The low prevalence Rh antigen Be(a) (Rh36) is associated with RHCE*ce 662C>G in exon 5, which is predicted to encode Rhce 221Arg.

BACKGROUND AND OBJECTIVES: The low prevalence antigen, Be(a), is produced by a complex that also produces weak c, e and f (ce). We report here the molecular basis associated with Be(a) antigen expression. MATERIALS AND METHODS: Peripheral blood samples from four Be(a+) probands were tested. Haemagglutination, gDNA extraction, PCR-based assays, reticulocyte RNA isolation, Rh-cDNA analyses, and sequencing were performed by standard procedures. RESULTS: RBCs from Probands 1 and 3 were D-C-E-c+e+, and from Probands 2 and 4 were D+C+E-c+(W)e+. In proband 1, cDNA sequencing of RHCE revealed heterozygosity of nucleotide (nt) 662C/G in exon 5 of RHCE*ce. No other nucleotide changes were observed. As the 662C>G nucleotide change ablates a MscI restriction enzyme cleavage site, PCR-RFLP analysis was performed and the RHCE*ce nt 662C/G heterozygosity was detected on gDNA from the four probands and two children from both Proband 3 and Proband 4. CONCLUSION: The low prevalence Rh antigen, Be(a), is associated with a single nucleotide change in exon 5 of RHCE*ce; that of 662C>G and this change is predicted to alter proline at amino acid position 221 of Rhce to arginine. The fundamental differences in the properties of these two amino acids may impose a steric and/or charge-related effect on the protein, and thereby provide an explanation for the weakened expression of c, e and f (ce) antigens in the Be(a) phenotype.

The evidence for the use of recombinant factor VIIa in massive bleeding: development of a transfusion policy framework.

A review of the recent randomized control trial evidence of the use of recombinant factor VIIa (rFVIIa) in massive bleeding. rFVIIa is a recombinant genetically engineered clotting factor that has been used for the management of haemophilia patients with inhibitors. There has been increasing use in patients with massive bleeding, even when there is no underlying coagulation disorder present. In November 2006, the Canadian National Advisory Committee on Blood and Blood Products engaged in a consultation and review process with several leading Canadian experts to review and discuss the current evidence up to November 2006. There is little evidence to support the routine use of rFVIIa in massive bleeding on review of 13 randomized controlled trials. rFVIIa should only be considered as part of a transfusion policy framework for massive bleeding after all other transfusion and supportive measures are considered. An example of a policy framework is presented.

Epstein-Barr virus polymorphic B-cell lymphoma associated with leukemia and with congenital immunodeficiencies.

Polymorphic B-cell lymphoma seen in four patients with congenital immunodeficiencies and in two patients with leukemia receiving chemotherapy was associated with the Epstein-Barr virus (EBV). The tumors had characteristic histologic features: they were polymorphic consisting of a mixture of lymphoblasts and differentiated cells including plasma cells, and areas of hemorrhagic necrosis were prominent. The tumors were either polyclonal, monoclonal, or multiclonal. Patients with congenital immunodeficiencies who developed these tumors died despite radiotherapy, corticosteroids plus acyclovir, or a combination of intravenous (IV) immunoglobulins and alpha 2 interferon. Patients with leukemia recovered when immunosuppressive drugs were discontinued and leukemia has not recurred over a period of 2 and 4 years, respectively, in the two patients.

Platelet transfusion for patients with cancer: clinical practice guidelines of the American Society of Clinical Oncology.

OBJECTIVE: To determine the most effective, evidence-based approach to the use of platelet transfusions in patients with cancer. OUTCOMES: Outcomes of interest included prevention of morbidity and mortality from hemorrhage, effects on survival, quality of life, toxicity reduction, and cost-effectiveness. EVIDENCE: A complete MedLine search was performed of the past 20 years of the medical literature. Keywords included platelet transfusion, alloimmunization, hemorrhage, threshold and thrombocytopenia. The search was broadened by articles from the bibliographies of selected articles. VALUES: Levels of evidence and guideline grades were rated by a standard process. More weight was given to studies that tested a hypothesis directly related to one of the primary outcomes in a randomized design. BENEFITS/HARMS/COST: The possible consequences of different approaches to the use of platelet transfusion were considered in evaluating a preference for one or another technique producing similar outcomes. Cost alone was not a determining factor. RECOMMENDATIONS: Appendix A summarizes the recommendations concerning the choice of particular platelet preparations, the use of prophylactic platelet transfusions, indications for transfusion in selected clinical situations, and the diagnosis, prevention, and management of refractoriness to platelet transfusion. VALIDATION: Five outside reviewers, the ASCO Health Services Research Committee, and the ASCO Board reviewed this document. SPONSOR: American Society of Clinical Oncology

National survey of neonatal transfusion practices: II. Blood component therapy.

