Transfusion Medicine

Summary Mannan‐binding lectin (MBL) is a plasma collectin (C‐type lectin with a collagen‐like domain) and is considered an important component of innate immunity. Circulating MBL is genetically determined for the major part, but plasma concentration is also markedly influenced by nongenetic factors. The carbohydrate‐binding ability of MBL can be inhibited by simple sugars like mannose, fucose and N‐acetylglucosamine, but its greatest avidity appears to be for repeating mannose‐based structural patterns typical of microbial surfaces. By this means, MBL can bind to a wide variety of bacteria and other microbes, neutralizing them and/or opsonizing them by activating complement using the recently discovered lectin pathway of complement activation. Individual humans differ 1000‐fold in MBL concentration, and individuals with low circulating MBL appear to be more vulnerable to infections in a number of clinical settings, especially when combined with secondary immune deficiency. The best evidence that MBL deficiency or insufficiency is physiologically relevant comes from a rapidly expanding literature of clinical studies. MBL insufficiency appears to be a significant risk factor for infections in infants, and for individuals of any age undergoing chemotherapy or post‐transplant immunosuppression. Moreover, MBL appears to have a significant influence on the course of certain chronic diseases like rheumatoid arthritis and cystic fibrosis. Replacement therapy with a plasma‐derived product is safe and seems promising, while recombinant MBL provides hope for large‐scale therapeutic applications. Randomized clinical trials of MBL therapy, which are now on the horizon, should provide unambiguous evidence for the physiological significance of MBL in innate immunity.

Aim: In this study, we performed weekly assessment of morphology‐related parameters through monitoring of CPD‐SAGM leuco‐filtered erythrocyte concentrates from blood withdrawal until the 42nd day of storage.

Background: Liquid storage of red blood cells (RBCs) delivers a blood‐derived therapeutic, which is safe, available, effective and affordable for most patients who need transfusion therapy in developed countries. However, a growing body of accumulating controversial evidences, from either biochemical or retrospective clinical studies, prompted safety concerns about longer stored RBCs.

Methods: Statistical image analysis through scanning electron microscope was coupled to osmotic fragility and erythrocyte sedimentation rate.

Results: We could observe that by day 21 more than 50% of RBCs displayed non‐discocyte phenotypes. This observation was related to an increase in osmotic fragility, which was totally overlapped in day 0 controls and day 7 RBCs while only slightly augmented in day 14 samples. Cation dysregulation (pH internal/external alteration and potassium) might both reflect and trigger a negative feedback loop with metabolic fluxes and membrane cation pumps.

Conclusion: Morphology parameters suggest that significant alterations to RBC morphology over storage duration occur soon after the 14th day of storage, as to become significant enough within the 21st day.

Phthalates are the most widely used plasticisers in the world and have been in medical use since 1955. Di(2‐ethylhexyl)phthalate (DEHP) is present in many industrial and domestic products, and is a common plasticiser used in blood bags and tubing sets. Concerns have been raised by environmental groups that DEHP exposure may result in gender birth defects and the feminisation of boys although there were no studies performed of intravenous exposure to DEHP on higher mammals or humans which report similar effects.

This article reports on the toxicology of DEHP and considers concerns regarding its use in the context of transfusion medicine. The benefits of using DEHP are evaluated and the use of alternative plasticisers to DEHP is explored. The article reports on international and European regulatory recommendations for DEHP use in transfusion medicine and examines the impact of legislation on the medical devices and blood industries. The article also reviews labelling considerations for blood components and offers some guidance for blood establishments in respect of DEHP use.

Summary The identification of specific antimicrobial activity of intravenous immunoglobulin (IVIG) preparations against particular microbial pathogens can assist in determining their therapeutic potential for specific infectious diseases. We analysed five different commercial IVIG preparations for the presence of antibodies directed against a large panel of viral, bacterial, fungal and parasitic pathogens. All IVIG batches contained high activity against herpesviruses types 1, 2, 6 and 7, as well as against varicella zoster virus, Epstein‐Barr virus (EBV), measles, mumps, rubella and parvovirus B19. Some IVIG batches also had a significant activity against adenovirus and Saint Louis encephalitis virus. The IVIGs held high activity against several bacterial pathogens, including Mycoplasma pneumonia, Chlamydia pneumonia, Helicobacter pylori and tetanus. No activity was found against various parasitic and fungal pathogens. Our findings may provide further support for the use of IVIG for the prevention and treatment of infections caused by specific viral and bacterial pathogens.

