Production Of Blood Components Research Articles

A Case of Adult Acute Myeloid Leukemia Presenting with Musculoskeletal Manifestations

Leukemia is a heterogenous group of neoplasms that arise from the malignant transformation of hematopoietic cells. The usual presentation is one of lethargy, pallor, fever, purpura, bleeding, etc, and all this is secondary to a decrease in the production of normal blood components. However, leukemia often manifests with musculoskeletal symptoms without a systemic presentation. Musculoskeletal symptoms that precede the recognition of leukemia are much less frequent in adults as compared to those in children, and this causes diagnostic confusion and a delayed diagnosis. We describe here a case of adult acute myeloid leukemia in which pain and weakness of the limbs were the main manifestations and these were suspected as being symptoms of musculoskeletal disease.

HLA Class I and HLA Class II Antibodies in Whole Blood Donors and a Lookback on Recipients of Their Blood Components.

Introduction: Transfusion-related acute lung injury (TRALI) in recent years has become the leading cause of transfusion associated mortality. All transfusable blood components (and rarely IVIG) have been implicated in TRALI. However, plasma and single donor platelet products amount for the majority of cases. (Blood Products Advisory Committee 89th Meeting - April 27, 2007) Although the mechanism of pathogenesis is not fully known, 45 % to 60% of cases are reported to be associated with Neutrophil-Specific Antibodies (NSA) found in the donor. Less commonly, antibodies to HLA Class I and HLA Class II antigens have been implicated. Pregnancy is known to result in development of Leucocyte antibodies and HLA antibodies. (Transfusion 1999; 39:103–6) For this reason, screening of blood donors for HLA antibodies and reduced use of female donors for the production of blood components containing large plasma volumes and the exclusion of multiparous women are options to prevent TRALI. (Vox Sang 2006; 91 (Suppl 3):227)Material and Methods: At our institution, a three month (May to July 2008) retrospective review was conducted on all whole blood donors screened by the ELISA test (DONORSCREEN-HLA Class I and Class II by GTI Diagnostics @ Waukesha, WI) performed on the Quick Biotest machine. The OD for the donors as well as the cut offs were reviewed for each run. A total number of 4056 whole blood donations collected at our blood center were tested for HLA Class I and HLA Class II antibodies by this method. The Whole Blood Donors met the criteria established by AABB and FDA standards. A look back was conducted on the final disposition of the components prepared from the donors that tested positive for either HLA Class I or HLA Class II antibodies or both HLA Class I and HLA Class II antibodies. We relied on existing reporting systems in place in our institution for reporting of transfusion reaction.Results: Of the 4056 whole blood donors there were tested, 231 (5.84%) donors of which 231 (97.47%) females and 6 (2.53%) males tested positive for HLA Class I antibodies and 198 (4.93%) donors tested positive for HLA Class II antibodies of which 186 (93.94%) were females and 14 (7.07%) were males. A total number of 52 (1.28%) donors tested positive for both HLA Class I and HLA Class II antibodies of which 51 (1.26%) were females and only 1 (0.02%) was male. From the HLA Class I positive donors, 217 packed RBCs, 176 platelets and 14 plasma components were transfused. From the HLA Class II positive donors, 183 packed RBCs, 153 platelets and 11 plasma components were transfused. All of the components were irradiated. The packed RBCs and plasma were transfused via Fenwal Sepacell Leukocyte Reduction Filters. The platelets were pooled and transfused via Fenwal Sepacell PLS-10A Leukocyte Reduction Y Administration Set. The platelets were issued for transfusion within two days of donation in most instances. The patients who received plasma from the HLA positive donors did not receive IVIG treatment. The plasma that was processed from these whole blood donors that tested positive for either HLA Class I or HLA Class II antibodies were pooled with other plasma products from other whole blood donors. There were no transfusion reactions attributable to TRALI that were reported in any of the patients that received packed RBCs, platelets or plasma from these donors. There were 48 transfusion reactions reported for the same period of time that this review was conducted. All of the reported transfusion reactions were also reviewed. There were no reported cases of transfusion reactions or clinical symptoms attributable to TRALI in any of the patients that received components processed from these donors or in the patients that had reported transfusion reactions. The patients at our institution may not reflect the general patient population of other institutions, as most of our patients are immunosuppressed. This retrospective review was conducted to correlate the reported transfusion reactions with components that were transfused from HLA immunized donors. The presence of antibodies to HLA Class I or HLA Class II may not reflect the incidence of TRALI in cancer patients.

