Preparation Of Blood Components Research Articles

From leukocyte reduction to leukocyte transfusion: the immunological effects of transfused leukocytes

In transfusion medicine, mononuclear leukocytes have been studied more often as contaminants of red blood cells or platelets responsible for adverse transfusion outcomes than as therapeutic cells; leukocyte transfusion has been effective in augmenting recipient immunity only in limited clinical situations. Studies in leukocyte reduction and leukocyte transfusion have progressed separately as if the leukocytes' adverse and therapeutic effects result from different immunological mechanisms. With growing clinical experience, however, it is increasingly clear that some adverse immune effects may be exploited for therapeutic benefit. Advances in clinical immunology, understanding of the variety of cells and functions in the leukocyte fraction of blood, and blood component preparation technology may lead to new ways of deriving immunological benefit from transfused blood leukocytes while minimizing their adverse effects. This chapter reviews the current uses of leukocyte reduction and mononuclear leukocyte transfusion, with an emphasis on the relationship between transfusion-associated graft-versus-host disease and donor lymphocyte infusion in controlling relapsed leukaemias.

Leukocyte-reduced blood transfusions: perioperative indications, adverse effects, and cost analysis.

Leukocyte-reduced blood transfusions: perioperative indications, adverse effects, and cost analysis.

Blood banking quality: minimum requirements for TQM

In 1995, the Council of Europe published a guide with recommendations providing transfusion services with a set of guidelines and principles relating to the preparation, use and quality assurance of blood components. As a blood transfusion service is at the same time a supplier of blood products and a test laboratory the quality management system must include good medical practice, good manufacturing practice and good laboratory service, all of which are closely linked. We made a critical evaluation of the content of the guide and analysed requirements and recommendations in comparison with quality management systems applied by the concerned partners. As a major critic we observed that the guide does not take into account any quality system of the in vitro diagnostic (IVD) supplier and/or distributor. With the addition of some items outlined in ISO 25 and ISO 9000, the Council of Europe document can be improved so that it complies with internationally accepted quality management standard recommendations.

Guide to the Preparation, Use and Quality Assurance of Blood Components

<i>Guide to the Preparation, Use and Quality Assurance of Blood Components</i>

Leukocyte-reduced blood products.

During the past 10 years, methods for blood component preparation have undergone considerable change. Refinements of traditional methodologies were necessary in response to demands for increasingly effective and safe platelet support for the intensive chemotherapy for patients with malignant disease, as well as a response to evidence of the immunological effects of whole blood or unmanipulated erythrocytes. At the center of the issue is concern for the consequences of transfusing contaminant leukocytes. Clearly, for all transfusions the lowest possible leukocyte content is desirable, and their removal should be as early as possible during storage. This review of recent journal articles focuses on reports of investigations of the effects of allogeneic leukocytes in blood transfusions. There is a sense of competition among the advocates for secondary elimination of leukocytes (by filtration) versus those favoring the approach of primary avoidance of leukocyte contamination (by centrifugation). As the following summaries indicate, the relative merits of leukocyte reduction by filtration, either before or after storage, versus leukocyte reduction by specialized apheresis methods remain undefined. The goal of a universal guideline for the use of leukocyte-reduced blood components is not yet achieved.

Guide to the Preparation, Use and Quality Assurance of Blood Components.

Guide to the Preparation, Use and Quality Assurance of Blood Components.

Recovery of extra plasma during preparation of platelet concentrates using a new centrifugation support.

During blood component preparation of standard blood donations a major loss of plasma occurs whenever platelet concentrates (PC) are produced, especially when the platelets are prepared by the platelet-rich plasma (PRP) method. This loss is partly due to the use of plasma for resuspension of the platelet pellet but the main loss is associated with the slow first spin used to prepare PRP. This slow first spin results in an undesirably low haematocrit and a red-cell concentrate which contains a large volume of trapped plasma which is lost to the fractionation plant. We have developed a method of recovering most of this plasma from the soft-spun red cells by including the red-cell concentrate (RCC) in the second spin during preparation of the platelet pellet. To allow recovery of the second spin plasma from the half-full RCC bag we have developed a simple bag support, the Perth BagRap. Development of the method proved difficult due to the high g forces but the final technique evolved was simple and inexpensive. The method was easily introduced into routine use and resulted in a 53% increase in plasma per three-product unit.

