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Background Norway has no overview of the number of patients who are transfused, their age and gender distribution or reasons for transfusion. We wished to investigate which patient groups received blood at Sorlandet Hospital in 2010-2011, and to test a method of electronic data linkage from treatment systems, with a view to further monitoring of blood consumption. Material and method Data from all patients treated in somatic departments at Sorlandet Hospital in the period from 1 January 2010 to 31 December 2011 were linked to data from the blood bank with the aid of the system 'Forskning i sykehus'. SPSS version 23.0 was used for the statistical analyses. Results A total of 19 108 red blood cells and platelet concentrates were transfused to 3 967 patients, with the same number of units for both genders. Patients older than 60 years accounted for 79 % of the total blood consumption. Patients in the main diagnostic group neoplasms had the most transfusion episodes, followed by the diagnostic groups injuries, diseases of the digestive system and diseases of the blood. In cases of primary and secondary hip prostheses, 33.8 % and 65.6 % of the patients received blood, respectively. For caesarean section the figure was 8.9 %. Interpretation Our data are comparable to data from other countries. The method is suitable for assessing and monitoring transfusion practice. It could also be used by other health trusts and to collect national data after all blood components and parameters such as haemoglobin, blood group and transfusion complications are included.

Significant perioperative bleeding and transfusions of plasma, red blood cells (RBCs), and platelets are considered part of the normal clinical course of orthotopic liver transplantation (OLT).1 By far the two most common plasma products available today are fresh frozen plasma (FFP) from single blood donors and solvent/detergent (SD)-treated pooled plasma. Whereas FFP does not undergo any kind of pathogen inactivation, the SD treatment secures pathogen reduction.2–4 Due to dilution and possible neutralization of the responsible antibodies, SD-plasma has a markedly lower rate of allergic/immunologic reactions including no reported cases of transfusion related acute lung injury (TRALI) despite over 10 million units transfused.5,6 Further, SD-plasma can be regarded as a biopharmaceutical product with standardized amounts of coagulation factors as compared to FFP where there is great bag-to-bag variation.7 Accordingly, SD-plasma has gained increased popularity during the last two decades and has partly replaced FFP in Canada, Mexico, and many European countries. One disadvantage of SD-plasma is that the SD-process inevitably reduces the levels of α2-antiplasmin and protein S, and could increase the risk of hyperfibrinolysis8 or thromboembolic events such as pulmonary embolism during liver transplantation.9 In addition to the track record of SD-plasma in Europe during the last two decades, both randomized controlled trials10–12 and critical reviews4,6 have suggested that these risks are largely theoretical. US SD-plasma was first introduced in 1998, but production was terminated in 2002–2003 in part due to thromboembolic complications not observed with European SD-plasma. Quality differences between European and US SD-plasma that can be responsible for these adverse effects have since been documented.13,14 Based on newer hemovigilance data, the adverse events incidence per 10,000 units of FFP compared to SD-plasma is: 0.29 versus 0.00 for TRALI; 34.48 versus 2.92 for severe allergic reactions; 153.85 versus 10.53 for all allergic reactions. To our knowledge, no such adverse events data have been detailed for liver transplant patients, nor have incidence data been published for hyperfibrinolysis or thromboembolism.15 Recently the US Food and Drug Administration (FDA) licensed the European SD-plasma, OctaplasLG (Octapharma AG, Lachen, Switzerland), for clinical use in the United States. Taking the costs of adverse effects of plasma products into account, a recent report suggests that replacing FFP with OctaplasLG may be cost effective.16 In Norway, the SD-plasma product Octaplas has been the only plasma product transfused since 1993. A quality assurance study to investigate transfusion load and eventual side effects after liver transplantation was undertaken in the period from 2005 to 2009 to explore the consequences of using this product in the liver transplantation unit serving the whole Norwegian population of 5×106 inhabitants. Special emphasis was placed on possible hyperfibrinolysis and thromboembolism.

Antinuclear factors (ANFs) were studied in sera of 51 SLE probands, 615 relatives and their 313 spouses who served as controls. The frequency of ANFs in the relatives was correlated to certain variables present in the SLE probands: i: A very marked accumulation of speckled ANF was found in relatives of SLE probands with marked arthritis, whose female relatives above forty years of age more frequently had a present of past history of effusions in large joints than female relatives of SLE probands without arthritis. The frequency of ANFs in relatives was also correlated with ii: the titer of ANFs in the proband and with iii: the presence of numerous LE cells at the time of diagnosis of SLE in the proband. Selection of subroups of SLE probands with defined clinical and/or serological characteristics appears to be valuable in family studies of SLE.

