Storage of red blood cell concentrates: Clinical impact.

The storage of red blood cells for transfusion purposes induces modifications of biochemical and biological properties. Moreover, these modifications are modulated by the donors' characteristics and the cell processing. These ex vivo alterations were suspected to decrease the transfusion efficiency and even to induce adverse events. This short article will review the red blood cells storage lesions and the clinical data related to them. In particular, the questions regarding the donors and recipients sex will be discussed.

Transfusion medicine: Overtime paradigm changes and emerging paradoxes.

This essay aims to discuss some aspects of blood transfusion in the perspective of the changes that occurred over time as well as modifications of the paradigms that transformed the activities and the organization of blood transfusion services. Without specific knowledge, pioneers envisioned precision and personalized medicine, rendering transfusion medicine operational. Transfusion medicine is like The Picture of Dorian Grey: always young despite being old and sometimes appearing old-fashioned. Over the years, the transfusion medicine discipline has evolved, and major progress has been achieved, despite some troublesome periods (for example, the tainted blood scandal, and-at the time being-the offending plasma market and the selling of human parts). Transfusion medicine has at all times implemented the rapidly developing biomedical technologies to secure blood components. The safety of blood components has now reached an exceptional level in economically wealthy countries, especially compared to other health care disciplines. Strengthening of the safety has mandated that blood donors and recipients are unrelated, an issue which has eased preservation and fractionation practices; blood is no longer arm-to-arm transfused and neither is whole blood, the commonest component. However, it is interesting to note that a revival is occurring as whole blood is back on stage for certain specific indications, which is one among the many paradoxes encountered while studying this discipline.

Blood, perceptions, resource and ownership: When transfusion illustrates the complexity.

Blood is apart from the rest of the tissues as this fluid is overseen by basic and applied life and humanistic sciences. Blood is the essence of human functioning. It is the object of one of the most commonly known cancers, leukemia. It is life-saving in transfusion - a property that also gives blood a special credit and questions blood as a valuable merchandise or as no ones' property but common good. But blood is also scandalous after the tainted blood affair in the 1980s and 1990s. Blood is further inseparable from most religious practices, both forefront and hidden (magic cults). It is frightening as it is versed in legitimate and illegitimate combats; it is poured to compensate offenses or debts in many civilizations. Any time blood comes forefront, rationale science leaves it to irrational digressions. Even the very same life-saving transfusion, is beaten by groups of opponents on religious grounds. Further, at a time blood cells and molecules are scrutinized, no one can claim having a complete understanding of what blood is, off the vasculature, as - to study it - one has to alter it. The study of blood is fascinating for all colleges of an academy and not many topics can share this property: chemists, physicists, geneticists, physiologists, medical doctors, philosophers, ethicists, theologians, artists, historicists, anthropologists, sociologists, etc. have all contributed to depict different, specific, aspects of blood. The present review aims at merging different aspects of blood to give pathophysiologists a platform to better understand fears and hopes related to this special tissue, when dealing with patients of theirs.

Irreversible oxidations of platelet proteins after riboflavin-UVB pathogen inactivation.

Pathogen inactivation technologies are known to alter in vitro phenotype and functional properties of platelets. Because pathogen inactivation generates reactive oxygen species, oxidative stress is considered as one of the plausible cause at the origin of the platelet storage lesion acceleration after treatment. To date proteomics has been used to document the protein variations to picture out the impact. Here, platelet concentrates were prepared from buffy-coats in Intersol additive solution, leukoreduced and pathogen inactivated using a riboflavin/UVB treatment. At day 2 of storage the platelet proteomes of control (untreated) and treated platelet concentrates were investigated against the site specific oxidation by liquid chromatography coupled to tandem mass spectrometry in a shotgun experiment. The shotgun approach detected 9350 peptides (and 2534 proteins) of which 1714 were oxidized. Eighteen peptides were found exclusively oxidized in treated platelets whereas 3 peptides were only found oxidized in control. The present data evidenced an interference with several proteins involved in platelet aggregation and platelet shape change (such as talin and vinculin).

Towards the understanding of the UV light, riboflavin and additive solution contributions to the in vitro lesions observed in Mirasol®-treated platelets.

