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The article comments on the practice of spiritual bloodletting in certain European countries. Topics covered include the views of Saint Bernard of Clairvaux, author of "Sermon on the Spiritual Bloodlettings," and theologian Saint Hildegaard von Bingen on the practice, the proposal by Doctor Gottfried Hertzka as to the use of bloodletting to ease the purification of the body and the soul, and the potential harm caused by bloodletting to donors and patients.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives Many communication campaigns to encourage people to give blood rely on “save lives” messages, even though there is no experimental evidence as to the effectiveness of this kind of argument with respect to blood donation. The objective of this study is to test experimentally if it is indeed an effective way to prompt people to give blood, in order for communication campaigns to be evidenced-based. Methods One thousand and twenty-two lapsed blood donors were sent, at random, either a standard letter or the same letter containing an additional “save lives” message. The blood donation center measured intention to donate and actual donor return rate (3%) after 10 months. Results Although fewer people in the “save lives” condition said they had no intention to give blood again, the “save lives” letter did not lead to more donor returns than the standard letter. Conclusions Our results suggest that contrary to intuition, campaigns to promote blood donation should not rely blindly on “save lives” arguments. [ABSTRACT FROM AUTHOR]

Abstract: Pathogen inactivation of blood products represents a global and major paradigm shift in transfusion medicine. In the next near future, it is likely that most blood products will be inactivated by various physicochemical approaches. The concept of blood safety will be challenged as well as transfusion medicine practice, notably for donor selection or biological qualification. In this context, it seems mandatory to develop analytical economic approaches by assessing costs-benefits ratio of blood transfusion as well as to set up cohorts of patients based on hemovigilance networks allowing rigorous scientific analysis of the benefits and the risks of blood transfusion at short- and long-term. [Copyright &y& Elsevier]

We describe the case of a 30-year-old man with a severe autoimmune disease characterized by cryoglobulinaemia, pulmonary hypertension, Raynaud's phenomenon, lymphadenopathy, and glomerulonephritis. Despite initial remission following autologous stem cell transplantation, his disease relapsed and he died from pulmonary hypertension. At presentation the patient had hypergammaglobulinaemia and a number of autoantibodies, including rheumatoid factor (1:10240). The most striking feature was the extremely high level of cryoglobulins. The cryoprecipitate consisted of polyclonal IgM, IgG and albumin. Interestingly, the albumin in the cryoprecipitate was exclusively present in SS-bonded oligomeric forms, and contained an abnormal acidic component as judged by 2D gel electrophoresis. Oxidized albumin was also present in serum, and represented a small but significant fraction. None of the many known albumin variants have so far been associated with a particular disease; thus our results may represent the first description of an altered albumin associated with severe disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Abstract 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. [ABSTRACT FROM AUTHOR]

Abstract 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Résumé Une discussion autour du thème du non-profit, l’un des piliers majeurs du don (de sang) dit éthique, a fait l’objet d’un séminaire en novembre 2016 à Paris. Ce principe est intimement lié à celui du bénévolat, bien que les deux notions soient distinctes, la première s’adressant davantage aux institutions et la seconde aux individus, mais il est aussi communément entendu que les individus ne sont pas appelés à obtenir un profit de leur don, quand bien même ils seraient bénévoles puisque des formes de bénévolats rémunérés ou compensés existent. Le non-profit est une notion essentielle car il se réfère au caractère de « bien public » du sang en tant que ressource pouvant faire l’objet d’un partage solidaire ; un des questionnements les plus actuels est lié à la capacité— ou non —des secteurs exclusivement publics à assurer la couverture en produits sanguins en particulier médicamenteux (fractions dérivées du plasma) capables de répondre à tous les besoins sans qu’ils aient besoin d’avoir recours au système privé à but lucratif. 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. [ABSTRACT FROM AUTHOR]

