—complement interactions in rat serum: implications for liposome survival studies

Serum complement opsonizes particles such as bacteria for clearance by the reticuloendothelial system. Complement has been reported to interact with liposomes and therefore may mediate the reticuloendothelial system clearance of liposomes. This study has used a rat serum model to define some of the characteristics of liposomes which modulate their ability to activate complement. Using functional hemolytic assays and C3/C3b crossed immunoelectrophoresis, we have demonstrated that liposomes activated rat complement in a dose-dependent manner with higher concentrations of liposomes activating higher levels of complement. The detection of complement activation required the inclusion of phospholipids bearing a net charge. Complement activation occurred via the classical pathway; no alternative pathway activation was detected. The presence of cholesterol contributed to complement activation in a dose-dependent manner. Phospholipid fatty acyl chain length did not influence complement activation while the introduction of unsaturated acyl chains markedly decreased levels of complement activation. Liposome size also influenced complement activation with 400 nm unilamellar vesicles more effectively activating complement than 50 nm vesicles for equivalent amounts of exposed lipid. These studies demonstrate that the composition of the liposome greatly affects the in vitro activation of rat serum complement and suggest that the biological half-life of liposomes in the circulation of rats may be altered by changing the liposome composition to reduce complement activation.

Challenges in the management of the blood supply

Although blood suppliers are seeing short-term reductions in blood demand as a result of initiatives in patient blood management, modelling suggests that during the next 5-10 years, blood availability in developed countries will need to increase again to meet the demands of ageing populations. Increasing of the blood supply raises many challenges; new approaches to recruitment and retainment of future generations of blood donors will be needed, and care will be necessary to avoid taking too much blood from these donors. Integrated approaches in blood stock management between transfusion services and hospitals will be important to minimise wastage--eg, by use of supply chain solutions from industry. Cross-disciplinary systems for patient blood management need to be developed to lessen the need for transfusion--eg, by early identification and reversal of anaemia with haematinics or by reversal of the underlying cause. Personalised medicine could be applied to match donors to patients, not only with extended blood typing, but also by using genetically determined storage characteristics of blood components. Growing of red cells or platelets in large quantities from stem cells is a possibility in the future, but challenges of cost, scaling up, and reproducibility remain to be solved.

The Platelet Storage Lesion

The gradual loss of quality in stored platelets as measured collectively with various metabolic, functional, and morphologic in vitro assays is known as the platelet storage lesion. With the advent of pathogen reduction technologies and improved testing that can greatly reduce the risk for bacterial contamination, the platelet storage lesion is emerging as the main challenge to increasing the shelf life of platelet concentrates. This article discusses the contribution of platelet production methods to the storage lesion, long-established and newly developed methods used to determine platelet quality, and the significance for clinical transfusion outcome. Highlighted are the novel technologies applied to platelet storage including platelet additive solutions and pathogen inactivation.

Red blood cell hemolysis during blood bank storage: using national quality management data to answer basic scientific questions

BACKGROUND: Hemolysis of red blood cells (RBCs) during blood bank storage is the most obvious manifestation of RBC storage system failure. However, its analysis is made difficult because the largest source of interunit difference is donor specific. Availability of data from national blood systems on large numbers of RBC units used for internal quality control (QC) purposes and stored and processed in uniform ways permits statistical analysis.

Comprehensive proteomic analysis of protein changes during platelet storage requires complementary proteomic approaches.

BACKGROUND: Proteomics methods may be used to analyze changes occurring in stored blood products. These data sets can identify processes leading to storage‐associated losses of blood component quality such as the platelet (PLT) storage lesion (PSL). The optimal strategy to perform such analyses to obtain the most informative data sets, including which proteomics methods, is undefined. This study addresses relative differences among proteomics approaches to the analysis of the PLT storage lesion.

Translation of glycoprotein IIIa in stored blood platelets

BACKGROUND: Platelet (PLT) products have a short shelf life (5 days) owing in part to the deterioration of the quality of PLTs stored at 22°C. This creates significant inventory challenges, and blood banks may suffer shortages and high wastage as a result. The precise biochemical pathways involved in the PLT storage lesion are unknown and must be understood before storage time can be extended.

Hydrophobically derivatized hyperbranched polyglycerol as a human serum albumin substitute

There is a huge clinical demand for Human Serum Albumin (HSA), with a world market of approximately

BLOOD COMPONENTS: Red blood cell hemolysis during blood bank storage: using national quality management data to answer basic scientific questions

1.5B/year. Concern over prion and viral transmission in the blood supply has led to a need for safer substitutes and offers the opportunity for development of materials with enhanced properties over the presently available plasma expanders. We report here the synthesis and testing of a new synthetic plasma expander that can replace not only the osmotic and volume expansion properties of HSA but, uniquely, its binding and transport properties. We have synthesized several hyperbranched polyglycerols derivatized with hydrophobic groups and short poly(ethylene glycol) (PEG) chains. The hydrophobic groups provide regions for binding fatty acids and other hydrophobic materials while PEG imparts the necessary protection from host defense systems and enhances circulation longevity. These polymers, being hyperbranched, have only a small effect on plasma viscosity. We have shown in vitro that our materials bind 2-3 moles palmitic acid per mole, do not activate the platelet, coagulation or complement systems and do not cause red cell aggregation. In mice these materials are non-toxic with circulation half-lives as high as 34h, controllable by manipulating the molecular weight and the degree of PEG derivatization.

A comparative study of common techniques used to measure haemolysis in stored red cell concentrates

BACKGROUND: Hemolysis of red blood cells (RBCs) during blood bank storage is the most obvious manifestation of RBC storage system failure. However, its analysis is made difficult because the largest source of interunit difference is donor specific. Availability of data from national blood systems on large numbers of RBC units used for internal quality control (QC) purposes and stored and processed in uniform ways permits statistical analysis.

Implementation of buffy coat platelet component production: comparison to platelet-rich plasma platelet production

Background and Objectives  There is no standardized method of measuring the parameters for haemolysis determination of red cell concentrate (RCC). Three haemoglobin quantification methods (automated analyser, Harboe and Drabkin’s) and two methods of haematocrit measurement (automated analyser and microcapillary centrifugation) were evaluated for use with RCC.