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Our organisation - science put into practice
| How did the blood supply in the Netherlands come about and how is it currently organised? The blood supply in the Netherlands depends on voluntary blood donations. At the time of its foundation, the Blood Transfusion Service of the Dutch Red Cross chose the pelican as a symbol for the selflessness of voluntary blood donation. Since the Middle Ages, the pelican has been a universal symbol of altruism and charity. Legend has it that the pelican pecked her breast to feed her starving chicks her own blood. This legend probably stems from the fact that the pouch of the Dalmatian pelican (Pelecanus crispus) becomes blood-red during the breeding season. Even now, the pelican symbolises blood donation and therefore is the symbol of the current blood supply organisation: the Sanquin Blood Supply Foundation. However, the image of the pelican in the logo has changed through the years. The adaptation to different periods symbolises the evolution of blood transfusion technology. The history of blood supply in the Netherlands and the development of medicines from plasma The first Dutch Blood Transfusion Service was founded in Rotterdam in 1930. In subsequent years, other blood transfusion services were founded, for example in The Hague and Utrecht. The initiator was Dr. H.C.S.M. van Dijk, internist at the former Sint Franciscus Gasthuis in Rotterdam. During a stay in London, he investigated how the English Red Cross had organised its blood transfusion service. In 1926, the English Red Cross had taken over the blood transfusion service from the pioneer Percy Oliver, who had founded the first blood transfusion service in London in 1921. Back in the Netherlands, Van Dijk asked the board of management of the Dutch Red Cross to follow England’s lead and assume the organisation of blood transfusion services to be a ‘peace mission’. According to Oliver’s principle, blood should be donated voluntarily, and without compensation. The Dutch Red Cross also adopted this principle. The blood transfusion services ensured that selected donors would respond to calls to donate blood at regional hospitals. In 1939, the onset of World War II necessitated measures to prevent a shortage of blood. In co-operation with the medical service of the army, two ‘preservation’ centres were founded to meet the increasing demand for preserved blood. These were the forerunners of the current blood banks. One preservation centre was located in Rotterdam and supervised by Van Dijk, while the other was located in an attic of the Binnengasthuis Hospital in Amsterdam and managed by Dr. J.G.G. Borst. The centre in Rotterdam was destroyed during the bombardments of May 1940, but the conservation centre in Amsterdam survived the war and served as the foundation on which the Central Laboratory of the Blood Transfusion Service of the Dutch Red Cross (CLB) was established. Top CLB In 1947, the CLB began producing medicines from blood plasma by isolating various proteins from the plasma. In the steps following the isolation of a certain protein, another protein was isolated from the remaining plasma. In addition to this ‘plasma fractionation’ process, the CLB started a laboratory for blood group serology. In 1948, the CLB became an independent foundation in which three parties were involved: the Dutch government, the Dutch Red Cross and the municipality of Amsterdam. In the 1950s, diagnostic and scientific research at the CLB rapidly expanded, focusing on determining causes of problems in (blood) transfusion therapy. Significant areas of attention included blood group research, causes of transfusion reactions, immunisation during pregnancy and the functioning of the human immune system. During the same period, the production of medicines and blood group reagents received top priority. In 1959, the CLB moved to another location, the Plesmanlaan in Amsterdam. Due to the continued expansion of scientific activities, a separate CLB research foundation was founded in 1962. Named after Dr Karl Landsteiner, the discoverer of the AB0 blood group system, the Karl Landsteiner Foundation co-ordinated all scientific research within the CLB and was also responsible for fund-raising. At the end of 1993, a new plasma fractionation plant was opened, where high-quality plasma products are produced in accordance with such guidelines as the Good Manufacturing Practice (GMP) principles. At the same time, the diagnostic activities expanded significantly – each year, over 700,000 blood samples were tested, making CLB the largest specialised diagnostic laboratory in the Netherlands. Due to a great many pioneering and fundamentally applied research projects and many international partnerships, the CLB has become a leading institute in the field of transfusion medicine.