Use of statistical process control in the production of blood components

Introduction of statistical process control in the setting of a small blood centre was tested, both on the regular red blood cell production and specifically to test if a difference was seen in the quality of the platelets produced, when a change was made from a relatively large inexperienced occasional component manufacturing staff to an experienced regular manufacturing staff. Production of blood products is a semi-automated process in which the manual steps may be difficult to control. This study was performed in an ongoing effort to improve the control and optimize the quality of the blood components produced and gives an example of how to meet EU legislative requirements in a small-scale production centre. Data included quality control measurements in 363 units of red blood cells, 79 units of platelets produced by an occasional staff with 11 technologists and 79 units of platelets produced by an experienced staff with four technologists. We applied statistical process control to examine if time series of quality control values were in statistical control. Leucocyte count in red blood cells was out of statistical control. Platelet concentration and volume of the platelets produced by the occasional staff were out of control, which was not the case with the experienced staff. Introduction of control charts to a small blood centre has elucidated the difficulties in controlling the blood production and shown the advantage of using experienced regular component manufacturing staff.

I08 Development of transfusion medicine in Europe A challenge for physicians, scientists and politicians

Modern transfusion medicine in Europe has successfully handled the major threats to a safe blood supply by “classical viral” transfusion-transmitted pathogens like HCV and HIV. However, this was only managed by utilizing major financial and expert resources. Today, European harmonisation of optimal use of blood components in clinical hemotherapy, uniform quality standards for blood donations, testing and component production as well as an increasing cost pressure in clinical care are tasks, which need our full attention. Modern cellular therapies and regenerative medicine are novel treatment options, which can only be handled by a close cooperation between clinicians and transfusion medicine specialists. Future challenges comprise proactive measures like pathogen inactivation for all blood components in order to diminish threats to blood safety by (re-)emerging pathogens, an adequate blood supply bearing in mind the ongoing ageing of most European populations and political decisions regarding a potential open “blood market” in Europe, which in our opinion should not be supported by the European Union.

The different tools in quality management

Background Since the mid 1980s hospital‐based blood banks, all parts of the public healthcare system in Denmark, have been inspected regularly by the Danish Medical Agency, a division of the National Health Authority. Blood components for transfusion were regarded as medicaments and should therefore fulfill some pharmaceutical requirements.Evolution From the time of ‘the surgical approach’ to blood transfusion, i.e. drawing whole blood and using it as such for treatment, a process of refinements have taken place within all aspects of transfusion medicine in the blood bank setting in Europe. In Denmark, blood banks are separate hospital departments covering all aspects of the transfusion activity with specially trained medical doctors (separate medical specialty), donor selection, production of blood components, testing for selected infectious markers, blood grouping and compatibility testing, investigation of adverse reactions/complications to transfusions and constructive dialogues with representative users of the services from the blood bank and blood bank personnel in the Hospital Transfusion Committees to secure appropriate use (clinical doctors and nurses) and relevant accessibility of blood components and laboratory testing (the blood bank output). At present, the level of implementation of quality management in transfusion centres in Denmark is at the accreditation level with reference to the EU Blood Directives the Danish Blood Law and orders in many aspects equivalent to the ISO 15189 standard.The tools of quality management The overall demand is to go ‘one‐way’. This can be achieved by having a quality manual (overall objectives), master description of procedures (master plans), standard operating procedures (SOPs) and a well‐prepared feedback system using quality control measurements of blood components and laboratory tests, through reports of variations (deviation from intended result or SOP), complaints, systematic internal audits, updated educational records of all personnel involved in the activities of the blood bank (nurses, secretaries, laboratory technologists, medical doctors, others), assurance that all equipment and utensils are only taken in use after proper validation/qualification and that a maintenance plan or acceptance test are in action. Furthermore, a relevant number of external proficiency testings are carried out to secure the analytical quality of all key parameters in the laboratory. Every second year the blood bank will be inspected by the Danish Medical Agency and identified issues must be addressed in a written response within a time limit. The issues pointed out can deal with the building, personnel, apparatuses, equipment, utensils, processing, data management, corrective actions and other issues relevant for the fulfillment of the requirements of a European blood bank setting in 2007. In addition, the area of transfusion is surveyed at a national level (blood components/blood donor accidents/clinical practice of transfusion treatments).Conclusions The benefits of quality management surpass the costs by creating high‐quality products and services for the benefit of patients, blood donors, hospitals and personnel in the blood bank.