The distribution of antinuclear factors in sera of 615 relatives, and their 313 spouses, of 72 SLE probands is presented. A statistically significant, but irregular, aggregation of ANFs occurred in relatives. When the different patterns of nuclear fluorescence were analysed, the homogeneous type, but not the speckled type of ANF separated the relatives and the spouses. The correlation between ANFs and rheumatic disease was more manifest for relatives than for spouses. Non-rheumatic relatives and spouses did not differ with regard to any type of ANF.

Three-hundred-and-ninety-five candidates registered for a first cadaveric renal transplant have been analyzed for the effect of pre-graft blood transfusions. Of these, 348 patients were transplanted, 45 died prior to transplantation and two patients have not yet received a transplant. Slightly less than half of the transplanted patients had been transfused, and those receiving five or more transfusions demonstrated a superior graft survival. This was pronounced in all HLA incompatible transplants who had received five or more transfusions. In patients who received less than five transfusions, only one-two HLA antigen incompatible transplants demonstrated increased graft survival. The frequency of rejection episodes was significantly decreased in all transfused compared to non-transfused groups. Among the patients dying while waiting for a transplant, the majority had been transfused, and a significantly higher proportion of them had cytotoxic HLA antibodies, compared to those who were transplanted.

The outcome of 461 prospectively HLA-A, -B and -C typed and 193 prospectively HLA-DR typed cadaveric kidney transplants in one center was followed. We found a significant beneficial effect on graft survival both of HLA-A and -B as well as of HLA-DR matching between donor and recipient, while no effects of HLA-C compatibility could be detected. The effect of HLA-DR matching was clearly more pronounced than that of HLA-A and -B matching, and a possible influence of matching for HLA-A and -B could only be seen in the HLA-DR mismatched combinations. Pretransplant blood transfusions were associated with an increased graft survival only in patients receiving HLA-DR mismatched transplants. We conclude that major emphasis should be laid on obtaining HLA-DR compatibility in clinical renal transplantation.

Five antisera raised within HLA-A and -B compatible, HLA-D disparate combinations were reactive in a modified NIH microcytotoxicity test with B lymphocytes, but not with T lymphocytes from the immunizing donor, as well as with B lymphocytes from most or all donors sharing his immunizing HLA-D phenotype. Four antisera recognized structures closely associated with the HLA-D determinants Dw2, Dw3, Dw4 and LD 108. One serum had a broad reactivity pattern including Dw3, Dw6 and some unknown specificity(ies). In population and family studies, these B lymphocyte antigens behaved as if they were governed by one genetic locus in the B-D region of the HLA complex. We conclude that the antisera produced by this method recognize Ia-like antigens identical to or very closely associated with the HLA-D determinants.

Thanks to many blood safety interventions introduced in developed countries the risk of transfusion transmitted infections has become exceedingly small in these countries. However, emerging pathogens still represent a serious challenge, as demonstrated by West Nile virus in the US and more recently by Chikungunya virus in the Indian Ocean. In addition bacterial contamination, particularly in platelets, and protozoa transmitted by blood components still represent sizeable risks in developed countries. In developing countries the risk of all transfusion transmitted infections is still high due to insufficient funding and organisation of the health service. Pathogen reduction of pooled plasma products has virtually eliminated the risk of transfusion transmitted infections, without compromising the quality of the products significantly. Pathogen reduction of blood components has been much more challenging. Solvent detergent treatment which has been so successfully applied for plasma products dissolves cell membranes, and can, therefore, only be applied for plasma and not for cellular blood components. Targeting of nucleic acids has been another method for pathogen inactivation of plasma and the only approach possible for cellular blood products. As documented in more than 15 year's track record, solvent detergent treatment of pooled plasma can yield high quality plasma. The increased risk for contamination by unknown viruses due to pooling is out weighed by elimination of TRALI, significant reduction in allergic reactions and standardisation of the product. Recently, a promising method for solvent detergent treatment of single donor plasma units has been published. Methylene blue light treatment of single donor plasma units has a similar long track record as pooled solvent detergent treated plasma; but the method is less well documented and affects coagulation factor activity more. Psoralen light treated plasma has only recently been introduced (CE marked in Europe, but not licensed by the FDA), while the method of Riboflavin light treatment of plasma still is under development. In addition to pathogen reduction the methods, however, result in some reduction of coagulation factor activity. For platelets only Psoralen and Riboflavin light treatment have been implemented. Both are CE marked products in Europe but only approved for clinical trials in the USA. The methods affect platelet activity, but result in clinically acceptable platelets with only slightly reduced CCI and increased demand for platelet transfusions. Pathogen reduction of red blood cells with FRALE (S-303) or INACTINE (PEN110) has so far resulted in the formation of antibodies against neo-epitopes on red blood cells. A promising method for Riboflavin treatment of red blood cells is under development. This manuscript reviews the current experience and discusses future trends.

