Blood safety and availability is an important public health matter. While substantial work is ongoing to identify replacement therapies and minimize the use of blood, transfusion services remain a critical component of the health-care system. Blood transfusion can be required in a number of frequently occurring clinical situations: major surgical procedures, including treatment of trauma patients; obstetric care with major bleeding during childbirth; and treatment of several medical diseases, especially hematological conditions. This article aims to outline essential safety aspects of blood transfusion services, starting with the proper selection of the unpaid blood donor to processing and appropriate testing of the collected blood unit as well as safety aspects of transfusion therapy, which include the appropriate clinical use of blood and blood components. The importance of accurate reporting of any incidents or adverse reactions to blood transfusion, which form the basis for a hemovigilance system, is briefly reviewed.

1 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden 2 Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark 3 Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden 4 Department of Clinical Immunology, Odense University Hospital, Odense, Denmark 5 Department of Medicine, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden 6 Department of Clinical Immunology, Århus University Hospital, Århus, Denmark. 7 Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA 8 Division of Cancer Control and Population Sciences, National Cancer Institute, NIH, Bethesda, Maryland, USA

Blood transfusion services are an important part of the health-care system since blood transfusion is required in a number of frequently occurring clinical situations: Major surgical procedures, including treatment of trauma patients; obstetric care with major bleeding during child birth; and treatment of several medical diseases, especially hematological diseases. This article outlines the essential safety aspects of blood transfusion from the proper selection of the unpaid blood donor to processing and appropriate testing of the blood unit to safety aspects of transfusion, which include the appropriate clinical use of blood and blood components. The importance of accurate reporting of any adverse reactions to blood transfusion, which form the basis for a hemovigilance system, is reviewed.

BACKGROUND Blood transfusions may influence the recipients' cancer risks both through transmission of biologic agents and by modulation of the immune system. However, cancer occurrence in transfusion recipients remains poorly characterized. METHODS We used computerized files from Scandinavian blood banks to identify a cohort of 888,843 cancer-free recipients transfused after 1968. The recipients were followed from first registered transfusion until the date of death, emigration, cancer diagnosis, or December 31, 2002, whichever came first. Relative risks were expressed as ratios of the observed to the expected numbers of cancers, that is, standardized incidence ratios (SIRs), using incidence rates for the general Danish and Swedish populations as a reference. All statistical tests were two-sided. RESULTS During 5,652,918 person-years of follow-up, 80,990 cancers occurred in the transfusion recipients, corresponding to a SIR of 1.45 (95% confidence interval [CI] = 1.44 to 1.46). The SIR for cancer overall decreased from 5.36 (95% CI = 5.29 to 5.43) during the first 6 months after transfusion to 1.10 or less for follow-up periods more than 2 years after the transfusion. However, the standardized incidence ratios for cancers of the tongue, mouth, pharynx, esophagus, liver, and respiratory and urinary tracts and for squamous cell skin carcinoma remained elevated beyond 10 years after the transfusion. CONCLUSIONS The marked increase in cancer risk shortly after a blood transfusion may reflect the presence of undiagnosed occult cancers with symptoms that necessitated the blood transfusion. The continued increased risk of tobacco- and alcohol-related cancers suggests that lifestyle and other risk factors related to conditions prompting transfusion rather than transfusion-related exposures per se are important to the observed cancer occurrence in the recipients.