European best practice in blood transfusion: improvement of quality‐related processes in blood establishments

Transfusion medicine is an expanding field comprising the interaction between several medical disciplines. Looking at the ‘vein to vein process’ covering the donation of blood by the voluntary donor up to the application of blood components to patients, modern blood transfusion services comprise a large variety of sociomedical functions. The production of standard cellular blood components, such as erythrocyte and thrombocyte concentrates, plasmatic blood components as well as special cellular components such as blood stem cells, mesenchymal cells or granulocytes will require an extensive laboratory testing repertoire to monitor product quality and safety. The European blood legislation has defined several key quality elements to achieve good manufacturing practice in the field of blood transfusion. In addition, GMP/GLP and ISO standards are used inter alia by blood establishments. Following the call for proposal in the field of public health by the European Commission, a consortium of blood establishments from 16 European member, acceding and EFTA states has been established in order to survey the individual quality management systems used by the participants and to developed guidelines for quality systems. These guidelines are aimed at assisting blood establishments in preparing for government inspections as required by Directive 2002/98/EC. They could also be used to adapt existing procedures to comply with current EU requirements and/or to prepare for accreditation and certification of these institutions. Major benefits from those quality management systems are (1) the definition of an overall quality policy, (2) improved personnel responsibility, qualification and training, (3) error and risk assessment system, (4) continuous improvement, (5) improved resource management, (6) performance improvement. The definition of cost–benefit relation between certification and accreditation of blood establishments will depend on the individual institution itself and the amount of processes covered. With the release of the new EU Directive 2005/62/EC, there are currently EU requirements available that describe in detail relevant processes to be covered by quality system following good practice used in blood establishments. A future challenge for transfusion medicine would be optimizing the synergetic effects expressed by the EU directive, GMP and ISO standards.

Blood transfusion in Europe: basic principles for initial and continuous training in transfusion medicine: an approach to an European harmonisation