By the end of the 1990s, the CLB employed a staff of over 800. It focuses on seven core tasks in the area of blood and blood transfusion:
Top Blood Banks Through the years, the locations where the donation of blood is organised have been centralised. Until 1973, there were 110 Red Cross blood transfusion services in the Netherlands, which ensured that tested donors donated blood in hospitals on call. When it became technically feasible to store blood products, the regional organisation of the blood supply was given the go-ahead. Between 1973 and 1982, 22 regional blood banks were founded, each being an independent foundation managed by representatives of hospitals and the Red Cross. The regional blood banks performed many tasks, including the collection and testing of blood, the preparation of blood products from blood, and their storage and supply to hospitals. At the end of the 1990s, the merger into a single entity, the Sanquin Blood Supply Foundation, resulted in nine primary regional blood banks. In 2001, their activities were further centralised to increase the efficiency of the blood supply. This resulted in the creation of four major blood bank centres, each covering a large area of the Netherlands. There remain approximately 600 locations across the Netherlands where blood is collected from donors. Top The Sanquin Blood Supply Foundation
On 1 January 1998, the Blood Supply Act took effect in the Netherlands, replacing the Blood Transfusion Act of 8 November 1988. On the basis of the Blood Supply Act, the Minister of Health, Welfare and Sports charged one legal entity with responsibility for the blood supply in the Netherlands. This means that a single organisation estimates the annual need for blood and blood products, collects blood, and prepares and supplies blood and blood products. Conditional to these activities is that they be carried out on a non-profit basis and that blood be collected only from non-remunerated, voluntary donors. Another of the basic principles formulated in the Blood Supply Act is that the Netherlands should be self-sufficient with respect to blood products. On 1 January 1998, the Minister appointed the Sanquin Blood Supply Foundation (abbreviated to Sanquin) as the blood supply organisation described in the Blood Supply Act. Sanquin was founded as the result of a merger between CLB and the Dutch Red Cross blood banks. Sanquin adheres to the basic principles established by the International Red Cross. Sanquin’s mission statement is as follows: The Sanquin Blood Supply Foundation is responsible, on a non-profit basis, for the blood supply and for the promotion of transfusion medicine, in such a way as to meet the most stringent quality, safety and efficiency requirements. The foundation provides products and services, carries out research and provides education. The Sanquin organisation comprises several divisions (see illustration below). The four Sanquin Blood Banks are responsible for all Blood Bank activities in the North West, North East, South West and South East regions of the Netherlands. The activities of CLB are divided over Sanquin Plasma Products (formerly known as the CLB Products division), Sanquin Research (formerly known as the CLB Research division) and Sanquin Diagnostic Services (formerly known as the CLB Diagnostic Services division). Like the Blood Banks, these divisions are part of Sanquin.
Top Sanquin Blood Banks The four regional Sanquin Blood Banks are responsible for collecting of blood, preparing and supplying blood components to hospitals and intermediary products to Sanquin Plasma Products, which develops medicines from plasma. Other key activities of the blood banks include advising those who treat patients with blood products (clinicians; physicians etc.), conducting research and providing education and training. For more information see Blood donation. Top Sanquin Plasma Products Sanquin Plasma Products prepare plasma products, i.e. medicines developed from plasma. See for information about the activities of this division Blood products and Plasma fractionation. Top Sanquin Diagnostic Services Sanquin Diagnostic Services is the largest specialised diagnostic laboratory in the Netherlands. Here, a great many diagnostic tests are carried out for a large number of hospitals and health care institutes. The laboratory focuses on two areas of specialisation: diagnostic tests regarding abnormalities in the human immune system and diagnostic tests regarding blood transfusion. Sanquin Diagnostic Services meets the most stringent quality requirements and acts as a diagnostic reference centre in both the above diagnostic areas. In more detail, the diagnostic activities focus on the following areas:
Nearly all health care institutions in the Netherlands regularly call upon the services of Sanquin Diagnostic Services. In addition, it acts as a reference laboratory in the field of blood group typing and unexplained blood transfusion reactions. This means that hospitals can call upon the knowledge and expertise of Sanquin whenever they encounter problems related to blood transfusion and immunology. The European Bank of Frozen Blood of the Council of Europe is also located at the Sanquin Diagnostic Services laboratory. Under the supervision of the Council of Europe, Sanquin is responsible for storing a panel of red blood cells from donors with very rare blood groups. These cells are stored at a temperature of -196°C, in liquid nitrogen. If rare red blood cells are required anywhere in Europe, Sanquin ships these to the country in need. In addition, Sanquin Diagnostic Services has several advisory functions. In 1976, the World Health Organisation (WHO) appointed the CLB as International Laboratory for Biological Standards for human blood and blood components. Sanquin Diagnostic Services prepares and manages these internationally recognised standards. The biological standards contain a fixed and recognised quantity of a certain material, for example a certain protein, which serve as a kind of ‘golden standard’ against which biological preparations are calibrated. Top Sanquin Research Sanquin Research is involved in basic and applied scientific research, training and education. All research in this division is related to the many aspects of blood and blood transfusion. The research departments support the Sanquin objectives regarding a safe and sufficient blood supply of the highest quality. Accordingly, Sanquin Research provides a scientific foundation for the products and services of Sanquin Plasma Products, Sanquin Diagnostic Services, Sanquin Reagents and the four Sanquin blood banks. Departments Collaboration in research, education and training Sanquin Research consists of the following departments and portfotios:
Plasma Proteins The research of this department addresses a variety of blood plasma proteins, in particular constituents of the coagulation system – the clotting mechanism of the blood. Research within this field of interest is multidisciplinary, comprising protein chemistry, enzymology, vascular biology and immunology. The programme is closely related to the production by Sanquin of pharmaceutical plasma proteins from human plasma. Top Transfusion Technology Research in this department focuses on optimising whole blood donations and on safety issues regarding cellular blood products (especially red blood cells and platelets). The department consists of two laboratories: Blood Transfusion Technology and Cryobiology. The latter is related to the activities of Sanquin for the European Bank of frozen Blood of the Council of Europe. Top Experimental Immunohaemotology The research programme of the Department of Experimental Immunohaemotology includes studies regarding alloimmunity against blood group antigens, stem cell transplantation, leukocyte-vascular wall (endothelium) interaction, functions of granulocytes and red blood cells. Top Immunopathology This department comprises of three laboratories: Allergy, Autoimmune Diseases and Pathophysiology of Plasma Proteins. Key research activities of the Allergy group traditionally focus on the responses in the immunoglobulin classes IgE and IgG in both healthy and allergic individuals. The main line of research of the Autoimmune Diseases group has been to unravel the aetiology and pathogenesis of human autoimmunity. The Pathophysiology of Plasma Proteins group assesses the diagnostic and prognostic value of circulating granzymes, a group of enzymes involved in the defence against human diseases, in particular viral infections. Top Clinical Viro-Immunology The major research themes of this department centre on the immunopathology and pathogenesis of HIV infection. Moreover, immunity against other viruses, such as the Epstein Barr virus (EBV) and cytomegalovirus (CMV), is studied in relation to the pathogenesis of AIDS and other clinical diseases. Another line of research focuses on prion-related diseases, including (variant) Creutzfeldt-Jakob disease. Within this department, the Virus Safety Services group is dedicated to conducting virus validation studies regarding plasma-derived products and other biologicals. The group has broad experience in the validation of various process steps, and offers tests for a range of viruses, which meet the latest requirements of national and international regulatory bodies. Top Biotechnology The department of biotechnology is a business unit specialising in a broad array of pharmaceutical services aiming at the development of biologicals intended for therapeutic application in humans. These services include the contract production of monoclonal antibodies and recombinant DNA products, as well as safety testing and validation of such products. Top Quality Assurance This department is responsible for all quality assessment activities carried out in the Diagnostic Services and Research divisions of Sanquin. The activities necessary for this task in quality assurance are divided into two main areas: Quality Assurance and Documentation Management. The department is responsible for the establishing, implementing and improving of the quality assurance system according to the criteria of the Dutch Council for Accreditation. In order to maintain and increase quality, the department performs internal audits, and also audits suppliers and hosts external quality audits. Top Collaboration in research, education and training Sanquin Research closely co-operates with the Academic Medical Centre (AMC) of the University of Amsterdam in the joint Landsteiner Laboratory, located at the Sanquin premises in Amsterdam. Sanquin Research collaborates with many other research groups, both within the Netherlands and abroad. A number of staff members of the division hold professorships at major universities in the Netherlands. Staff of the division is involved in training students in biomedically oriented studies at universities and colleges. Every year, more than ten PhD students complete their training by defending a PhD thesis. Staff