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Methods for selective blood component removal.

The objective of therapeutic Extra Corporeal Blood Treatment (ECBT) is the removal or conversion of unwanted (mostly pathogenic) substances present in blood. At present ECBT is generally performed by using physical techniques such as dialysis, membrane filtration and centrifugation. These techniques are characterized by a low level of specificity leading to simultaneous removal of useful compounds. Administration of large quantities of substitution fluids (e.g., plasma-exchange, hemofiltration), is therefore often necessary. Higher levels of specificity can be obtained by using specific binders. Recent results obtained with synthetic polymers show the high potential of this technique. The use of biological substances, such as enzymes and antibodies, will enable an almost 100% level of specificity. It is obvious that the natural defence mechanism of the patient to be treated should not be triggered by the compounds used. This can be realized by either immobilizing the biological compounds on a solid phase, or by a physical separation between the compounds and the blood (e.g., by membranes). The former method seems more favorable since the efficiency will be optimal. The problems encountered, however, are numerous.

Blood Component Removal↗

The role of blood component removal in essential and reactive thrombocytosis.

An elevated platelet count is now a common finding in both hospitalized and ambulatory patients with the advent of automated complete blood cell counters. Clinicians may be called upon to make a distinction between a reactive process and a primary hematologic disorder as the cause of a thrombocytosis and to determine whether treatment is indicated. Essential thrombocythemia and other myeloproliferative disorders may present with marked increases in the platelet counts and may be associated with thrombohemorrhagic complications. Reactive thrombocytosis can be caused by iron deficiency and a variety of inflammatory conditions, infections, malignancy, bleeding or hemolysis, splenectomy, and drugs. Acute therapy for all of these disorders has included blood component removal, specifically plateletpheresis. The role of plateletpheresis in current management of thrombocytosis is considered, based on current knowledge of pathophysiology and a review of the literature.

Female↗

Removal of blood components from cervical smears: implications for cancer diagnosis using FTIR spectroscopy.

Red and white cell lysis buffers were investigated to determine their ability to remove blood components from cervical smears prior to IR microspectroscopy. A white cell lysis buffer was effective in increasing the spectral reproducibility and sample homogeneity and in reducing the presence of inflammatory exudate, particularly leukocytes, from cervical smears. The reduction of leukocytes appeared to cause abnormal samples to be grouped with normal samples, resulting in poor discrimination. Despite differences between the cytological and histological diagnoses of cervical abnormalities, the results indicate that the differences seen in the spectra of exfoliated malignant and nonmalignant cervical cells could be due to the presence of inflammation.

Blood Cells↗

[Why remove leukocytes from labile blood products in 1995?].

During the last 15 years, the techniques to prepare leukocyte-poor cellular blood components greatly improved, as well as our knowledge about the role of leukocytes in many adverse effects of transfusion. These two facts favor the extension of indication of leukocyte-poor blood components. Leukocytes in blood components may be detrimental to their storage, due to their metabolic needs and to their progressive lysis, leading to the release of cytokines. Leukocytes are the exclusive vector in blood of CMV and HTLV viruses. Leukocytes are a key element of the immune modifications induced by transfusion. HLA alloimmunization is favored by the transfusion of large quantities of leukocytes HLA different from the recipient whose immune functions are intact. Conversely, the risk of transfusion associated graft versus host disease is dependent of the transfusion of mature T lymphocytes sharing a partial identity with the recipient, and/or an immune deficient status of the recipient. Between these two extremes, many other effects related to the presence of leukocytes in cellular blood components, as are the transfusion effect observed in transplant recipients, the increased risk for bacterial infection after transfusion, the increased risk for tumor recurrence or the reactivation of virus infections, remain to be fully understood. Despite recent significant improvements, further studies, experimental as well as clinical, will be needed to expand the indications of leukocyte-poor blood components.

Bacterial Infections↗

An overview of the rationale, process, and nursing implications of peripheral blood stem cell transplantation.