Background and Objectives Therapeutic or prophylactic use of platelet concentrates (PC) is essential for patients with thrombocytopenia due to intensive chemotherapy for various malignancies. PC quality has been improved after introduction of storage containers that are more oxygen permeable than the second-generation PC containers. Consequently, shelf life of PCs at our blood bank has been extended to 6·5 days after monitoring each PC for bacterial contamination. In this prospective observational study, we compared apheresis PCs harvested by Amicus cell separator with buffy-coat (BC) PCs during storage for up to 6·5 days. Materials and Methods All PCs were collected from healthy volunteer donors and were prepared for routine clinical use. A total of 446 transfusion episodes with 688 PCs for 77 adult patients with oncological and haematological diseases were registered during a 13-month period. Outcome measures were corrected count increment after 1 h (CCI-1), after 18–24 h (CCI-2), and transfusion intervals. Transfusions were carried out after storage from 1·5 to 6·5 days. Results Both CCI and the transfusion intervals decreased statistically significantly by increasing storage time after transfusions with apheresis PCs or BC PCs. However, less than 4% of the variation in CCI and transfusion interval could be explained by platelet storage time. There were no significant differences between BC PCs and apheresis PCs, regarding CCI and transfusion intervals. Conclusion We can conclude that BC PCs are not inferior to apheresis PCs, and may serve the clinical purposes as well as apheresis PCs harvested by Amicus.

ABO-incompatible transfusions and transfusion-related lung injury are today the leading transfusion-related causes of death in the developed world. Since anti-A and anti-B antibodies in plasma can give rise to serious, even fatal, transfusion reactions, ABO-identical/compatible plasma is indicated, but presents a logistical challenge and a risk for transfusion of incorrect plasma. In an effort to circumvent these problems, an ABO-independent universally applicable, pathogen-reduced plasma, Uniplas, has been developed and proven safe and efficacious for use in adults through prospective, randomized, controlled open-heart surgery studies and in prospective, parallel group, controlled liver resection studies. The results of these trials are presented and discussed in relation to solvent/detergent (SD) treated plasma, in general. The cost effectiveness of pathogen-reduced plasma is low because of the very low risk for transfusion transmitted viral infections in the developed world (US 2 to 9 million dollars per quality-adjusted life year). However, taking into account the combined safety of Uniplas with regard to transfusion-related lung injury, pathogen reduction and independence of ABO blood groups, the cost per gained life year is reduced to US 40,000 dollars to 100,000 dollars.

Background and Objectives The compatibility of an ABO blood group independently applicable plasma, Uniplas, was explored in liver resection because patients undergoing liver resection frequently require the transfusion of plasma to compensate for blood loss and/or clotting factors. Materials and Methods One-hundred and twenty two patients undergoing elective liver resection were enrolled; 81 patients required plasma transfusion, while 41 did not. Of those in need of plasma, 58 were blood group A, B or AB, and 23 were blood group O. Patients were monitored up to day 7 postoperatively for signs of haemolysis and haemostasis, and viral markers were assessed at baseline and 3 weeks postoperatively. Results Uniplas transfusions of up to 50·7 ml/kg body weight were given per treatment episode, without signs of haemolysis caused by transfusion. A total of 94/99 patients (95%) were negative in the direct antiglobulin test throughout the study. Two patients, one transfused with Uniplas, the other not, had a positive direct antiglobulin test result at baseline, while three of 64 patients transfused with Uniplas demonstrated a change from having negative to intermittently positive direct antiglobulin test results without concurrent signs of haemolysis. International normalized ratio, activated partial thromboplastin time and protein C levels were maintained by transfusion of plasma (≥ 20 ml/kg body weight). No patient underwent seroconversion for human immunodeficiency virus, hepatitis B virus or hepatitis C virus. Positivity for hepatitis A virus (HAV) immunoglobulin G (IgG) in 11 patients from the Uniplas group (who tested HAV immunoglobulin M negative), together with an apparent seroconversion for parvovirus B19 seen in two patients who received Uniplas, indicated passively transferred IgG antibodies. Conclusions No haemolysis was observed as a result of Uniplas transfusions up to 50·7 ml/kg body weight per treatment episode in patients undergoing liver resection. Moreover, transfusion (≥ 20 ml/kg body weight of Uniplas) maintained acceptable levels of international normalized ratio, activated partial thromboplastin time and protein C.