Over the past few decades, transfusion medicine and haemotherapy have evolved into complex medical disciplines comprising a broad field of subspecialties such as immunohaematology, blood component production, haemapheresis and haemostaseology. Transfusion medicine is thus an important qualification at the interfaces of analytical laboratory medicine, pharmaceutical production and clinical disciplines such as internal medicine, anaesthesiology or surgery. Physicians specialising in transfusion medicine are valuable and competent partners for these related disciplines when it comes to safe, effective and tailored haemotherapy. Why has transfusion medicine become so complex? On the one hand, one can discern problems such as infectious diseases like the HIV disaster in the past century, resulting in guidelines, directives and laws such as the transfusion law in Germany. Thereby, we now enjoy the highest level of blood product safety ever regarding viral transmission thanks to the broad implementation of PCR testing. On the other hand, there are numerous positive reasons for the increasing complexity of transfusion medicine: Modern medical therapies like stem cell transplantation, cellular therapy, transplantation of solid organs, regenerative medicine and surgery cannot exist without a safe supply of blood products and high quality standard as well as special blood products and laboratory services provided by blood banks and transfusion medicine specialists. Good laboratory practice (GLP), good manufacturing practice (GMP), quality management systems and quality control on the pharmaceutical manufacturer’s level are only few examples of the standards in today’s blood banking. European directives in the field of blood products, stem cell preparations and tissue have led to higher uniform quality standards for biological preparations in a unified Europe, which is the desired outcome, but which also increases the complexity of this field. In contrast, directives 93/16/EEC and 2001/19/EC, the directives of the European Parliament and of the Council on the mutual recognition of professional qualifications of European doctors currently in force, as well as the impending directive 2005/36/EC, which has to be translated into national law until October 2007, do not include transfusion medicine, blood transfusion or immunohaematology at all. Other medical specialities, which like our field, are not common to all member states of the European Union, are listed in the above mentioned directives with the minimum length of training and minimal requirements for the qualifications. Examples include clinical biology, biological haematology, microbiology–bacteriology, biological chemistry, immunology, thoracic, paediatric or vascular surgery as well as physiotherapy, stomatology, neuro-psychiatry, dermato-venerology, occupational medicine, allergology, geriatrics, gastro-enterological surgery, community medicine, nuclear medicine, pharmacology, accident and emergency medicine or tropical medicine. Most of the above are medical specialities in some member states, but not in all. A concerted initiative inaugurated by the European Network of Transfusion Medicine Societies (EuroNet-TMS) and the European Blood Alliance (EBA) aims to compile the situation of the transfusion medicine speciality throughout Europe. A preliminary summary of the current situation in 15 European states was prepared in 2005 after a first set of questions, which was sent out by us via the EBA platform. The authors appreciate Clair Watts’ compilation of the answers provided by the 15 European colleagues. A summary of these answers is depicted in Table 1. However, the initiative aims at a more complex analysis of the different requirements and constituent parts of the qualification in transfusion medicine in different countries. A long-term objective of this initiative might be to introduce the transfusion medicine specialisation into the above mentioned EC directives in order to facilitate mutual recognition of transfusion medicine qualifications throughout Europe.

Bacterial contamination of platelet concentrates prepared by different methods: results of standardized sterility testing in Germany

National guidelines for monitoring the bacterial contamination rate of blood components were introduced in Germany in 1997. The objective of this study was to present and evaluate the results of sterility testing of platelet concentrates (PCs) prepared by different methods. The analysis of results of sterility testing of blood component production from transfusion medicine centres in Germany in 1998 and 2001 was based on information collected using standardized questionnaires. The bacterial contamination rates for single-donor PCs derived from whole blood and apheresis (0.210% vs. 0.156%) were comparable and showed no significant difference. However, pooled PCs produced from four buffy coats using the sterile docking procedure showed a significantly higher bacterial contamination rate compared with single-donor PCs derived from whole blood and apheresis (0.184% vs. 0.604%). Use of standardized methods for sterility monitoring is sufficient to assess collection and production processes in terms of hygiene and yields reliable data on bacterial contamination rates of blood components. The methods described are suitable for using to analyse the efficiency of newly introduced methods to reduce bacterial contamination rates of blood components (e.g. diversion, bacteria screening and pathogen inactivation).

Alleviating blood shortages in a resource‐constrained environment

The nation devotes considerable resources to the collection, processing, and distribution of blood products. Nonetheless, shortages of virtually every blood component persist. Economic theory suggests that the national blood supply can be increased either by increasing the level of resources used in the collection and production of blood components or by utilizing existing resources more efficiently. This study uses data envelopment analysis to analyze the efficiency of 70 blood centers to determine the extent to which operational efficiency can be improved, the increase in the nation's blood supply that would result, and management strategies that would lead to such improvements. Data were collected from the AABB 2002-2003 Directory of Community Blood Centers. The study found that roughly half of the 70 blood centers studied are efficient. The remaining blood centers collectively can both increase outputs and decrease some inputs. If the inefficient blood centers were to eliminate half of their inefficiency, then systemwide output of platelets would be increased by 17 percent, cryoprecipitate by 12 percent, plasma by 10 percent, and red blood cells by 7 percent. Inefficient blood centers have little opportunity to reduce full-time employees or reduce expenditures; however, they can decrease their use of part-time employees by 10 percent and volunteers by 9 percent. The results indicate that efficiency improvements would help to alleviate the nation's persistent blood shortages. These findings can be used by blood center managers to identify management interventions that can improve operational efficiency, resulting in greater output with existing levels of resources.

