It is generally assumed that febrile nonhemolytic transfusion reactions are an immunologically mediated reaction involving the recipient's plasma and the white cells in the donor unit. This has led to the use of white cell reduction and pretransfusion medication, to try to minimize these reactions. To better understand febrile transfusion reactions, a prospective study was performed in which all patients receiving platelet and red cell transfusions in a tertiary-care medical center were interviewed before and after transfusion to obtain information about the typical presentation of the syndrome. It was found that transfusion reactions were much more frequently associated with platelet transfusion (30.8%) than with red cell transfusion (6.8%, p < 0.0005). The routine use of antipyretics prevented most episodes of fever but did not prevent the occurrence of other symptoms such as chills, cold, and discomfort. The application of logistic regression analysis revealed that the dominant factor determining the risk of a reaction was not white cell contamination, but the age of the component (p < 0.005). The significant relationship between reaction and the increasing age of the component suggests that cytokines released in the component during storage may be responsible for many reactions to blood components.

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.

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Background Over the past 20 years there have been more than 20 randomized controlled trials (RCTs) that have investigated various aspects of platelet transfusion therapy in haematology ⁄ oncology patients. These studies have focused on the best platelet product, the importance of ABO compatibility, pathogen inactivation of platelets, platelet triggers and the optimal platelet dose. Aims This article summarizes current evidence to support the timing and dosing of platelet transfusions and to explore some ideas of where clinical research in this area may be heading. Materials and MethodsThe articles reviewed in this presentation were identified through a search of PubMed using the term, platelet transfusion and setting limits to identify clinical studies, human studies and manuscripts in English. Results and Discussion Three RCTs have informed practices around platelet transfusion trigger with the largest study by Rebulla et al., being the primary study that has changed practices worldwide, with a move towards a lower prophylactic platelet transfusion trigger of 10 · 10 9 ⁄ l. Two groups (Germany and Oxford, UK) are currently investigating whether we can push the boundaries of prophylactic platelet transfusions even further by eliminating this form of therapy. Preliminary results from these studies have been published but we will await the final results to determine whether this research will indeed change practice. Over the past year there has also been two major studies (one by the BEST Collaborative, and the second by the US Transfusion Medicine ⁄ Hemostasis Network), that provide new information to guide platelet dosing. The Study by the BEST Collaborative (SToP) compared low dose platelets to standard dose platelets with WHO bleeding greater than or equal to Grade 2 as the primary outcome. The US study (PLADO) compared three doses (low, medium and high) and measured the same outcome (WHO bleeding ‡ Grade 2). Conclusions Although all of these studies further our knowledge to prescribe platelet transfusions, they also raise some interesting questions about the clinical relevance of the outcomes that we are currently using for these studies. The trend over the past decade has been to use bleeding as the primary outcome; however, bleeding is a complex composite outcome (Grades 2, 3 and 4) comprised of some surrogate components (Grades 2 and 3). It is also an outcome that may be difficult to measure and grade in a consistent and reliable manner. The clinical relevance of this outcome is also complex and may vary depending on the perspective from which it is viewed.

Typically the serological diagnosis of alloimmune haemolytic disease of the newborn (HDN) includes a positive direct antiglobulin test on the infant's red cells, and the presence of an IgG red cell alloantibody in both maternal and cord sera. HDN with a negative direct antiglobulin test has been reported with anti-A and anti-B, but not with other red-cell alloantibodies. In this report we describe four examples of HDN in infants whose red cells had a negative direct antiglobulin test. The first case was diagnosed retrospectively when the infant was admitted to hospital aged 3 weeks with severe anaemia and cardiac failure, and subsequently died. Maternal and infant sera were both shown to contain anti-C: however, the direct antiglobulin test on the infant's red cells was negative. Approximately 1 year later the mother of this infant gave birth to triplets: soon after birth one of the triplets required an exchange transfusion, one had hyperbilirubinaemia, and the third was unaffected. Anti-C and anti-e were detectable in the maternal serum at this time. The most probable Rh genotypes of the two affected infants were R1R2 (CDe/cDE), while the Rh genotype of the unaffected infant was R2R2 (cDE/cDE). Anti-c was implicated as causing HDN in a fourth infant (from a different family) who was a hydropic stillborn. The direct antiglobulin test on fetal blood was negative and other causes of non-immune hydrops were excluded. These four infants provide evidence that the direct antiglobulin test may be negative in some severely affected and even fatal cases of HDN.