OBJECTIVES: Pathogen reduction technologies are implemented to increase the safety of blood products. We previously showed that the UVB alone significantly contributes to the storage lesions observed in platelets treated with riboflavin/UVB using a home-made illuminator. The present study aims at confirming these observations using the commercial Mirasol® technology. METHODS: A three-arm study (untreated, UV-, Mirasol®-treated platelets) was conducted to investigate the platelet storage lesions throughout storage (n=4). A two-arm study was then designed to compare Intersol and T-PAS+ additive solutions (n=3). Phenotype and functional platelet characteristics were assessed using flow cytometry, aggregometry, antioxidant assays and metabolic parameters. RESULTS: Mirasol®-treated platelets exhibit enhanced storage lesions compared to controls (increase of activation markers and glycolysis rate, lower hypotonic shock and double-agonist activation responses, and decrease of total antioxidant capacity). Here, we also confirmed that the UV radiation alone is causing platelet lesions. Riboflavin tends to have an intracellular protective role while it decreases the extracellular antioxidant defenses. Furthermore, benefits of platelet additive solutions containing potassium and magnesium were confirmed as it reduces the extent of storage lesions. CONCLUSIONS: The photosensitizer, UV illumination and composition of the platelet additive solutions are key parameters influencing the platelet storage lesion. The clinical relevance of these findings is not fully understood and recent published clinical studies could not show increase in bleeding in patients receiving Mirasol-treated platelets. New developments in storage solutions might help to improve storage conditions of PRT-treated platelets and should be prioritised as research subject in the future.

Plasma for direct therapeutic use, for today and tomorrow: A short critical overview.

Plasma for direct therapeutic use is a fast-evolving blood component in terms of its production and presentation. More than a dozen forms are available worldwide, which is often overlooked since most countries apply policies making only one or very few forms available for treating patients in need. It is most often reserved for the same three clinical indications, i.e. overall clotting-factor deficiency, reversal of vitamin K antagonists in the context of active bleeding or prior to urgent surgery, and therapeutic plasma exchange. The level of evidence is often less robust than generally acknowledged for such major indications while novel indications are tending to emerge in medical and trauma settings. This short review explores classical views and new prospects opened up by novel presentations and statuses for therapeutic plasma.

How to mitigate the risk of inducing transfusion-associated adverse reactions.

Transfusion has become extremely safe but can still be associated with adverse reactions. Some adverse reactions can be mitigated by applying measures to donor selection, the process of separating blood components as well as hospital-based procedures consisting in matching the donor and the recipient; special attention is given to optimizing the best fit between the component and the beneficiary, which is not only an immuno-hematological challenge (fresh versus old blood, testing for certain viruses such as CMV, parvovirus B19, etc.). Considerable progress has also been achieved to strengthen the overall quality and safety of the whole transfusion chain. Guidelines and recommendations have resulted in substantial progress, and the recent revisiting of patients as part of a more holistic approach has enabled blood management programs to be created. Such programs, when wisely applied in a context of optimal blood use, reinforce patient safety; they enhance hospital recognition of transfusion and hemovigilance specialists as useful players acting in the interests of patients in full compliance with hospital budgets. This review considers the step-by-step processes that reinforce transfusion safety and identifies hurdles that cannot yet be properly addressed; it proposes steps for further progress, in light of personalized medicine.

Oxidative stress and antioxidant defenses during blood processing and storage of erythrocyte concentrates.

Oxidative lesions start accumulating in cells when the oxidant attacks overwhelm the antioxidant defenses. This review will briefly describe red blood cell storage lesions with emphasis on the consequences of oxidation and the cellular defense mechanisms, as well as the methods that can be used to monitor them. The sources of variability in red blood cell storage capacity depend on the donor characteristics, the product processing and the storage conditions. Suggestions to improve the product quality in order to ensure the best efficacy and safety for the transfused patient are also discussed.

The antioxidant capacity of erythrocyte concentrates is increased during the first week of storage and correlated with the uric acid level.

BACKGROUND AND OBJECTIVES: Red blood cells (RBCs) suffer from lesions during cold storage, depending in part on their ability to counterbalance oxidative stress by activating their antioxidant defence. The aim of this study was to monitor the antioxidant power (AOP) in erythrocyte concentrates (ECs) during cold storage. MATERIALS AND METHODS: Six ECs were prepared in saline-adenine-glucose-mannitol (SAGM) additive solution and followed during 43 days. The AOP was quantified electrochemically using disposable electrode strips and compared with results obtained from a colorimetric assay. Haematological data, data on haemolysis and the extracellular concentration of uric acid were also recorded. Additionally, a kinetic model was developed to extract quantitative kinetic data on the AOP behaviour. RESULTS: The AOP of total ECs and their extracellular samples attained a maximum after 1 week of storage prior to decaying and reaching a plateau, as shown by the electrochemical measurements. The observed trend was confirmed with a colorimetric assay. Uric acid had a major contribution to the extracellular AOP. Interestingly, the AOP and uric acid levels were linked to the sex of the donors. CONCLUSION: The marked increase in AOP during the first week of storage suggests that RBCs are impacted early by the modification of their environment. The AOP behaviour reflects the changes in metabolism activity following the adjustment of the extracellular uric acid level. Knowing the origin, interdonor variability and the effects of the AOP on the RBCs could be beneficial for the storage quality, which will have to be further studied.