Both red blood cells and platelets undergo lesions upon storage which affect their function and possibly their clinical outcome. Some of these lesions are reversible, others not. Improved additive solutions and leukocyte depletion can delay the appearance of storage lesions. In addition, cellular apoptosis leads to numerous mitochondrial and surface changes during storage which have the potential to induce immune suppression by tuning down the innate immune system. This overview highlights some laboratory and clinical aspects of red cell and platelet storage lesions.

Microchimerism may play a part in transfusion complications. The aim of this study was to examine whether establishment of post-transfusion microchimerism was related to leukocyte content.Twenty non-pregnant female patients, without known malignant or immunological diseases, mean age 68 years, receiving 2-4 units of red blood cell concentrates during elective surgery, were included. One or two of the units were from male donors. Ten patients received buffy-coat depleted red blood cell concentrates, leukocyte count 108-109 per unit, and 10 patients received red blood cells leukoreduced by prestorage leukocyte filtration, with a leukocyte count of106 per unit. EDTA samples were collected in vacuum tubes before and after 1 week and 6 months after transfusion. The tubes were frozen and stored at -400 degrees C. Genomic DNA was isolated and PCR performed using four primer sets amplifying markers on the Y-chromosome.Microchimerism was detected in a total of eight out of the 20 patients. In three patients microchimerism was detected only before transfusion. These patients had given birth to one or two boys each, and had no history of previous transfusion. Two patients receiving buffy-coat depleted red blood cell concentrates and two patients receiving leukoreduced red blood cell concentrates had detectable microchimerism 1 week after transfusion. The age of the transfused red blood cell concentrates was 6, 24, 8 and 7 days, respectively. One patient receiving leukoreduced red blood cell concentrates had detectable microchimerism after 6 months. The age of this concentrate was 22 days.This study demonstrates that microchimerism after transfusion does not seem to be dose dependent, and can be induced even by a3 week old leukoreduced red blood cell concentrate with a very low leukocyte content.

Plasma and red blood cell quality are affected both by citrate concentration and the levels of extracellular leukocyte and platelet derived substances, accumulated during storage of blood. The effect of leukocyte filtration on the storage stability of whole blood was therefore studied in blood collected in standard CPD and 0.5CPD (CPD with half strength citrate concentration). A total of 52 units, 12 of them with reduced citrate concentration, were leukocyte-filtered with Pall( whole blood filter (WBF1 or 3). No differences in leukocyte or platelet reduction were observed with the two citrate concentrations. However, with 0.5CPD a significantly longer filtration time and increased complement activation was observed. The effect of pre-storage leukocyte filtration on the plasma quality of whole blood was therefore only studied with standard CPDA1 anticoagulant solution (normal strength citrate concentration). Leukocyte filtration did not affect the von Willebrand factor concentration, while a small reduction (7%, p=0.04) in factor VIII (FVIII) concentration was observed. During storage, however, FVIII decreased more slowly in the filtered than in the unfiltered product, and, from day two, the FVIII content was significantly higher in the filtered product (46% versus 30% at 28 days, p0.001). Factor V (FV) demonstrated a 16% reduction (p0.001) upon filtration, followed by an additional 8% in the next 24 h and only a 4% reduction the next 27 days, while unfiltered products demonstrated a continuous reduction to 26% at 28 days. While the beta-thromboglobulin (beta-TG) concentration significantly increased (from 836 to 2483 IU/ml, p0.001) during leukocyte filtration, no further increase was observed during storage. In contrast, unfiltered products demonstrated an increase to 5762 IU/ml (p0.001) at 14 days, followed by a slight, not significant, reduction. This indicates platelet activation during filtration and explains a parallel reduction in FV. Filtration induced no increase in prothrombin fragment 1+2, while a slight increase was observed in some unfiltered products after 28 days of storage.Pre-storage leukocyte depletion thus improves the coagulation factor content of plasma in stored whole blood.