ＣＰＤ液で採血した血液の全血処理型白血球除去ＷＢＦフイルタークローズドシステムの性能評価

To prevent the post-transfusion reactions in transfusion therapy such as HLA alloimmunization, non-hemolytic febrile transfusion reaction (NHFTR) and Cytomegalovirus transmission, bedside leukocyte reduction has been performed. However, it has become clear that prestorage leukocyte reduction has greater efficiency than poststorage, and prestorage leukocyte reduction is now being considered for implementation. We developed a prestorage leukocyte reduction system that contains CPD anticoagulant solution (PLD-C system). In this study, the performance of the PLD-C system was examined with regard to the leukocyte filtration efficacy and the characteristics of blood during storage by comparison with a pre-storage leukocyte reduction system which uses ACD-A solution (PLD-A system) and blood components collected using CPD solution and prepared by the buffy-coat depleted method (BCPD).It was confirmed that the leukocyte reduction ratio of the PLD-C system (more than-4log) was higher than that of the BCPD (less than-0.4log). Platelet depletion rates of the PLD-C group (average more than 99%) was also higher than in the BCPD group, but the red cell recovery ratio was the same between groups (average 88%). Prestorage filtration showed no adverse effects such as hemolysis, whereas various good effects were observed, such as inhibition of macroaggregate formation and hemolysis during storage. Collecting blood into CPD solution improved red cell quality during storage and increased plasma volume compared to the ACD-A solution.It was confirmed that the PLD-C system has advantages in the production of blood components over the present system. Use of this system can be expected to prevent post transfusion reactions.

強力化学療法と同種骨髄移植療法が施行し得たｌｇＡ欠損症を伴う急性骨髄性白血病の１症例

Deficiency of IgA with circulating class-specific anti-IgA antibodies is one of the major causes of anaphylactic reaction in transfusion medicine. This problem is more serious in the management of patients with hematological malignancies or other types of bone marrow failure. Here we report a case of acute myeloid leukemia with IgA deficiency who underwent intensive chemotherapy and allogeneic bone marrow transplantation. To avoid the production of anti-IgA antibody, platelet concentrates were collected from donors who were IgA-deficient. Additional support with platelets and RBC components from donors who had circulating IgA was provided using products washed and replaced with 0.9% normal saline. Complete remission was achieved after a single course of remission induction therapy. After one course of consolidation chemotherapy, allogeneic bone marrow transplantation from an HLA-matched sibling was performed. No anaphylactic reaction was observed after any transfusion. No circulating anti-IgA antibodies were detectable after the full recovery of hematopoiesis in this patient. These findings indicate that allogeneic blood component products collected from donors with IgA deficiency are useful in myeloablative therapy in patients with hematological disorders. By washing with normal saline, products from donors with normal IgA levels are also acceptable. Further studies to elucidate the clinical usefulness of precise genomic and expressional analysis of IgA gene are required to ensure the safety of transfusion medicine in patients with IgA deficiency. Furthermore, the establishment of blood bank registry systems for IgA-deficient blood donors is important to the maintenance of a stable supply of blood components for IgA-deficient patients who require transfusion therapy.