3a Emergency and massive transfusion

Emergency and massive transfusion represents a particular challenge for clinician and transfusion medicine specialist. The impressive improvements of blood component preparation and quality over the last 10 years have rendered most of the specific risks of massive transfusion negligible. Today specific risks caused by massive transfusion are only to be expected in case of very fast transfusion (replacement of one blood volume in 3–4 hours) and/or large volume replacement (two blood volumes in 24 hours). Furthermore, the individual situation of the patient is the main decisive factor in the outcome. On the other hand, emergency transfusion includes several particular risks which can only be sufficiently managed by appropriate organizational measures and defined replacement schemes. These are different in situations related to complications of elective surgery or to emergency admission. This article describes how to manage emergency transfusion under these different circumstances in order that the highest safety and rapid blood supply can be achieved.

Factors influencing white cell removal from red cell concentrates by filtration.

The preparation of blood components by hard centrifugation results in red cell concentrates with a small amount of plasma. The influence of various plasma factors, temperature, and storage time on white cell reduction by filtration was studied. Red cell concentrates were suspended in 100 mL of saline-adenine-glucose-mannitol (SAGMAN) solution or in SAGMAN solution in which 5 or 10 mL had been replaced with an equal amount of fresh plasma, albumin (4%), or heat-inactivated plasma. After overnight storage at 4 degrees C, filtration at a slow flow rate (2 hours) was performed. The effect of temperature was studied by filtration at 4 degrees C and 37 degrees C. To study the influence of storage time, red cell concentrates were stored for 4 to 8 hours or 14 to 20 hours at 4 degrees C and filtered through another model of filter. The number of white cells was counted microscopically or by flow cytometry. When 5 or 10 mL of plasma was added, a significantly smaller number of white cells were found after filtration than were found in the SAGMAN control (the median difference between pairs: 23.6 x 10(6) for 5 mL [p = 0.006] and 14.9 x 10(6) for 10 mL [p = 0.003]). The number of white cells was significantly higher with 10 mL of albumin than with 10 mL of plasma (difference, 15.0 x 10(6); p = 0.006). When heat-inactivated plasma was used, the number of white cells was significantly lower than when fresh plasma was used (difference, 0.3 x 10(6); p = 0.009). Filtration at 37 degrees C resulted in a 64-percent reduction in white cells and that at 4 degrees C led to a 99.7-percent reduction (p = 0.006). When the second filter was used, a slight but significantly lower number of white cells was found in the red cell concentrate stored for 14 to 20 hours than in that stored for 4 to 8 hours (difference, 0.03 x 10(6); p < 0.001). The amount of plasma in the red cell concentrate and the storage time and temperature are important factors in the outcome of white cell reduction by filtration. The effect of plasma does not seem to be due to a general influence of protein or to the activity of complement or fibrinogen.

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.

Quality assurance of bacterial incidents associated with blood transfusion

Transfusion associated bacterial sepsis, TABS, may be caused by-donor bacteremia,-bacteria from the donors skin,-bacteria brought by one of the persons handling the donation or the blood product, from collection and components preparation to the actual transfusion,-or bacteria introduced by a defect in one of the disposables used. Quality Assurance relies on the Good Transfusion Practices of the French Blood Agency all along the transfusion chain from the donor to the recipient. Active involvement of personnel, standardisation and controls as well as improvement of technics particularly as regarding donor selection, skin disinfection technics and collection are required. The ultimate control is hemovigilance with proper identification and investigation of all cases of TABS even with mild symptoms. Centralisation of data in the Haemovigilance scheme is a further step toward a better understanding and improvement of blood products bacterial security.

