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.

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.

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

Anomaly of the des-Arg9-bradykinin metabolism associated with severe hypotensive reactions during blood transfusions: a preliminary study.

BACKGROUND: Severe hypotensive reactions have been described after the transfusion of platelets or red cells through negatively-charged bedside white cell-reduction filters. The possibility of a role for bradykinin (BK) in the genesis of these reactions has been raised. STUDY DESIGN AND METHODS: To understand if an anomaly of BK metabolism is associated with these reactions, the metabolism of BK and des-Arg9-BK was studied in the sera of four patients who presented with a severe hypotensive transfusion reaction. Tests were performed in the absence and the presence of complete in vitro inhibition of angiotensin-converting enzyme (ACE) activity by enalaprilat. RESULTS: In the presence of ACE inhibition (enalaprilat), the half-life (t1/2) of BK measured in the sera of patients who presented with a severe hypotensive transfusion reaction (361 +/- 90 sec) was not significantly different from that measured in the sera of normal controls (249 +/- 16 sec). In the presence of ACE inhibition (enalaprilat), the t1/2 of des-Arg9-BK was significantly greater in patients who presented with a severe hypotensive transfusion reaction (1549 +/- 319 sec) than in normal controls (661 +/- 38 sec) (p < 0.001). CONCLUSION: A metabolic anomaly mainly affecting the degradation of des-Arg9-BK could be responsible for its accumulation in vivo. Des-Arg9-BK could be responsible, at least in part, for severe hypotensive transfusion reactions.

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.

Nationwide survey of home transfusion practices.

BACKGROUND: Limited information exists on home transfusion practices. STUDY DESIGN AND METHODS: In 1995, a survey requesting data for 1994 was sent to 1273 American Association of Blood Banks (AABB) institutional members and 113 non-AABB home health care agencies that provide out-of-hospital transfusions. RESULTS: Of 943 respondents, 102 provide blood to a home transfusion program, 37 provide blood and run a home transfusion program, and 13 run a home transfusion program only, for a total of 152 (16%) with some involvement in home blood transfusions. Most of the 50 respondents with a home transfusion program are licensed by their state and accredited by the Joint Commission on Accreditation of Healthcare Organizations. All respondents have written policies for home transfusion, and 90 percent require a signed informed-consent document before initiating transfusions in the home. Most have policies requiring that there be a second adult and a telephone in the home, that the home be deemed safe for transfusion, that the patient's physician be readily available, and that the patient have had prior transfusions. The most common component issued by the blood providers was red cells, followed by platelets. White cell-reduced components were always provided by 36 percent of respondents. The most common patient diagnosis was cancer. Home transfusions were provided primarily by registered nurses. Only 14 percent of respondents indicated that the medical director of the blood bank is responsible for approving a patient for home transfusion. A posttransfusion visit is performed by 46 percent of respondents. CONCLUSION: Although most facilities have policies for the administration of home transfusions, there remains marked heterogeneity among blood providers and transfusionists regarding home transfusion practices.

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.

A survey of Canadian neonatal blood transfusion practices.

In 1990, the Pediatric Hemotherapy Committee of the American Association of Blood Banks developed and distributed a questionnaire addressing neonatal blood transfusion practices. The same questionnaire was subsequently sent to Canadian university-affiliated hospitals (n = 92). This report describes the results of the Canadian survey. Seventy-two percent (n = 66) of institutions contacted responded. Of these 42% (n = 28) had sufficient experience with neonatal transfusions and provided sufficient data for analysis. Although the majority of stated practices did follow published guidelines, several areas of variability and/or suboptimal practices were identified. With respect to component selection and preparation, suboptimal practices included excessive pretransfusion testing, unnecessary routine washing of RBC concentrates for small-volume transfusions, routine volume reduction of platelet concentrates and the use of suboptimal granulocyte preparations. With respect to transfusion practices, a disturbingly high percentage of respondents indicated that frozen plasma would be given in situations generally considered inappropriate. There was a great deal of variability in the provision of blood components at low risk for CMV, in the use of gamma irradiation and in the platelet count used for prophylactic platelet transfusions. The data collected in this survey provide information concerning practices that require improvement, identify areas where further research is desirable and provide a basis for comparison with current and future neonatal blood transfusion practices.

Hypotensive reactions: a previously uncharacterized complication of platelet transfusion?

BACKGROUND: In 1993, the American Association of Blood Banks (AABB) received reports of severe hypotensive reactions associated with platelet transfusions. The question arose as to whether these reports were indicative of a previously uncharacterized platelet transfusion reaction. STUDY DESIGN AND METHODS: To further characterize these reactions, the AABB Transfusion Practices Committee developed a series of three questionnaires. The initial questionnaire was sent to all AABB institutional members; the two subsequent questionnaires were sent to those institutions reporting severe and/or unusual platelet transfusion reactions. This report focuses on the 24 responses to the third and most detailed questionnaire, which specifically addressed reactions that were characterized by hypotension and/or unexplained respiratory failure. RESULTS: Of the 24 detailed responses received, 4 were not considered to represent unusual reactions to platelet transfusion, 3 described reactions consistent with a (presumably unrecognized) diagnosis of transfusion-related acute lung injury, and 17 described reactions that were primarily characterized by hypotension. The majority of the hypotensive reactions occurred within 1 hour of the beginning of the transfusion (88%), were associated with respiratory distress (82%), and resolved rapidly after cessation of the transfusion (82%). Eighty-eight percent of implicated components had been white cell reduced by filtration. CONCLUSION: The hypotensive platelet transfusion reactions that were described appear to represent a previously uncharacterized complication of platelet transfusion. However, the nature of the questionnaires used in this investigation does not allow the drawing of firm conclusions as to the frequency or the cause of these reactions.

Transfusion practices in human immunodeficiency virus-infected patients.

BACKGROUND: The reported immunomodulatory effects of transfusion raise concern about the potential for virus activation and tumor growth in human immunodeficiency virus (HIV)-infected patients. In the absence of "standards" of transfusion practice for such patients, a survey of transfusion policies among institutions specializing in the care of HIV-infected patients was performed to delineate current practices. STUDY DESIGN AND METHODS: A survey developed by the Transfusion Practices Committee of the American Association of Blood Banks was sent to 47 AIDS clinical trial units and 14 regional hemophilia centers in North America. RESULTS: Forty-three percent of centers completed the survey. Most centers observed more than 200 HIV-infected patients each. The key findings were that 1) 81 percent of centers used identical red cell transfusion criteria for HIV-infected and noninfected patients; 2) 52 percent used recombinant human erythropoietin as initial treatment for zidovudine-induced anemia, while 46 percent used recombinant human erythropoietin for anemia not associated with zidovudine; 3) 35 percent of centers used white cell-reduced blood components in lieu of cytomegalovirus (CMV)-seronegative components when administering transfusion(s) to CMV-seronegative patients; 4) 27 percent gamma-radiated cellular components, but no case of graft-versus-host disease had been observed; 5) > 85 percent of centers used monoclonal factor VIII for pediatric and adult hemophiliacs infected with HIV; 6) approximately one-third of centers routinely white cell-reduced cellular components; and 7) the most common reasons for white cell reduction included reduction of febrile reactions and CMV risk, reduction of platelet alloimmunization, and delay of immunomodulatory consequences of transfusion. CONCLUSION: There is marked heterogeneity in transfusion practice for HIV-infected patients. Modification of cellular components to achieve different objectives is routine in many centers.