The establishment of the Norwegian Fractionation Project (Project) was of major importance in preserving national self-sufficiency when plasma, cryoprecipitate and small batch factor IX-concentrates were replaced by virus inactivated products in the last part of the 1980s. Fractionation was performed abroad by contract with Octapharma after tenders on the European market. All Norwegian blood banks (>50) participated in the Project. Total yearly production was 50–60 tons of mainly recovered plasma. From 1993 solvent detergent (SD) treated plasma has replaced other plasma for transfusion. The blood banks paid for the fractionation and/or viral inactivation process, while the plasma remained the property of the blood banks and the final products were returned to the blood banks. The Project sold surplus products to other Norwegian blood banks and the majority of the coagulation factor concentrates to The Institute of Haemophilia and Rikshospitalet University Hospital. Both plasma and blood bank quality was improved by the Project. Clinical experience with the products has been satisfactory and self-sufficiency has been achieved for all major plasma proteins and SD plasma, but a surplus exceeding 3 years consumption of albumin has accumulated due to decreasing clinical use. The Project has secured high yields of the fractionated products and the net income from the produced products is NOK 1115 (140 € or US$) per litre plasma. An increasing surplus of albumin and the possibility of significant sales abroad of currently not fractionated IVIgG, could lead to a reorganisation of the Project from that of a co-ordinator to a national plasma handling unit. This unit could buy the plasma from the blood banks and have the plasma fractionated by contract after tender, before selling the products back for cost recovery. The small blood banks could produce plasma for products for the Norwegian market, while surplus products from the larger blood banks which are certified for delivery of plasma for fractionation of products to be consumed in the European Community, could be sold on the international market.

Blood product transfusions can be life saving and must be considered in the supportive care of children of any age with underlying oncological or haematological problems, as well as after major surgery or after serious trauma. Paediatric transfusions are particularly challenging because life-long effects of transfusion complications are more durable and serious in children than in adults, in whom the median age at transfusion is >70 years (Tynell E, Norda R, Shanwell A, Bjorkman A. Long-term survival in transfusion recipients in Sweden, 1993. Transfusion 2001, 41, 251–255). While the general indications for transfusions in paediatric patients are similar to adults, the threshold, volumes and infusion rates for transfusions vary with age. In this Update, we discuss current blood products, then suggest transfusion ‘triggers’ in major surgery and haematological and oncologic practice. Finally, future developments and new possibilities are considered.

Background and objectives: Delay between blood collection and the separation of its components may result in lowered yield of factor VIII (FVIII) and loss of 2,3-biphosphoglycerate (2,3-BPG). This study was to see whether the use of 0.5 CPD resulted in better preservation of FVIII and maintenance of 2,3-BPG. Materials and methods: 55 units of blood were collected in 0.5CPD and 48 in CPD SAG-M. Ten of the collections were paired, so that the same donors were bled in a single session partly in an 0.5CPD system and partly in CPD SAG-M. After collection, the blood was promptly cooled to 20 °C and stored at that temperature for up to 24 h. Results: Preservation of FVIII activity was significantly better in 0.5CPD compared with CPD. The content of von Willebrand factor was stable in the anticoagulant solutions for 24 h at that temperature. Plasma separated from both media had low levels of prothrombin fragment 1+ 2 and complement activation. Paired collections substantiated previous reports that red cell storage is significantly improved in 0.5CPD compared with CPD SAG-M with respect to 2,3-BPG and haemolysis. Conclusions: Red cell metabolism and oxygen-releasing capacity are kept at acceptable levels in 0.5CPD blood for 24 h at 20 °C before component separation. The concentration of red cell 2,3-BPG remained at normal or slightly subnormal levels during further storage in 0.5CPD at 4 °C for 2–4 weeks before gradual decay to an average of 39% at 48 days.

Most parous women have progenitor cells of offspring origin in their peripheral blood for various time periods after giving birth [1,2]. Artlett and colleagues have shown a rate of microchimerism in parous women of 28% [3]. Postpartum women may be microchimeric to offspring hematopoietic cells up to 27 years [1]. However, little is known about the effects of microchimerism in a normal person, but the appearance and persistence of allogeneic white blood cells in a recipient after transplantation, transfusion, or pregnancy has the potential for far-reaching biologic ramification [4]. Microchimerism and HLA-relationships of host and non-host cells may be involved in autoimmune disease [2]. On the other hand, it has been suggested that cellular microchimerism is a physiologic phenomenon in parous women [5]. Starzl et al. described the development of tolerance in five patients who received kidney allografts

In a pilot phase I/II study we have tested synthetic ras peptides used as a cancer vaccine in 5 patients with advanced pancreatic carcinoma. The treatment principle used was based on loading professional antigen-presenting cells (APCs) from peripheral blood with a synthetic ras peptide corresponding to the ras mutation found in tumour tissue from the patient. Peptide loading was performed ex vivo and the next day APCs were re-injected into the patients after washing to remove unbound peptide. Patients were vaccinated in the first and second week and thereafter every 4-6 weeks. In 2 of the 5 patients treated, an immune response against the immunising ras peptide could be induced. None of the patients showed evidence of a T-cell response against any of the ras peptides before vaccination. The treatment was well tolerated and could be repeated multiple times in the same patient. Side effects were not observed even if an immunological response against the ras peptide was evident. We conclude that ras peptide vaccination according to the present protocol is safe and may result in a potentially beneficial immune response even in patients with advanced malignant disease.