of the division is involved in post-doctoral and specialist training of workers at various levels in the health care system. In addition to the research activities at Sanquin Research, the Sanquin blood banks also perform research, often in collaboration with university hospitals in their region. In addition to clinical and applied studies focusing on cellular products, research in the area of humanities is undertaken to ensure the maintenance of donor availability and donor management. Many of the research projects are funded by charities, including the Dutch AIDS Fund, the Dutch Cancer Society, the Dutch Heart Foundation and the Dutch Kidney Foundation. In competition with other research groups, funding is also obtained from the national research council. Sanquin Research undertakes collaborative efforts with third parties, such as life-science start-ups and pharmaceutical companies, with respect to co-development, contract research, and licensing in the field of blood supply and transfusion medicine. Top Sanquin Reagents Within Sanquin Research, the Sanquin Reagents business unit is responsible for the production and marketing of reagents for diagnostic and research purposes. Over the years, various reagents have been successfully produced with a focus on serology and diagnostic tests regarding diseases related to the human immune system. These products are used in many diagnostic and research laboratories all over the world. Sanquin Reagents is certified according to ISO 9001. The products are divided into four major categories: Blood grouping reagents Human IgG subclass reagents Cytokines and related products Cell-specific monoclonal antibodies/granzyme antibodies Blood grouping reagents Blood grouping reagents are essential tools for diagnostic laboratories specialised in immunohaemotology. The reagents are used in various serological tests, in particular those to determine compatibility between patients and donors. It is essential to conduct these diagnostic tests prior to administering a blood transfusion with donor red blood cells and in special cases with donor platelets to prevent undesirable transfusion reactions in the patient. The blood grouping reagents comprise three product lines:
Top Human IgG subclass reagents Immunoglobulins are important proteins of the immune system. Immunoglobulin G is the major isotype of immunoglobulins in the blood. There are four subclasses of immunoglobulin G (IgG): IgG1, IgG2, IgG3 and IgG4. IgG subclass reagents are used to measure the concentrations of the four IgG subclasses in serum and to determine the subclass of antibodies. Deficiencies of one or more of the IgG subclasses are an indication that the immune system is compromised. Several diseases are associated with decreased or elevated levels of (one or more) IgG subclasses. The most conspicuous consequence of a deficiency of one of the IgG subclasses is a defect of the so-called humoral immunity, which is an important defence system against bacteria. However, this does not necessarily lead to clinical manifestations. Specific examples of diseases associated with decreased IgG subclass levels are bronchiectasis and severe, recurrent stages of otitis media, sinusitis, pneumonia and bronchitis. There are several methods to determine the quantity of IgG subclasses. Sanquin Reagents manufactures kits (ready-to-use assays) and reagents for the most frequently used techniques, including radial immunodiffusion, ELISA and nephelometry. Top Cytokines and related products Cytokines are a group of hormone-like proteins that are produced by a variety of cells of the immune system. They are soluble molecules, which mediate interactions between cells. Cytokines are involved in a large number of important cellular activities, including the maturation of blood stem cells, the induction of cell proliferation, the maintenance of cell viability and the regulation of immunity and inflammation. Quantification of cytokines is an increasingly common activity of many diagnostic and research laboratories. Originally, only the biological activity of cytokines could be detected, but nowadays the cytokines themselves can be detected using highly sensitive immunoassays developed by Sanquin. Top Cell-specific monoclonal antibodies/granzyme antibodies Cell-specific monoclonal antibodies are specifically directed against typical cell surface structures (antigens). Cell surface molecules of leukocytes and platelets are called CDs. They can be distinguished by using specific monoclonal antibodies. With these reagents, cell populations can be differentiated and different types of leukocytes can be distinguished and isolated from the blood. Granzymes are enzymes (proteinases), which are released by cytotoxic lymphocytes, important cells of the immune system. Granzymes enhance the ability of these cells to lyse virally-infected cells. Reagents for measuring granzymes are important in both fundamental research on cell death and applied clinical research. The broad range of cell-specific monoclonal antibodies and granzymes are the result of Sanquin’s long history of research into human leukocytes. Whereas the development of the first cell-specific monoclonal antibodies goes back as far as the early 1980s, antibodies against granzymes are the result of current research. Top For more information To request more information on the activities of the Sanquin divisions, please use the following e-mail addresses:
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