AN OVERVIEW OF THERAPEUTIC APHERESIS

Haemapheresis, or more generally, apheresis is concerned with the separation and differential separation of blood. It differs from dialysis, in that the process of separation concentrates mainly on cells and high molecular weight proteins. Correspondingly different separation techniques are used. Though apheresis can be performed applying conventional off‐line centrifugal techniques, it is generally associated with the use of on‐line centrifugation in blood cell separators (nowadays prefered to be called blood separators), plasmapheresis systems or devices for the preparation of blood components serving autologous blood transfusion. Filtration through flat sheet membranes or hollow fiber membranes is also applied. The differential separation of cells or plasma is off‐line and on‐line, correlating with the different degrees of technical maturation of the secondary separation systems. These secondary techniques aim at a concentration of certain cell types (for instance of stem cells) or at the elimination of undesired cells such as T cells or erythrocytes from stem cell or bone marrow concentrates. In secondary plasma treatement, filtration or adsorption procedures compete with immunological techniques and magnetic binding or density centrifugation or combinations of several techniques.

Modern Veterinary Blood Banking Practices and their Applications in Companion Animal Practice

There are two main reasons for blood component therapy: the need for an increase in oxygen-carrying capacity and improved hemostasis. Additionally, blood component therapy is used to increase plasma protein concentrations. Component therapy entails separating whole blood into its cellular and plasma components and administering the appropriate blood component based on the patient's needs. General considerations such as compatibility, defined expectations of benefits, and topics including specific disease screening, preparation of blood components, preparation of blood products for administration, and typing and crossmatching in relation to blood component therapy and its application in companion animal practice are discussed.

Blood Components: Collection, Processing, and Storage

Veterinary blood component preparation methods are based on human protocol with veterinary modification. This article covers the practical aspects of donor selection, blood collection, and the various options for separation of whole blood into components. Obligations are met to ensure high quality products yet allowances are made where possible to account for problems that are unique to veterinary medicine.

Blutspende nach Maß: Konzept für zeitgemäßes Blutspendewesen

‘Product-oriented Blood Donation’ is a concept of ‘heme economies’. It takes advantage of recent developments in preparation and storage of blood components at a time, when new therapeutic concepts, safety and cost concerns may dramatically reduce the need for allogeneic blood products in transfusion medicine. The concept facilitates substantial savings within the health care system. Simply, red cell and platelet concentrates for allogeneic transfusion therapy are prepared only from group 0 whole blood donated by volunteer non-remunerated donors. Suspending these plasma- and leukocyte-depleted blood cell preparations in the appropriate additive nutrient solutions renders them universally ABO-com-patible. Similarly, universally ABO-compatible fresh-frozen plasma for allogeneic transfusion is to be procured exclusively from group AB donors by plasmapheresis. Volunteer donors of all blood groups may qualify for donating HLA-compatible platelets by apheresis, as needed. The plasma derived from the group 0 blood donations will supply more than 50% of the source plasma needed for fractionation. The remainder may stem from first-time donors (blood group yet unknown), from AB apheresis plasma not qualifying for release because of no return of donor for retesting after quarantine storage, and from plasmapheresis of donors with blood groups A or B. In Germany, the current level of group 0 and AB donations is sufficient to supply the preparations needed for allogeneic transfusion. Approximately 50 plasmapheresis facilities will be operating soon. At this time, the German requirement of ABO-iden-tical allogeneic transfusion appears to be the greatest impediment for the concept of ‘Product-oriented Blood Donation’.

The quality of red blood cells.

The evolving practice of medicine has required a number of changes in red cell product manufacture to ensure that the final product is more specifically tailored to the needs of the individual patient. As a result of the increasing concern over the risks of transfusion pharmaceutical standards of manufacture are now applied to blood component preparation. Studies have been undertaken to define the optimum method of blood processing, and newer technologies are emerging to allow acquisition of a more consistent dose of red cells in a fashion which may minimize the lesion of collection. Use of high efficiency 3+ generation filter technologies reduces leukokine build up during storage and improves the quality and purity of the stored blood product. The combination of new plasticizers for packaging and improved red cell additive solutions should allow the blood center to supply a more functional red cell with longer storage shelf life. Overall these developments should result in the provision of a more consistent dose of fully functional red cells to the recipient who will be less exposed to the undesirable sequelae of transfusion than previously.