The solvent/detergent (SD) process used for plasma can safely inactivate all lipid-enveloped viruses. The introduction of a specific prion-binding ligand gel in combination with SD treatment, time-reduced from 4 to 1-1.5 h, still ensures efficient virus kill, reduces abnormal prion protein by >5 log steps, and preserves levels of plasmin inhibitor at close to the reference range. Infections with known non-enveloped viruses such as HAV or parvovirus B19 are prevented by ensuring low virus loads in the starting plasma units, dilution through pooling of single plasma units, and neutralization of immune antibodies already present in the initial plasma pools. The major advantages of SD plasma over fresh frozen plasma and the other pathogen-inactivated plasmas are its extreme safety with respect to transfusion-related acute lung injury and the significantly lower likelihood of provoking allergic reactions. Both advantages are best interpreted as results of the dilution effect of pooling. No fewer than 18 clinical studies covering all indications for plasma, and extensive clinical experience have shown that reduced levels of coagulation factors and inhibitors as a result of SD treatment do not impair significantly the clinical efficacy or tolerance of plasma. Properly standardized clotting factor and inhibitor potencies and low batch-to-batch variations when compared with single-donor plasma units makes SD plasma more suitable for standardized treatment.

Purpose of review Donor selection and viral screening methods combined with pathogen reduction have increased the safety of pooled plasma to a level which makes reintroduction of ABO-universal plasma an important option. Recent findings Solvent detergent-treated pooled plasma has proved to be well suited for the production of pathogen-reduced ABO-universal plasma. One such product, Bioplasma FDP, was licensed in South Africa in 1994 and has since 1996 been in successful clinical use. A clinical study with this product and two studies with the European product, Uniplas, have confirmed the efficacy and safety of pathogen-reduced ABO-universal plasma. Summary Pooling of plasma enables the production of ABO-universal plasma. Pathogen reduction with solvent detergent eliminates lipid-enveloped viruses, whereas neutralizing antibodies in the plasma pool and nucleic acid amplification testing ensures the safety for recognized nonlipid-enveloped viruses. Pooling also eliminates transfusion-associated acute lung injury (the leading cause of plasma transfusion-related death), reduces immunologic/allergic adverse events by 60-80% and standardizes plasma protein content. Thus, in addition to ABO compatibility, pathogen-reduced ABO-universal plasma has important supplementary benefits that improve the product's cost-effectiveness.

This report summarizes the need for changes in certain areas of transfusion practice that may have some beneficial effect in improving transfusion safety and reducing the ever increasing demand for the use of red blood cells. These dual objectives can be achieved through a continuous educational and quality awareness program, encouraging the use of other available alternatives, including implementation of transfusion triggers reducing hemoglobin values, increased application of peri-operative/post-operative blood salvage, introduction of improved additive solutions and apheresis double dose RBC with a standardized hemoglobin content per unit; and changes in the clinical/laboratory practices, in particular when preparing patients for surgery. It is only through continuous education integration of better diagnosis/development/research and clinical practices in targeted patients that one can anticipate making a true contribution to the plodding and controversial issue of predicting transfusion safety and the cost benefit value of alternative strategies for transfusion. The current opinions on "safer transfusion" through the use of currently available alternatives are highlighted with the goal of promoting the use of transfusion alternatives in everyday clinical practice.

In the present study two patients were studied in detail to estimate the quantity of IgG of donor lymphocyte origin. Using IgG subclass quantitation and Gm haemagglutination inhibition titre, we estimated that up to 3% of IgG found after transplantation may be of donor lymphocyte origin. Analysis of viral antibody patterns by imprint immunofixation suggested polyclonal production of donor-derived antibodies.

HLA antibodies are the most important cause for immunological refractorines to platelet transfusions, and their formation can be avoided in the majority of patients by exclusive use of leukocyte filtered blood products with a residual white cell count 6 per unit. Chemotherapy reduces the risk of platelet antibody formation; patients under cytostatic treatment for malignancies often demonstrate transient immunization and they can also lose antibodies present at start of the treatment. In the management of patients with immunologic refractoriness, treatment should first be attempted with HLA compatible platelets from single donors. If a transfusion effect is not obtained, cross match (lymphocytotoxicity test + platelet radioactive antiglobulin test) negative platelets from single donors should be attempted. As the next step related donors can be evaluated, and finally treatment with plasma apheresis or high dose intravenous IgG therapy should be considered.