Résumé Le volontariat est l’un des quatre grands principes éthiques du don de sang, consacré par l’usage mais pas par la législation. De plus, à l’heure du « marketing », nécessaire pour l’atteinte des objectifs non seulement quantitatifs mais aussi qualitatifs de la collecte, des messages sont adressés aux donneurs de sang qui pourraient altérer stricto sensu la notion de volontariat. Ce séminaire – partie d’une série de séminaires en éthique transfusionnelle – avait pour objectif de discuter de la notion de volontariat au don de sang et de sa fragilité, en faisant appel à d’autres expériences que le don de sang, et en invitant des spécialistes de nombreuses disciplines des sciences médicales, humaines et juridiques à en débattre. Voluntariness stands for one of the four pillars of ethics in blood donation; it is, however, more related to tradition than to legislation. Because it seems necessary to apply “marketing” techniques to blood collection in order to meet the needs in blood components, both in terms of quantity and quality, one wonders if this may be at the expense of this principle of voluntariness. This seminar–belonging actually to a series of seminars in Ethics in Transfusion Medicine–aimed at questioning the possible weakness of voluntariness in the field of blood donation. To achieve this goal, specialists of numerous disciplines in medical sciences, law and humanities gathered to discuss all related issues to voluntariness in blood donation. [ABSTRACT FROM AUTHOR]

Background and objectives Hepcidin is the main hormone that regulates iron balance. Its lowering favours digestive iron absorption in cases of iron deficiency or enhanced erythropoiesis. The careful dosage of this small peptide promises new diagnostic and therapeutic strategies. Its measurement is progressively being validated and now its clinical value must be explored in different physiological situations. Here, we evaluate hepcidin levels among premenopausal female donors with iron deficiency without anaemia. Materials and Methods In a preceding study, a 4-week oral iron treatment (80 mg/day) was administered in a randomized controlled trial ( n = 145), in cases of iron deficiency without anaemia after a blood donation. We subsequently measured hepcidin at baseline and after 4 weeks of treatment, using mass spectrometry. Results Iron supplementation had a significant effect on plasma hepcidin compared to the placebo arm at 4 weeks [+0·29 n m [95% CI: 0·18 to 0·40]). There was a significant correlation between hepcidin and ferritin at baseline ( R2 = 0·121, P < 0·001) and after treatment ( R2 = 0·436, P < 0·001). Hepcidin levels at baseline were not predictive of concentration changes for ferritin or haemoglobin. However, hepcidin levels at 4 weeks were significantly higher (0·79 n m [95% CI: 0·53 to 1·05]) among ferritin responders. Conclusions This study shows that a 4-week oral treatment of iron increased hepcidin blood concentrations in female blood donors with an initial ferritin concentration of less than 30 ng/ml. Apparently, hepcidin cannot serve as a predictor of response to iron treatment but might serve as a marker of the iron repletion needed for erythropoiesis. [ABSTRACT FROM AUTHOR]

Erythrocyte concentrates are the major labile blood products used for transfusion worldwide. Erythrocyte concentrates are stored at 4°C for up to 42-49 days in additive solutions. This storage induces cellular lesions, which include alterations in red blood cell (RBC) metabolism, protein content and rheological properties. The impact of these storage lesions is intensely debated, because transfusion-related clinical adverse outcomes have been associated with the age of erythrocyte concentrates. Although altered red blood cell metabolism and early rheological changes are reversible with one transfused, oxidized proteins cannot be repaired. Thus, some irreversible damage might affect the quality of the blood product and the efficiency of the transfusion. In vivo, red blood cells are constantly exposed to oxygen fluxes but are well equipped to deal with oxidative challenges. Moreover, erythrocytes can eliminate oxidized proteins by capturing them in microvesicles, which are subsequently shed into the medium. This review discusses some biochemical aspects of RBC storage and microvesiculation. [ABSTRACT FROM AUTHOR]