Peripheral blood stem cell transplantation (PBSCT) is the process of removing circulating stem cells from the peripheral blood through apheresis and returning these cells to the patient after dose-intensive chemotherapy. Clinical trials using PBSCT and dose-intensive chemotherapy are underway at cancer centers across the country. Nurses caring for patients who are undergoing PBSCT need an understanding of all aspects of the process in order to competently manage the toxicities, as well as to educate patients, families, and other staff. Nurses need to consider issues for nursing research to improve the quality of life for these patients.

Antineoplastic Agents↗

Update on pathogen reduction technology for therapeutic plasma: an overview.

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

Blood Component Removal↗

Bacterial contamination of blood products: factors, options, and insights.

Transfusion of bacterially contaminated blood products remains an overlooked problem. However, the risk of receiving a bacterially contaminated unit is greater than the combined risk of HIV-1/2, HCV, HBV, and HTLV I/II [American Association of Blood Banks Bulletin, no. 294, 1996]. Topics covered in this article include: the current incidence, clinical presentation and outcome, effective methods of detection, and ways to reduce bacterial contamination of blood products. There is no one existing strategy that can completely eliminate the risk of bacterial contamination. It is inevitable that partial solutions or combinations of methods will be implemented in the near future.

Bacteremia↗

Apheresis for severe malaria complicated by cerebral malaria, acute respiratory distress syndrome, acute renal failure, and disseminated intravascular coagulation.

Malaria has become a very uncommon disease in Italy. Recently a variety of circumstances, such as travel to tropical countries as well as immigration from Asia and Africa, have combined to increase the number of malaria cases recorded annually. In this report we describe the use of red cell exchange transfusion and plasma exchange in the treatment of a patient with hyperparasitemic malaria (51% erythrocytes or more parasitized). When first observed the patient was in shock and had signs of cerebral malaria, disseminated intravascular coagulation, and acute respiratory distress syndrome, which in the following 2 days were complicated by acute renal failure. After mefloquine therapy combined with 3 red blood cell exchanges, 2 plasma exchanges, and 10 dialysis sessions over 14 days, the patient recovered completely. This case of severe malaria with multiple complications, treated with mefloquine in conjunction with both exchange transfusion and plasmapheresis, had a successful outcome and lends further support to the possible beneficial role of exchange transfusion in complicated malaria.

Acute Disease↗

Is blood or bone marrow better?

Hematopoiesis that has been ablated with high-dose radiation-chemotherapy can be restored with either autologous peripheral stem cell transplantation (PSCT) or autologous bone marrow transplantation (ABMT). Characteristics unique to either type of transplant make one preferable to the other in certain clinical situations. When marrow metastases preclude ABMT, blood provides a suitable source of precursors for autografting. Peripheral cells are more time consuming to collect and more labor intensive to process and store. The peripheral autograft product can be manipulated with mobilization techniques (chemotherapy and/or cytokines) to provide more rapid recovery of granulocytes and perhaps red cells and platelets, while transplantation of manipulated marrow autografts has not yet been reported. Further advances in both ABMT and PSCT will provide additional opportunities to improve the outcome of patients treated with high-dose therapy.

Antineoplastic Agents↗

[Report on Notifications pursuant to Section 21 German Transfusion Act for 2001 and 2002].