Institute of Immunology Rikshospitalet-Radiumhospitalet Medical Centre University of Oslo 0027 Oslo, Norway e-mail: bjagees@online.no Tel.: +47 2250 6078 Fax: +47 2307 3510 duction of TRALI by HLA class-II antibodies are discussed, and it is pointed out that monocytes express the antigens, while neurophils and endothelial cells first demonstrate the antigens after activation. Thus, both antibody-activated monocytes and non-immune activating mechanisms could induce HLA class-II expression on neutrophils and endothelial cells. Dr. Wallis has observed TRALI with a frequency of 1 in 7900 units of FFP transfused and a high rate of fatality. He points out that the incidence of TRALI is underestimated because complex and milder cases are easily missed, and refers to a prospective trial which demonstrated that 1 in 50 units of FFP caused some cardiorespiratory impairment. He also points out the strong relationship between ARDS and blood transfusion. Taken together with the above-mentioned prospective trial, he suggests that milder unrecognized forms of TRALI may be much more frequent than previously appreciated. Based on haemovigilance data from Scandinavia and the UK, Dr. Flesland demonstrates that TRALI is observed most frequently after transfusion of FFP, followed by red blood cells and platelets, however not after solvent detergent-treated (SD) FFP (Octaplas). He also observes strikingly lower rates of “allergic” (febrile, urticarial and anaphylactoid) reactions after transfusion of SD FFP than after transfusion of red blood cells and platelets. These reactions are not life-threatening, but most unpleasant for the patient, and labour-consuming. They are caused by antigens, antibodies and cytokines in plasma, which are substances that either are diluted or neutralized by pooling in the production process of SD FFP. The fact that no definite cases of TRALI have been reported after transfusion of many million units of SD FFP can best be explained by: • Pooling, which results in dilution and neutralization of leukocyte antibodies; • removal of cells/cell fragments together with solvent detergent treatment which reduces the amount of Intensive Care Med (2007) 33[Suppl 1]:S1–S2 DOI 10.1007/s00134-007-2872-4

Human plasma for therapeutic use, besides having optimal viral safety, must contain optimal levels of all coagulation factors and protease inhibitors to be clinically effective. Several new technologies for pathogen reduction of plasma (PRT) exist and are entering the stage of clinical testing. The main objective of this overview is to provide an update on the current states of three promising photoactive technologies that target pathogen nucleic acid for pathogen inactivation, applicable to single unit fresh-frozen plasma (FFP) and to highlight the experiences gained with classical pathogen reduction of pooled plasma using solvent-detergent (SD) treatment. It should be emphasized that none of the currently applied methods inactivate all types of pathogens and all have some effect on plasma quality when compared to fresh-frozen plasma. Pooled SD-plasma is the best documented clinical product, followed by methylene blue light treated (MBLT)-plasma. Recently, Psoralen light treated (PLT)-plasma has been introduced (CE-marked product in Europe) while Riboflavin light treated (RLT)-plasma is still under development. In principal, PRT for plasma not only differs in terms of the spectrum and log of pathogen reduction potential, but also in respect to the physicochemical/biological characteristics, and profiles of the adverse reactions, particularly in vulnerable patient groups. Therefore, an additional practical step such as oil extraction followed by chromatography to remove the solvent/detergent, and filtration or the use of some special absorbing matrix is required to reduce the residual photosensitive chemicals, their metabolites and photo adducts. This is required to improve the safety margin of the final product. Moreover, while it may be convenient to think that a combined pathogen reduction technology could improve the spectrum of known pathogens to be inactivated, one needs, in practice, to balance between the degree of pathogen reduction and the loss of some plasma protein activity. From the quality point of view, SD-plasma is a pooled standardized pharmaceutical product with extensive in-process control. However, both differences in production processes and the plasma source can influence final product quality. On the other hand, single unit plasma derived from nucleic acid PRT cannot be monitored by pharmaceutical process control and demonstrates the wide range of concentrations normally observed for plasma proteins. Pooling has the disadvantage that one single plasma unit can contaminate a whole pool, but this can be offset by several advantages that pooling and the SD process offer. Among these are reduction of a possible pathogen load by dilution and by neutralizing antibodies in the plasma pool, dilution and possible neutralization of antibodies and allergens which essentially eliminates transfusion-related acute lung injury (TRALI) and reduces allergic reactions significantly, removal of residual blood cells, cell fragments and bacteria, and removal of the largest von Willebrand-factor (vWF) molecules. On the other hand, some streamlining is required for technologies using single units of plasma, such as the use of plasma from male non-transfused donors to reduce TRALI and to avoid the O blood group in order to meet current specifications for FFP [Seghatchian J. What is happening? Are the current acceptance criteria for therapeutic plasma adequate? Transfus Apheresis Sci 2004; 31:67-79], and to exploit the potential benefit to inactivate residual lymphocytes and prevent transfusion-associated graft versus host disease. The cost effectiveness of pathogen inactivation is very low (> 2 million US dollar/life year saved), if however, non-infectious complications such as TRALI are taken into account; the cost for SDP is reduced to < 50,000 British pound/life year saved for those 48 years. Finally, from the therapeutic standpoint, two important questions still remain to be answered. First, whether the various pathogen reduced plasma products are clinically interchangeable and second, whether the conventional quality requirements of FFP are still adequate for the newer plasma products. These questions can only be answered by a head to head comparison, followed by large-scale clinical trials.