Background and Objective Restless legs syndrome ( RLS) is a frequent condition with a prevalence of 5-15% in the general population. Clinical and genetic observations have shown that iron deficiency, highly prevalent among blood donors, can be related to RLS. The objective of this study was to assess the prevalence of RLS in female blood donors 1 week after blood donation. Methods One week after blood donation, 291 female blood donors, aged <50 years, self-responded to all four RLS questions defined by the 1995 International RLS study group. Blood donation rate, fatigue, aerobic capacity, menstruation, mood disorder and quality of life were also assessed along with haemoglobin and ferritin blood concentrations. Results Prevalence of RLS in female blood donors 1 week after blood donation was 6·9% ( CI 95% 4·2-10·4%). Female blood donors with RLS had a higher prevalence of hyper-menorrhaea ( P = 0·033) and were significantly more tired ( P = 0·001). We observed no associations between RLS and number of previous donations ( P = 0·409), aerobic capacity ( P = 0·476), mood disorder ( P = 0·169), quality of life ( P = 0·356), haemoglobin ( P = 0·087), and serum ferritin level ( P = 0·446). Conclusion Restless legs syndrome prevalence in female blood donors is not as important as described in some other studies, which could reassure blood donors. The prevalence of hypermenorrhaea and fatigue is higher in RLS blood donors. Therefore, screening for fatigue and hypermenorrhaea could be considered as these symptoms are associated with RLS in female blood donors. [ABSTRACT FROM AUTHOR]

Abstract: The term “proteomics” covers tools and techniques that are used to analyze and characterize complex mixtures of proteins from various biological samples. In this short review, a typical proteomic approach, related to the study of particular and illustrative situation related to transfusion medicine is reported. This “case report” will allow the reader to be familiar with a practical proteomic approach of a real situation, and will permit to describe the tools that are usually used in proteomic labs, and, in a second part, to present various proteomic applications in transfusion medicine. [Copyright &y& Elsevier]

Pathogen reduction of platelets (PRT-PLTs) using riboflavin and ultraviolet light treatment has undergone Phase 1 and 2 studies examining efficacy and safety. This randomized controlled clinical trial (RCT) assessed the efficacy and safety of PRT-PLTs using the 1-hour corrected count increment (CCI) as the primary outcome. A noninferiority RCT was performed where patients with chemotherapy-induced thrombocytopenia (six centers) were randomly allocated to receive PRT-PLTs (Mirasol PRT, CaridianBCT Biotechnologies) or reference platelet (PLT) products. The treatment period was 28 days followed by a 28-day follow-up (safety) period. The primary outcome was the CCI determined using up to the first eight on-protocol PLT transfusions given during the treatment period. A total of 118 patients were randomly assigned (60 to PRT-PLTs; 58 to reference). Four patients per group did not require PLT transfusions leaving 110 patients in the analysis (56 PRT-PLTs; 54 reference). A total of 541 on-protocol PLT transfusions were given (303 PRT-PLTs; 238 reference). The least square mean CCI was 11,725 (standard error [SE], 1.140) for PRT-PLTs and 16,939 (SE, 1.149) for the reference group (difference, −5214; 95% confidence interval, −7542 to −2887; p < 0.0001 for a test of the null hypothesis of no difference between the two groups). The study failed to show noninferiority of PRT-PLTs based on predefined CCI criteria. PLT and red blood cell utilization in the two groups was not significantly different suggesting that the slightly lower CCIs (PRT-PLTs) did not increase blood product utilization. Safety data showed similar findings in the two groups. Further studies are required to determine if the lower CCI observed with PRT-PLTs translates into an increased risk of bleeding. [ABSTRACT FROM AUTHOR]

Background and Objectives Microparticles (MPs) are small phospholipid vesicles of less than 1 µm, shed in blood flow by various cell types. These MPs are involved in several biological processes and diseases. MPs have also been detected in blood products; however, their role in transfused patients is unknown. The purpose of this study was to characterize those MPs in blood bank conditions. Materials and Methods Qualitative and quantitative experiments using flow cytometry or proteomic techniques were performed on MPs derived from erythrocytes concentrates. In order to count MPs, they were either isolated by various centrifugation procedures or counted directly in erythrocyte concentrates. Results A 20-fold increase after 50 days of storage at 4°C was observed (from 3370 ± 1180 MPs/µl at day 5 to 64 850 ± 37 800 MPs/µl at day 50). Proteomic analysis revealed changes of protein expression comparing MPs to erythrocyte membranes. Finally, the expression of Rh blood group antigens was shown on MPs generated during erythrocyte storage. Conclusions Our work provides evidence that storage of red blood cell is associated with the generation of MPs characterized by particular proteomic profiles. These results contribute to fundamental knowledge of transfused blood products. [ABSTRACT FROM AUTHOR]