Neonatal transfusion practices during 1989 of 452 institutions involved in transfusing infants were surveyed by questionnaire. Most respondents (77%) transfused fresh frozen plasma appropriately (ie, primarily to treat coagulation disorders). However, 11% stated that their most frequent use of fresh frozen plasma was solely to treat hypovolemia, a practice generally not recommended. Seventy-eight percent of respondents transfused platelets to treat bleeding infants with blood platelet counts of less than 50 x 10(9)/L; 84% gave platelets to sick, premature neonates with counts of less than 50 x 10(9)/L whether or not bleeding was evident. Only 35% of respondents transfused granulocytes for neonatal sepsis; most institutions used buffy coats isolated from units of blood--a product readily available, but of questionable efficacy when compared with leukapheresis granulocytes. Ninety-three percent of respondents provided blood components with low risk of transmitting cytomegalovirus: components from seronegative donors were used by 84%, leukocyte-reduced products by 6%, and a combination by 10%. Thirteen percent of respondents gave gamma-irradiated blood components to all and 46% gave them to some neonates to prevent graft vs host disease. Forty-one percent did not routinely irradiate. Ten percent of respondents used leukocyte reduction instead of gamma irradiation to prevent graft vs host disease, a practice currently not advocated. Thus, national transfusion practices for neonates are variable, controversial, and, occasionally, other than those usually recommended. Additional research and educational efforts are needed to ensure optimal transfusion therapy.

National survey of neonatal transfusion practices: I. Red blood cell therapy.

Neonatal blood component transfusion practices during 1989 were surveyed via a questionnaire developed by the Pediatric Hemotherapy Committee of the American Association of Blood Banks. Of 1790 questionnaires mailed, 452 were selected to form the database for this analysis because they were from institutions in which neonates were transfused. Nearly all institutions contained intensive care units directed by neonatologists and were involved in the management of high-risk infants. Results from institutions serving as the primary pediatric teaching hospital of a medical school were compared with those with no medical school affiliation. Thirty-six percent of primary pediatric teaching hospitals and 52% of hospitals with no medical school affiliation performed pretransfusion testing in excess of that required, resulting in additional blood loss in neonates. Sixty-six percent of primary pediatric teaching hospitals used fresh frozen plasma to adjust the hematocrit of red blood cell concentrates prior to transfusion (a practice increasing donor exposure), compared with only 29% of hospitals with no medical school affiliation. The usual indication for small-volume red blood cell transfusions in severely ill neonates was to maintain a desired hematocrit level, whereas for stable infants, red blood cell transfusions were given to treat symptomatic anemia, rather than to maintain a predetermined hematocrit. As found in 1985, neonatal transfusion practices in 1989 were variable. However, improvements have occurred since 1985 to suggest that further research and educational efforts may serve to promote even better neonatal transfusion therapy.

Red blood cell transfusions for preterm infants: the role of evidence-based medicine.

Increasingly clinicians attempt to base decisions regarding patient management on the results of clinical studies in addition to expert opinion and their own practical experience. In this article, the author reviews the published studies available to assist clinicians to make evidence-based decisions in three topics related to small volume red blood cell (RBC) transfusions for preterm infants; namely, studies examining the effects of RBC transfusions on possible symptoms of anemia such as tachypnea, apnea or other cardiorespiratory irregularities, studies investigating the collection and transfusion of umbilical cord blood and finally studies addressing the duration of storage and use of additive solutions for RBCs for transfusion to neonates. Based on the review of these studies, guidelines for small volume RBC transfusions in preterm infants are suggested.

Multiple small bowel perforations in leukemia secondary to Epstein-Barr virus lymphoma with survival: a case report.

This is the case report of a 4-year-old white boy who was diagnosed as having acute lymphoblastic leukemia (ALL) in November 1985. While in remission and on maintenance chemotherapy, he developed a primary Epstein-Barr virus (EBV) respiratory infection in October 1986. On October 27, 1986 a plain abdominal radiograph taken for abdominal distention showed free air. At celiotomy, multiple nodules were noted to stud the small bowel. Central necrosis of these nodules with perforations were present in the distal small bowel. Resections and end-to-end anastomoses were performed. Three days later the patient again had a similar acute abdominal episode. At reexploration, similar lesions in the liver, kidney, duodenum, proximal jejunum, and colon were found. Liver biopsy as well as intestinal resections and end-to-end anastomoses were performed, along with a loop ileostomy. Polymorphic B-cell lymphoma positive for EBV was found in the specimens. After cessation of chemotherapy and institution of abdominal radiotherapy, the hepatic and renal lesions were seen to resolve on computed tomography scan. The patient's course was complicated by the development of cervical and mediastinal abscesses that were drained, and E coli sepsis accompanied by chronic diarrhea requiring intravenous hyperalimentation. By January 1988, he appeared to be recovering. His ileostomy was closed in March 1988. Despite cessation of chemotherapy since October 1986, the patient is now well and in complete remission.