Biologic effects of leukocytes present in transfused cellular blood products

A considerable literature has accumulated over the past decade indicating that leukocytes present in allogeneic cellular blood components, intended for transfusion, are associated with adverse effects to the recipient. These include the development of febrile transfusion reactions, graft-versus-host disease, alloimmunization to leukocyte antigens, and the immunomodulatory effects that might influence the prognosis of patients with a malignancy. Moreover, it has become evident that such leukocytes may be the vector of infectious agents such as CMV, HTLV-I/II, and EBV as well as other viruses. An interesting development that has occurred coincidentally in transfusion medicine is that agencies responsible for the provision of blood products are being designated manufacturers of biologicals. The trend among manufacturers of biologicals is to try to produce pure products to provide for the specific therapeutic need of patients. Thus, with the realization that allogeneic leukocytes and their products may have adverse biologic activities, there is increasing pressure from various sources for the reduction of the leukocyte content in allogeneic blood components to minimize the occurrence of their adverse effects. Although the threshold leukocyte number below which these effects might no longer occur is still to be determined, a 2 to 3 log10 leukocyte reduction, provided by the currently available commercial leukocyte filters, has been shown to reduce the frequency of many of such reactions. On the other hand, the immunosuppressive effects produced by the infusion of allogeneic leukocytes might be beneficial for some patients, ie, for the maintenance of kidney allografts, in possibly reducing the relapse rate in patients with inflammatory bowel diseases, and in ameliorating recurrent spontaneous abortion. Moreover, therapeutic granulocyte transfusions may be of benefit in certain well-defined categories of patients infected with bacteria, yeast, and/or fungi. These include neonates with bacterial sepsis associated with bone marrow failure as well as severely neutropenic leukemic patients with an infection unresponsive to appropriate and specific antibiotic therapy. Many of the results obtained with the use of leukocyte depletion filters are tantalizing, but the actual clinical benefit of leukodepletion has not been established in most instances, because much of the available data are retrospective or from uncontrolled clinical trials. Moreover, issues of cost-effectiveness and quality control have not been considered adequately. Properly designed prospective clinical trials are essential to provide data with which to answer such questions and also to help define the optimal conditions required for the preparation of blood components ultimately destined for clinical use. Only with the availability of such data can sound decisions be made about the clinical value of leukodepletion.

Application of a commercial SPC software package to the preparation of blood components

Application of a commercial SPC software package to the preparation of blood components

Current Trends in Immunohematology and Transfusion Medicine

The procurement, processing, and provision of blood components continues to evolve and improve. New technologies and procedures for providing more efficient and effective testing are being implemented. Innovative practices and processes are being applied to the preparation and transfusion of blood components resulting in safer transfusion practice. Current management practice emphasizes the provision of better products and service in a more costeffective environment.

Transfusion of blood components to persons infected with human immunodeficiency virus type 1: relationship to opportunistic infection.

Although a recent study reported shorter survivals in human immunodeficiency virus type 1 (HIV-1)-infected patients who received transfusions, no study has analyzed the relationship in such patients between the frequency of opportunistic infection and transfusion. Records of 196 HIV-1-infected subjects with CD4 lymphocyte counts below 250 cells per mm3 were reviewed to determine if there were more opportunistic infections in patients who previously received transfusions than in those who received no transfusions. The decline in CD4 cells was also compared, and the frequency of transfusion reactions and red cell alloantibodies was assessed. The frequency of cytomegalovirus (CMV), wasting, and bacterial infections (p < 0.01), but not the frequency of Pneumocystis carinii pneumonia (PCP) (p > 0.2), was significantly increased in the patients who had previously received transfusions, and this effect was independent of CD4 count, race, or risk factor. The frequency of CMV infection, but not of PCP, was also related to the number of units of blood received (p < 0.01). Significant bacterial infections occurred primarily in persons with CMV infection, of whom there were more in the transfusion cohort. When analyzed separately in the group of patients without CMV infection, the frequency of bacterial infection was unrelated to transfusion. The death rate in those who received transfusions was also greater than that in patients who had never received a transfusion. None of the 130 patients who received red cell transfusions developed red cell alloantibodies. The higher incidence of certain infectious complications in HIV-1-infected patients who received transfusions indicates that the relationship of transfusion to virus activation in patients with acquired immunodeficiency syndrome and the potential benefits of modifying the preparation of blood components should be investigated further.