Transfusion Medicine of Today and the Future1

There are many examples of how work in the basic sciences has had a major impact in transfusion medicine. For example, understanding of platelet structure function, physiology, and the role of membrane phospholipids have led to improved platelet preservation. Studies of red cell structure and hemoglobin function have led to improved red cell preservation, an appreciation of the control of oxygen release by stored red cells, and have been the basis for development of red cell substitutes, although this work has been difficult and progress is slow.^2-4 Molecular genetics and sophisticated biochemical techniques have made it possible to identify the composition and structure of many blood group antigens and even the function of some of these molecules.^5,6 Improved understanding of immunology has added to the ability to manage and prevent alloimmunization, although interestingly more than 40 years after the clinical availability of Rh (Rhesus) immune globulin for the prevention of hemolytic disease of the newborn, its basic mechanism of action is not known. Studies of the immunologic effects of transfusion have not yet defined completely the molecular and cellular basis of the response but will ultimately answer present unresolved issues regarding the role of transfusion in postoperative infection, cancer recurrence, and the success of transplanted organs. ^7,8 Other developments in basic immunology are being translated into clinical practice through studies of adoptive immunotherapy. Biochemistry is the basis of exciting work on inactivation of viruses and bacteria in traditional cellular blood components.⁹ New strategies for donor testing using molecular diagnostic methods to identify donors in the window phase of infection are based on biochemical, immunologic, and molecular biologic techniques developed in the basic science laboratory to detect DNA (deoxyribonucleic acid) or RNA (ribonucleic acid).¹⁰ The basic scientific studies identifying and developing hematopoietic growth factors such as erythropoietin, granulocyte colony-stimulating factor, and platelet growth factors have had a huge impact on clinical transfusion medicine.^11-13 Cellular engineering using these and other hematopoietic growth factors and cytokines, along with an increased understanding of the 2mechanisms of cell division and cell culture techniques, are enabling transfusion medicine to provide novel blood components.¹⁴ Studies of the function of hematopoietic stem cells and lymphocyte function have led to the use of umbilical cord blood for hematopoietic reconstitution and the use of stem cells as a blood component.^15,16 Biochemical and cell membrane studies form the basis of efforts to enzymatically cleave ABO (group O, A, B and AB) antigens from red cells or to cover those antigens—two strategies for creating a universal red cell type.¹⁷

Examples of other types of transfusion medicine research sometimes carried out in collaboration with other disciplines include: biomedical engineering studies of blood filtration systems, apheresis technology and instrumentation, infusion pumps, blood testing instruments and blood warmers; translational research studies implementing pathogen inactivation technology; clinical laboratory research involving improved red cell, platelet and neutrophil serologic techniques; clinical trials of new blood components; blood collection techniques such as red cell apheresis; clinical studies of transfusion complications and reactions, and donor adverse reactions; epidemiologic studies of transfusion transmitted diseases, donor demographics and emerging potential transfusion transmitted diseases; and social science studies of donor motivation, volunteerism and the public's tolerance for risk.

Although its start was with Landsteiner's discovery of the ABO blood group system, now in the 21st century, transfusion medicine has progressed from its beginnings. Watershed discoveries in transfusion medicine include: the understanding of hemolytic disease of the newborn by Levine and Stetson, the development of plastic containers by Walter that made blood component therapy possible, the development of plasma fractionation by Cohn that led to the availability of plasma derivatives such as albumin, immune globulins and coagulation factor concentrates, the discovery of hundreds of red cell antigens, the development of Rh immune globulin that made hemolytic disease of the newborn a preventable disease, the development of blood cell separation equipment that made apheresis a routine method of preparing some blood components, understanding transfusion transmitted diseases and the development of strategies to minimize disease transmission, and the use of hematopoietic stem cells as a blood component. Today's transfusion medicine is sophisticated and complex hematotherapy involving an understanding of a variety of scientific disciplines in addition to the medical management of patients.

Component therapy for novel situations such as extracorporeal membrane oxygenators (ECMOs), more complex cardiovascular surgery such as placement of left ventricular assist devices, the continued expansion of hematopoietic cell and organ transplants and other medical advances will require transfusion medicine consultation. Implementation of 3these new technologies will require leadership from transfusion medicine/blood banking experts. Cellular engineering for production of new blood components is an area in great need of medical/scientific leadership for methods, development, problem-solving and laboratory management, and interaction with clinical physicians.

Many countries depend to a large extent on “family donations”—that is, blood donated by family or friends of the patient, but these friends are often paid by the patient's family to provide needed blood.^20,23 Many reports confirm that paid donors²⁴ and these “replacement” donors have a higher prevalence of transfusion-transmitted infection.^25-27 Thus, replacement donations in fact often constitute a hidden form of paid donation.²⁰ Creating a stable base of volunteer donors is the biggest challenge being faced in developing countries.²¹ A focus on developing a volunteer donor base is one of the most fundamental issues in developing a safe and effective blood supply. However, a sufficient number of well-trained donor recruiters to create an adequate blood supply is usually neglected or not available.²⁰ For instance, only 16 developing and least developed countries provide training for donor recruiters and there are few established posts for such individuals.²⁸

Laboratory testing for transmissible diseases is well-established, complex, and sophisticated. However, the enormous gap in the level of infections and available resources makes the screening strategies developed in Western countries both inadequate and unaffordable in developing countries.²⁹ Up to 13 million units per year of the global blood supply apparently were not screened for all relevant transfusion-transmissible infections during the 1990s.²¹ For instance, the WHO estimates that screening for human immunodeficiency virus (HIV) is carried out in 100 percent of developed, 66 percent of developing countries, and 46 percent of least developed countries, and hepatitis B in 100 percent of developed, 72 percent of developing, and 35 percent of least developed countries.²⁰ According to other WHO estimates, 43 percent of the blood collected in the developing world is not adequately screened.²¹ This means that about 80 percent of the world's population has access to only 20 percent of the global supply of safe screened blood.²¹ It is, therefore, critical for developing countries to design their own blood safety strategies adapted to their epidemiological, social, and economic circumstances instead of trying to reach the inappropriate standards developed by and adapted to developed countries.²⁹ For instance, rapid tests may be used in resource-poor settings and even done predonation so that infectious individuals do not go through the donation process.³⁰

The government's commitment is necessary to develop an effective blood program. Ultimately, the government bears the responsibility for the blood transfusion system regardless of the organization which is responsible for the implementation of the program. The resources important to blood centers are not only traditional quantifiable, such as financial and infrastructure, but others that are intangible or unquantifiable such as expertise and the local, social, and cultural settings; community understanding; and acceptance of blood donation.²¹ To some extent, these resources may be lacking in all countries, although in a different format. Another approach to matching blood supply and demand is “to ensure the rationale use of blood and blood products”.²¹ Most developing and least developed countries do not have transfusion guidelines or recommendations; and often, the transfusion 4medicine expertise necessary to educate physicians regarding the appropriate use of blood products is not available. Thus, transfusion medicine education programs for physicians who use blood for their patients can be helpful.