Transfusion associated graft-versus-host disease, cytomegalovirus infection and HLA alloimmunization in neonatal and pediatric patients.

Modern transfusion support of pediatric patients requires attention to the necessity to provide specialized or modified blood components to these patients who are often immunocompromised and/or affected by very complex medical and surgical illnesses. In this review we will address three potential complications of transfusion that may require specialized components for their prevention in selected patients namely transfusion-associated graft-versus-host disease, transfusion-transmitted cytomegalovirus infection and HLA alloimmunization, with particular reference to the indications for prevention of these transfusion complications in neonatal and pediatric patients.

Reaction rates in allogeneic donors.

In Canada and several other countries, there is an upper age limit for blood donation. In order to evaluate the safety of whole blood donation in elderly Canadian allogeneic donors, we analysed reaction rates following whole blood donation. Reactions rates in allogeneic whole blood donors who donated at Canadian Blood Services were reviewed retrospectively. Rates were analysed by age, donation frequency and by donation frequency for each age group. A total of 5478 reactions were available for analysis in 469 837 donors. The highest rate of mild reactions occurred in donors less than 20 years of age. Moderate and severe reactions decreased with increasing age and with donation frequency. Age-adjusted rates for mild reactions were less frequent in donors aged 66-77 years than in donors younger than 20 years. Although age-adjusted moderate reactions varied with donation frequency, after seven donations, rates were not increased for donors aged 60 years or older (0.61% for donors aged less than 20 years compared to 0.03% for donors aged 60-65 years compared to 0% for donors aged 66-71 years). Age-adjusted rates for severe reactions generally did not increase with donation frequency. These results confirm the safety of whole blood donation in regular donors who are 66-71 years of age.

Commentary on the safety of red cells preserved in extended-storage media for neonatal transfusions.

Red cells preserved in extended-storage media are the standard product dispensed by many regional blood centers. When the red cells are intended for neonatal transfusion, concern exists about the safety of the relatively high quantities of additives present in these media. Definitive studies to address these concerns are not available. Therefore, to estimate the effects of additives and to delineate circumstances in which they might be harmful, the quantities transfused in defined clinical settings were calculated, and the following recommendations are offered for transfusing infants less than 4 months of age. First, red cells preserved in extended-storage media should present no substantive risks when used for small-volume (approximately 10 mL/kg) transfusions of premature infants and can be used without additional processing. Second, the risks of the most premature neonatal patients or those with severe renal and/or hepatic insufficiency cannot be defined clearly, and, because data are not available to ensure safety for these infants, removal of the additive medium and resuspension of the red cells in saline or albumin solution immediately before transfusion are recommended. Third, following a similar rationale, it seems prudent to avoid using entire units of red cells preserved in extended-storage media in massive transfusion settings (e.g., exchange transfusion, cardiac surgery, and extracorporeal membrane oxygenation). In these settings, the preservative medium should be removed and the red cells resuspended in the fluid that is most appropriate for the procedure that is planned. It must be emphasized that these recommendations are based on calculations and hypothetical settings, not actual data. Accordingly, they are tentative and should be altered as definitive information becomes available.

Evaluation of pediatric transfusion practice using criteria maps.

Pediatric blood transfusion practice in a tertiary-care pediatric hospital was evaluated retrospectively by using the technique of criteria mapping. A total of 630 transfusion episodes involving red cell concentrates, frozen plasma (plasma frozen within 24 hours of collection), platelet concentrates, and albumin were reviewed: 243 (86.2%) were reviewed only by a technical assistant, and 87 (13.8%) required additional physician review. Of these, 138 were red cell concentrate transfusions: 79.7 percent of that group were considered appropriate, 11.6 percent of unknown benefit/risk ratio, 5.8 percent inappropriate, and 2.9 percent impossible to evaluate. Some 246 frozen plasma transfusions were reviewed: 42.3 percent were considered appropriate, 32.5 percent of unknown benefit/risk ratio, 17.5 percent inappropriate, and 7.7 percent impossible to evaluate. A total of 139 platelet concentrate transfusions were reviewed: 64.7 percent were considered appropriate, 16.5 percent of unknown benefit/risk ratio, 10.1 percent inappropriate, and 8.6 percent impossible to evaluate. Some 107 albumin transfusions were reviewed: 90.6 percent were considered appropriate, 1.9 percent inappropriate, and 7.5 percent impossible to evaluate. The criteria maps developed for this study were easy for the technical assistant to use, and areas of appropriate and inappropriate pediatric transfusion practice were clearly identified.