Rossi's Principles of Transfusion Medicine

3rd ed, edited by Toby L. Simon, Walter H. Dzik, Edward L. Snyder, Christopher P. Stowell, and Ronald G. Strauss, 983 pp, with illus, Philadelphia, Pa, Lippincott Williams & Wilkins, 2002.The 3rd edition of Rossi's Principles of Transfusion Medicine is intended as a resource for clinical transfusion medicine professionals. This multiauthored text contains 983 pages divided into 66 chapters that are, in turn, organized into 6 sections: “Blood Components and Derivatives,” “Clinical Practice,” “Apheresis,” “Adverse Sequelae,” “Special Topics,” and “Delivery of Blood Services.” Each chapter begins with an outline of the material covered in the chapter. There are flowcharts, graphs, tables, and photographs to enhance the reader's understanding in a number of chapters. The references have been reduced to those the authors consider most useful. New to this edition are chapters on specialized therapeutic apheresis procedures, prion transmission, and pathogen reduction as well as an expanded review of transfusion-transmitted diseases.The book provides an overview of technical topics rather than detailed step-by-step procedures. The “Red Blood Cell” section includes production, hemoglobin and oxygen transport, liquid and frozen preservation methods, erythrocytosis, anemia and red blood cell substitutes, and compatibility testing. The chapters on the blood group systems are organized by carbohydrate-based blood groups, Rh and Lewis systems, and protein-based blood groups. The platelet chapters cover production and hemostasis, immunology and alloimmunization, and platelet preparation, storage, and transfusion, including alternatives. White blood cell topics include neutrophil production, collection, transfusion, and leukocyte reduction of blood components. Plasma topics include the composition of plasma, the preparation of derivatives, immunoglobulins, and plasma transfusions and alternatives.The clinical practice section is divided into 4 sections: the transfusion issues of medical patients including autoimmune hemolytic anemia, immune thrombocytopenia, and coagulation defects; pediatric, obstetric, and congenital issues, including prenatal transfusions, and congenital disorders such as clotting protein deficiencies and hemolytic anemia; oncology patient transfusion needs including routine transfusion support, the use of growth factors, processing and preserving progenitor cells, autologous and allogeneic stem cell and marrow transplantation, adoptive immunotherapy, and gene therapy; and surgery patient issues, including perioperative red blood cell and coagulation support and the transfusion support of solid organ transplantation, as well as trauma and burn patient transfusion issues.The section “Adverse Sequelae” covers disease transmission and transfusion reactions. Included in the disease transmission group are the usual chapters on hepatitis, cytomegalovirus, and retroviral viruses, along with chapters on parasitic infections, prions, bacterial contamination of blood components, and pathogen inactivation. “Transfusion Reactions” covers hemolytic, febrile, allergic, and nonimmune reactions as well as graft versus host disease and transfusion-associated immunomodulation.Section V includes red blood cell radiolabeling and in vivo kinetics, HLA antigen and molecular testing, parentage testing, tissue banking, and medicolegal aspects of blood banking. The final section provides an overview of how blood is provided in both the United States and internationally, current good manufacturing practices, issues related to the hospital transfusion services, and quality assurance.The text covers a wide range of topics in transfusion medicine. The addition of clinical case studies makes this text more useful as a teaching tool. It would be useful in a physician training program as a primary resource for clinical issues in transfusion medicine and a valuable addition to any transfusion medicine library.

Multivariate predictors of blood product use in cardiac surgery

Objective: To determine factors associated with an increased risk of post-cardiopulmonary bypass (CPB) blood product usage in adult cardiac surgical patients. Design: Prospective observational study. Setting: Academic hospital. Participants: Patients undergoing cardiac surgery with CPB were studied over a 7-month period. Interventions: The outcomes studied were receipt of more than 2 U of packed red blood cells (PRBCs), receipt of any other blood component products (cryoprecipitate, fresh-frozen plasma [FFP], or platelets), or surgical re-exploration for bleeding. Preoperative and intraoperative risk factors for bleeding were analyzed. Measurements and Main Results: Increased age and preoperative creatinine level, low body surface area, preoperative hematocrit, nonelective surgery, lower temperature on bypass, and duration of bypass were associated with an increased risk of transfusion of >2 U of PRBCs. Low body surface area, repeat surgery, nonelective surgery, and CPB time were associated with transfusion of platelets, fresh-frozen plasma, or cryoprecipitate and/or surgical re-exploration. The following factors were associated with neither transfusion of more than 2 U of PRBC nor transfusion of platelets, FFP or cryoprecipitate, or surgical re-exploration: gender, preoperative international normalized ratio, preoperative antiplatelet medications, and preoperative intravenous heparin. Conclusion: Therapies aimed at reducing transfusion of blood products should be aimed at those patients with low body surface areas, baseline anemia, and those undergoing long or repeat surgeries. © 2003 Elsevier Inc. All rights reserved.