Background . Transferrin receptor mediates cellular uptake of iron, and the expression on cells reflects iron needs and erythropoietic activity. The results of measuring transferrin receptor in serum (sTfR) in blood donors are presented. Study design and methods . Haemoglobin, serum-ferritin and sTfR were measured in 172 female and 174 male donors that had donated whole blood six or more times during the previous 3 years and in 96 female and 56 male new donors. Results . Haemoglobin and sTfR were not significant different in new and repeat donors. New donors had significantly higher s-ferritin than repeat donors. Twenty donors had a Hb above the low limit for normal, but below the determined cut-off for donation. Only three of these had high sTfR and/or low serum-ferritin. Hence, of the total 492 donors 3.5% were below the Hb cut-off, but having Hb, s-ferritin and sTfR within normal ranges. 11.6% of new female donors belonged in this category. Conclusion . STfR is better than s-ferritin as a screening for iron deficiency. Most donors with low tissue iron neither have high sTfR, nor anaemia. There is probably no need to have a separate, higher than the lower normal range, requirement for Hb in donors. STfR measurements are probably most valuable in a setting where most donors are repeat donors.

A total of 61 consecutive adult patients with haematological malignancies with an HLA-identical or one antigen-mismatched haploidentical family donor were randomised to allogeneic transplantation with blood stem cells (BSC) or bone marrow (BM). The median observation time was 5 years. Apart from engraftment parameters and acute graft-versus-host disease (GVHD), transplant-related mortality (TRM), incidence and severity of chronic GVHD, relapse, leukaemia-free survival (LFS) and overall survival (OS) were recorded. In the BSC and BM group, respectively, TRM was 8/30 and 4/30 (P=0.405), the incidence of chronic GVHD was 15/26 and 11/30 (P=0.138), extensive chronic GVHD was 10/26 and 4/30 (P=0.034), and relapse one and 10 patients (P=0.007). In log-rank test restricted to the cases allografted from HLA-identical donors, the difference remained significant with regard to relapse incidence (P=0.039), but not extensive chronic GVHD (P=0.072). No difference in LFS and OS was observed. In conclusion, our study strongly indicates an enhanced graft-versus-leukaemia effect in BSC recipients, which is not expressed in increased survival. The increased chronic GVHD in these patients may contribute, but the relation is complex and not yet understood.

After solid organ transplantation donor lymphocytes have been shown to survive and multiply in the organ recipient for a prolonged period. It is not clear whether this chimerism detected is the result of immunosuppression or the cause of allograft acceptance. The number of cells transferred, as well as the type of cells, and the degree of activation are likely to be of importance for the establishment of microchimerism. The cells that are flushed out of the vascular tree may be of particular importance since when an antigen primarily bypasses or secondarily avoids organised lymphoid collections, the immune system in the recipient may remain or become "indifferent" to its presence. In the present study we examined the amount of residual donor blood cells that we could flush out from the vascular tree of living donor kidneys and cadaveric donor kidneys immediately prior to transplantation, with special emphasis on T and B lymphocytes. Our study shows that perfusion of donor kidneys just prior to transplantation releases from 0.1 to 1.8×10 6 B-lymphocytes, with an average of 0.7×10 6 and from 0.5×10 6 to 2.6×10 6 T-lymphocytes, with an average of 1.8×10 6 , for CD kidneys, and somewhat less for LD kidneys. These cells would otherwise have been flushed out into the organ recipient's circulation, where they might play a role in the establishment of microchimerism.