summary Stem cells and their use in regenerative therapies are currently hot topics in both biology and medicine. For transfusion scientists the concept of cell therapy is not a new idea but rather a fundamental practice in this field. Bone marrow transplantation was pioneered in the 1960s and relies on the capacity of haemopoietic stem cells in the donated bone marrow to completely reconstitute the blood system of the recipient. Although this capacity of adult (or somatic) stem cells to regenerate the tissue from which they arise is extremely important, the isolation and cultivation of human embryonic stem cells (hESCs) have opened up the possibility to generate any cell or tissue of the body. This characteristic of hESC offers the hope of cell replacement and regenerative therapy for a whole array of diseases, many of which are currently untreatable. However, in order to understand the potential advantages and disadvantages of using stem cells in regenerative medicine, it is necessary to fully understand their origin, characteristics and potential. This review will concentrate particularly on hESCs and their derivation, characterization and capacity to differentiate into clinically useful tissue including haemopoietic lineages.

summary.  The goal of this research was to study the safety and the efficacy of transfusing citrate‐phosphate‐adenine anticoagulant‐preservative (CPDA‐1) RBC stored for up to 28 days to reduce donor exposures in premature infants. A prospective randomized two‐group study was conducted with very low‐birth‐weight premature infants that received at least one RBC transfusion during hospital stay. Neonates randomly assigned to Group 1 (26 infants) were transfused with CPDA‐1 RBC stored for up to 28 days; those assigned to Group 2 (26 infants) received CPDA‐1 RBC stored for up to 3 days. Demographic and transfusion‐related data were collected. Neonates from both groups showed similar demographics and clinical characteristics. The number of transfusions per infant transfused was 4·4 ± 4·0 in Group 1 and 4·2 ± 3·1 in Group 2, and the number of donors per infant transfused was 1·5 ± 0·8 (Group 1) and 4·3 ± 3·4 (Group 2), P < 0·001. RBC transfusions containing 29·7 ± 18·3 mmol L⁻¹ of potassium (RBC stored for up to 28 days) did not cause clinical or biochemical changes and reduced donor exposures by 70·2%, compared to transfusions containing 19·8 ± 12·3 mmol L⁻¹ of potassium (RBC stored for up to 3 days), P < 0·001. In conclusion, RBC stored for up to 28 days safely reduced donor exposures in premature infants.

summary Microarrays were designed to monitor the expression of many genes in parallel, providing substantially more information than Northern blots or reverse transcription polymerase chain reaction analysing one or few genes at a time. The large sequencing projects provided the content for detailed expression studies under a variety of stimuli and conditions. The human genome project identified around 30 000 human genes. Estimated number of protein products is, however, 10–30 times higher, mainly due to the alternative splicing and post‐translational modifications. The identification of gene functions requires both genomic and proteomic approaches, including protein microarrays, and numerous current microarray projects focus on deciphering gene expression patterns under a variety of conditions. Establishing the key genes and gene products for particular conditions opens the way for diagnostic applications using multiparameter, high‐throughput assays. This format can also accommodate existing blood screening assays, potentially providing a single testing platform. This review considers the progress in diagnostic microarrays in a wider context of in vitro diagnostics field.

Transmission of human cytomegalovirus (CMV) via transfusion (TT‐CMV) may still occur and remains a challenge in the treatment of immunocompromised CMV‐seronegative patients, e.g. after stem cell transplantation, and for low birthweight infants. Measures to reduce the risk of TT‐CMV have been evaluated in clinical studies, including leucocyte depletion of cellular blood products and/or the selection of CMV‐IgG‐negative donations. Studies in large blood donor cohorts indicate that donations from newly CMV‐IgG‐positive donors should bear the highest risk for transmitting CMV infections because they contain the highest levels of CMV‐DNA, and early CMV antibodies cannot neutralise CMV. Based on this knowledge, rational strategies to reduce the residual risk of TT‐CMV using leucoreduced blood products could be designed. However, there is a lack of evidence that CMV is still transmitted by transfusion of leucoreduced units. In low birthweight infants, most (if not all) CMV infections are caused by breast milk feeding or congenital transmission rather than by transfusion of leucoreduced blood products. For other patients at risk, no definitive data exist about the relative importance of alternative transmission routes of CMV compared to blood transfusion. As a result, only the conduction of well‐designed studies addressing strategies to prevent TT‐CMV and the thorough examination of presumed cases of TT‐CMV will achieve guidance for the best transfusion regimen in patients at risk.