The storage lesions: From past to future.

Red blood cell (RBC) concentrates are stored in additive solutions at 4oC for up to 42 days, whereas platelets concentrates (PCs) are stored at 22oC with continuous agitation for up to 5 to 7 days, according national regulations, and the use or not of pathogen inactivation procedures. Storage induces cellular lesion and alters either RBC or platelet metabolism, and is associated with protein alterations. Some age-related alterations prove reversible, while other changes are irreversible, notably following protein oxidation. It is likely that any irreversible damage affects the blood component quality and thus the transfusion efficiency. Nevertheless, there still exists a debate surrounding the impact of storage lesions, for both RBCs and PCs. Uncertainty is not completely resolved. Several studies show a tendency for poorer outcomes to occur in patients receiving older blood products; however, no clear significant association has yet been demonstrated. The present short review aims to promote a better understanding of the occurrence of storage lesions, with particular emphasis on biochemical modifications opening discussions of the future advancement of blood transfusion processes. The paper is also an advocacy for the implementation of an independent international organization in charge of planning and controlling clinical studies in transfusion medicine, in order to base transfusion medicine practices both on security principles, but also on clinical evidences.

[Not-for-profit: A report from the fourth annual symposium of ethics held by the National Institute for Blood Transfusion (France)]. / À propos du non-profit : rapport du quatrième symposium annuel d'éthique transfusionnelle de l'Institut national de la transfusion sanguine.

The not-for-profit issue has been debated in November 2016 in Paris; this issue is one of the four canonical pillars of ethical blood donation. It is intimately bound to benevolence though it is distinct, as not-for-profit calls for institutions while benevolence calls for individuals. It is indeed intended that voluntary blood donors do not benefit from their donation and are thus non-remunerated. Not-for-profit is essential since it refers to the public character of blood as a putative public resource aimed at being shared as a tribute of solidarity. A central question however is linked to the capacity- or not -of public sectors to ensure that blood components are universally available, with special mention to plasma derived drugs, without the contribution of the for profit, private sector.

Automatic washing of thawed haematopoietic progenitor cell grafts: a preclinical evaluation.

BACKGROUND AND OBJECTIVES: Autologous haematopoietic progenitor cell (HPC) is a prerequisite for high-dose chemotherapy in treatment of several haematologic and non-haematologic malignancies. HPCs are collected by apheresis and cryopreserved until infusion. Postinfusion adverse events have been in part related to the dimethyl sulphoxide (DMSO) used as cryoprotectant. The aim was to evaluate (i) an automated sequential washing procedure for DMSO removal in thawed HPC grafts and (ii) washing solutions in replacement of hydroxyethyl starch (HES)-based solutions. MATERIALS AND METHODS: A total of 26 HPC bags cryopreserved with 10% DMSO and intended for disposal were used. The Sepax-2 (Biosafe, Eysins, Switzerland) was evaluated using a sequential washing procedure. Outcomes were CD34+ cell recovery and viability after washing. RESULTS: The Ringer lactate supplemented or not with albumin 2·5-5% presented satisfactory results compared with HES solution in terms of CD34+ cell recovery and viability after washing. However, the apparition of aggregates led us to renounce to these alternative solutions. Using HES solution and a sequential washing of three bags, we showed the elimination of 95% of the DMSO, a postwash viable CD34+ cell recovery of 79·9 ± 9·4% and a total nucleated cell viability of 66·5 ± 9·3%. CONCLUSION: The preclinical evaluation of an automated sequential washing procedure for DMSO removal in thawed HPC grafts has proven to be effective and comparable to previously published data. Despite our attempt to find an alternative solution to the HES solution, more efforts should be done on this side to reach a consensus on cryopreservation protocols.

[Ethical issues in transfusion medicine]. / Dimensions éthiques en transfusion sanguine.

Ethics is on the cross road of off values that are present along the ways of transfusion medicine. This is an important tool to afford opinions as well as debates that always emerge when discussing transfusion medicine. The wording is particularly important; this was one among several others that characterized the soul of Jean-Jacques Lefrère when he opened the doors of the ethical issues of transfusion medicine.

[Blood components: Are they drugs or special medicines?]. / Les produits sanguins thérapeutiques : des médicaments ou des produits de santé à part ?

Blood transfusion and plasma derived-drugs significantly differ from other medicines in that their availability strictly depends on blood and plasma collected from healthy donors. Blood collection must comply with a double objective: to maintain donor heath safety, and to avoid any transmitted infections in recipients. This raises several ethical concerns that appear to be different from usual ethical and deontological issues linked to other pharmaceutical and industrial processes. The main concern is the non-commercialization of the human body. Words and concept are of major importance in this context. This short review aims at presenting the main issues relevant to those questions with respect to the various stakeholders.