DART–A Voluntary System of Hemovigilance in Denmark

SUMMARyDenmark has a long tradition of collecting information concerning the country's activities, and this includes the collation of data concerning transfusion medicine. Data concerning nearly all parts of the transfusion chain, from the giving of blood through to the production of blood components and to the registration of transfusion complications, has been collected for years. Some data is provided on a voluntary and confidential basis by non‐official bodies, whereas official bodies as a legal obligation provide other data. Up to this day, a common national hemovigilance system has not been established.The Danish Registration of Transfusion Risks (DART) was initiated in 1998.The inspiration to initiate a registration of risks in connection with blood transfusion came from the results published by SHOT and from France. The British system SHOT was focused on, because the idea of a voluntary and confidential system was more suited to the Danish mentality, and was therefore more likely to be generally accepted. The DART system was originally organized as a copy of SHOT with the intention of making it possible to compare results from the two systems.During the first four years DART received 114 reports (91 about a severe risk). Half of the severe events concerned the transfusion of an incorrect blood component, and the other half were concerned immunological complications. Only 5% of the reported events concerned transfusion transmitted infections. The results obtained by DART have given rise to initiatives and recommendations aimed at reducing the transfusion risk.

Monitoring universal leucodepletion performance: the current issues within components production and testing

The UK NBS completed the introduction of universal leucodepletion in November 1999. This involved the implementation of new methods of production, testing and monitoring, the development of which is still ongoing. Whilst important lessons have been learnt, much remains to be achieved in respect of quality improvement through standardisation of procedures, processes and product modifications to improve safety/efficacy of therapeutic blood components. Since the introduction of universal leucodepletion, many changes in component production and testing have occurred. The primary goal of this report is to review the level of standardisation and harmonisation currently achieved for low leucocyte counting within the NBS and discuss remedial actions undertaken to improve the standard of blood component production and quality monitoring and to highlight some of the related issues which are currently being worked on. The following issues are discussed.

A new blood donation strategy: Automated blood collection (ABC)

The aim of this study was to find out if Cobe Trima, a blood cell separator that automatically collects RBC, PLT and plasma, is adequate for routine multiple blood donation by apheresis. Eighty donors underwent multiple blood component donations by Cobe Trima. Blood counts were determined on the apheresis products to analyze their quality. Eighty procedures were performed collecting 193 products. The average platelet yield was 3.5x10(11) (+/- 0.46) in the 54 single product (SP) procedures and 7x10(11) (+/- 0.88) in the 26 double product (DP) procedures. WBC contamination of the PLT products was 1.7 x 10(5) (1.2-4.2). The mean platelet efficiency was 60 +/- 8.35% for SP and 66 +/- 9.59% for DP. The hemoglobin (Hb) content per unit was 46.21 g (+/- 7.84) in 8 DP and 40.82 g (+/- 6.41) in 34 SP procedures. The production of standardized blood components with good PLT yield and low WBC contamination plus high efficiency makes Trima one of the best blood cell separators of the new generation.

PCR testing of plasma pools: From concept to reality

A NUMBER of factors might be considered to have contributed to the current drive to: the ~mplememation of genomic testing for hepatitis C virus (HCV) RNA within the field of transfusion medicine. The apparent urgency to establish effective systems aimed at the detection of seronegative, yet infectious, units is evident within the United States and in Europe. In both instances. concern initially relating to plasma destined for fractionation is now clearly impacting on blood services whose primary focus is the production of labile blood components. This review outlines the background to the development of current regulatory requirements and assesses the options that will enable transfusion services to ensure compliance, both the currently available option and~ those under development.