The report pursuant to Section 21 German Transfusion Act is based on data referring to 4.53 and 4.66 million allogeneous whole blood donations and 1.35 and 1.89 million apheresis donations respectively for the years 2001 and 2002. Since 2000, the quantity of plasma for fractionation from apheresis has doubled to approx. 1 million litres in 2002. At the same time, the number of private apheresis facilities has also increased. The data on plasma for fractionation (both from whole blood and from apheresis) have shown a sharp increase for both report periods, mainly due to the rise in the quantity of plasma from apheresis. In spite of this, the quantity for plasma for fractionation available to the German market declined by 43% during the report period, due to increasing export figures. The data on the manufacture of blood components are reliable, since the notifications are almost complete. In 2001, 4.32 million transfusion units of erythrocyte concentrates, the most important product derived from whole blood donations, were manufactured, compared with 4.45 million in 2002, out of these, slightly less than 77 percent were manufactured in the blood donations services of the Red Cross. The consumption values reported were clearly below the figures for the manufacture, with 3.2 million transfusion units in 2001 and 3.5 million in 2002. However, some facilities of the health service did not meet the requirement to notify their figures. As far as the data on manufacture, imports and exports of plasma derivatives are concerned, further improvements are required because of the complexity of the matter and the various implications to be taken into account. However, a statement on the supply situation cannot be yet made anyway, due to the missing notifications on the consumption figures.

Blood Component Removal↗

Neocyte transfusion: a current perspective.

The most important studies published to date concerning the methods of preparation and the clinical utility of young red blood cells are reviewed 20 years after the first discoveries were made in this field. The results of each of the seven methods utilized (cells separators, cell washers, manual methods, etc.) are analyzed and the author's opinion is given concerning the results of in vitro and in vivo application. With few exceptions, the reviewed studies were done using small numbers of individuals. The majority of the studies confirm that it is possible to obtain YRBC enriched units. They also agree that YRBC have a higher survival rate in vivo than do normal RBC. In contrast, many of the wider-based studies did not show positive results when YRBC were used in patients or the results were too weak to justify the large amount of time and money these methods demand. Based on the review of all of the investigations published to date, there is little evidence to sustain the assumption of the clinical utility of YRBC used for multitransfused patients.

Blood Component Removal↗

Preparation of random donor leukocyte-poor platelets by cytapheresis.

Platelet refractoriness in treatment of multitransfused patients with haematologic malignancies can be delayed or prevented by transfusing leukocyte-poor platelet concentrates. Absence of consensus about the number of residual leukocytes that leads to a delay or prevention of HLA-antibody formation, may be based on a lack of sampling for determination of leukocyte contamination levels in platelet concentrates. From data presented in this study we conclude that if every preparation of platelets is also tested for platelet count, it reduces costs when the pheresis platelets can be split. Transfusion of platelets in patients can also be better evaluated.

Blood Component Removal↗

Platelet concentrates from buffy coats: improved conditions for preparation and evaluation in routine clinical use.

Since 1990, platelet concentrates prepared by soft centrifugation of buffy-coat pools diluted with a glucose-free, commercially available crystalloid solution (BC-PC) are the first choice product for all platelet recipients in our institution. Numerous in vitro and in vivo observations from our own and other laboratories indicate that BC-PC compare favorably to PC prepared from platelet-rich plasma (PRP). In the present in vitro study we evaluated traditional and bottom-and-top bags and modified centrifugation conditions with the aim of increasing in vitro platelet yield in BC-PC. This was 14-18% higher compared with our previous protocol when prolonged centrifugation and bottom-and-top bags were used. In addition, we evaluated post-transfusion platelet count increments in 42 unselected adult hematological patients routinely transfused with 703 1-5 day-old BC-PC pools. Transfusion data were managed with PLATELET, an MS-DOS compatible program which includes automated calculation of transfusion efficacy and periodic patient reports. Mean pre-, 1 h and 24 h post-transfusion platelet counts were 16, 38 and 28x10 9/L, respectively. Mean 1 h and 24 h post-transfusion platelet count increments, expressed as percentage of expected, were 40 and 24%, respectively. These data were similar to those obtained previously in 189 unselected hematological patients given 2432 PRP-PC transfusions (mean 1 h post-transfusion increment 46% of expected). The present in vitro study confirms that similar platelet yields can be obtained with the BC and PRP methods. In vivo findings show that also in routine conditions post-transfusion increments of PRP-PC and BC-PC are similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