Preparation and preservation of red cells.

The production of blood components has undergone several changes during the last decades. Red blood cells will have slightly different properties depending on the way of preparation: whether a hard or soft spin has been used, whether platelets and/or leukocytes have been removed or not, and whether the red cells have been suspended in part of the original plasma or in an additive solution. Automated techniques are now often used for the separation of buffy coats, red cells and plasma. Recently, apheresis techniques have been applied for the preparation of red cells, mostly in combination with plasma or platelets. Continuous addition of the anticoagulant during collection reduces the delay between collection and separation, but the cost is higher and donor time longer. Most of the methods for the preparation and storage of red cells allow 35-42 days of storage with a mean in vivo recovery of > 75%. However, the content of erythrocyte 2,3-DPG is commonly lost within 1-2 weeks, caused by the accumulation of acid metabolites, but can be maintained longer with new systems of storage. Leukodepletion of red cells by filtration is used increasingly, but its importance in the majority of transfusions is still unclear. New options for the preparation and storage of red blood cells are available and undergo continuous evaluation.

GMP in blood collection and processing.

The principles of Good Manufacturing Practice have, in the main, been universally developed for the guidance of the pharmaceutical industry rather than for transfusion services. However, these rules and guides are increasingly being adapted for use in blood centres, in the production of labile blood components and of plasma for fractionation. The guide for pharmaceutical industries produced by the commission of the European Communities is used as a model here, the nine basic requirements being those applicable to Quality Management, personnel, premises and equipment, document, production, Quality Control, contract manufacture and analysis, complaints and product recall, and self-inspection. Though having more direct application to the production laboratory preparing blood components, the majority of these requirements and principles are also directly applicable to all of the activities involved in blood collection.

Practical guidelines for process validation and process control of white cell-reduced blood components: report of the Biomedical Excellence for Safer Transfusion (BEST) Working Party of the International Society of Blood Transfusion (ISBT).

The increased use of white (WBC)-reduced blood components has prompted many institutions to develop quality assurance programs directed to such component preparation processes. For consistent preparation of WBC-reduced blood components that meet clinical needs as well as national standards, a program of process validation and control should be instituted. This involves controlling key factors that affect WBC reduction as well as periodic monitoring of the residual cellular content of components. Practical guidelines for the implementation of such a program are provided. A program involving three phases of monitoring was developed by individuals belonging to an international working party of the International Society of Blood Transfusion. The first phase, process validation, evaluates a minimum of 20 consecutive units (a minimum of 60 units when nonparametric measurements are used) to document the successful local implementation of a new or substantially modified process. Ongoing process control employing Levey-Jennings type control charts is used to demonstrate that the process remains stable over time. Process capability assessment and conformance with standards are evaluated once residual WBCs are counted in a sufficient number of units. This enables a facility to claim with a specified degree of confidence that a stated proportion of WBC-reduced units will meet national standards. Two approaches to determine the number of units that should be selected for counting are presented. The first approach considers units as either acceptable or not acceptable and assumes that the distribution of failed (or nonconforming) units approximates the Poisson distribution. The second approach takes into consideration the observed WBC content of the tested units, with the assumption that the residual WBC content in WBC-reduced components follows a lognormal distribution. A method to assess the lognormal distribution of residual WBCs is presented. Specific tables based on each of these approaches are provided to guide the reader in the design of a program that will verify conformance with any national standard at specific confidence levels. The approach can be generalized to other process control applications. Guidelines are presented for process validation, process control, and assessment of conformance in the production of WBC-reduced blood components. Policy makers retain the responsibility to establish, on the basis of the expected use of WBC-reduced components, requirements for the frequency of testing and for the proportion of prepared units that are expected with a stated degree of confidence to meet the standards. Facilities preparing WBC-reduced components can monitor key factors that influence the preparation of WBC-reduced blood, can periodically assess their conformance with the standards, and can intervene to correct adverse changes in the process. This approach can be used to ensure the consistent quality of WBC-reduced blood components.