Background Although mechanisms for detection of short-term complications after blood transfusions are well developed, complications with delayed onset, notably transmission of chronic diseases such as cancer, have been difficult to assess. Our aim was to investigate the possible risk of cancer transmission from blood donors to recipients through blood transfusion.Methods We did a register-based retrospective cohort study of cancer incidence among patients who received blood from donors deemed to have a subclinical cancer at the time of donation. These precancerous donors were diagnosed with a cancer within 5 years of the donation. Data from all computerised blood bank registers in Sweden and Denmark gathered between 1968 and 2002 were merged into a common database. Demographic and medical data, including mortality and cancer incidence, were ascertained through linkages with nationwide, and essentially complete, population and health-care registers. The risk of cancer in exposed recipients relative to that in recipients who received blood from non-cancerous donors was estimated with multivariate Poisson regression, adjusting for potential confounding factors.Findings Of the 354094 transfusion recipients eligible for this analysis, 12012 (3%) were exposed to blood products from precancerous donors. There was no excess risk of cancer overall (adjusted relative risk 1.00, 95% CI 0.94-1.07) or in crude anatomical subsites among recipients of blood from precancerous donors compared with recipients of blood from non-cancerous donors.Interpretation Our data provide no evidence that blood transfusions from precancerous blood donors are associated with increased risk of cancer among recipients compared with transfusions from non-cancerous donors.

BACKGROUND:Transfusion safety rests heavily on the health of blood donors. Although they are perceived as being healthier than average, little is known about their long-term disease patterns and to which extent the blood banks' continuous efforts to optimize donor selection has resulted in improvements. Mortality and cancer incidence among blood donors in Sweden and Denmark was investigated. STUDY DESIGN AND METHODS:All computerized blood bank databases were compiled into one database, which was linked to national population and health data registers. With a retrospective cohort study design, 1,110,329 blood donors were followed for up to 35 years from first computer-registered blood donation to death, emigration, or December 31, 2002. Standardized mortality and incidence ratios expressed relative risk of death and cancer comparing blood donors to the general population. RESULTS:Blood donors had an overall mortality 30 percent lower (99% confidence interval [CI] 29%-31%) and cancer incidence 4 percent lower (99% CI 2%-5%) than the background population. Mortality rates and cancer incidence were lowest for outcomes that are recognized as being related to lifestyle factors such as smoking or to the selection criteria for blood donation. Blood donors recruited in more recent years exhibited a lower relative mortality than those who started earlier. CONCLUSION:Blood donors enjoy better than average health. Explicit and informal requirements for blood donation in Scandinavia, although mostly of a simple nature, have successfully refined the selection of a particularly healthy subpopulation.

This study describes a new approach to the determination of all known mannan-binding lectin (MBL) mutations. The distribution of known variants of the MBL gene in a population of healthy unrelated Danes was determined and the genotype was correlated with the plasma MBL concentrations. The following genetic polymorphisms were studied: three point mutations in the promoter region at position −550 (H/L variants), −221 (X/Y variants), −70 (nt C or T), one point mutation in the 5′ untranslated (UT) region at position +4 (P/Q variants) and three point mutations located at codons 52, 54 and 57 in exon 1 of the MBL gene, at nucleotide positions 223, 230 and 239, respectively. To perform genotyping, we designed sequence specific primers for a polymerase chain reaction (PCR–SSP). PCR–SSP is a powerful technique for the discrimination of alleles resulting from single base substitutions and is a widely used technique. Another major advantage of the PCR–SSP method is its ability to determine whether sequence motifs are in cis or trans. The frequencies of variants in exon 1 obtained by PCR–SSP were completely comparable to results obtained by previously described PCR methods, restriction fragment length polymorphism (RFLP) and site-directed mutagenesis (SDM). This PCR–SSP method is performed with standard laboratory equipment and has the capacity to detect all genetic variants in 100 samples in 2 days at an estimated total cost of GBP 11 per sample. Analysing the correlation between MBL haplotype and plasma MBL levels, we confirmed that three different structural variants, B, C and D and the promoter haplotypes HY, LY and LX have a dominant effect on the concentration of MBL. The HY haplotype is associated with the highest plasma concentration, the LY haplotype with intermediate levels and the LX haplotype with the lowest levels. The LX haplotype was found to be associated with very low levels of MBL similar to those found in association with the structural B genotype. The gene frequencies of variants in the MBL gene in the Danish population studied correspond to previous reports on Caucasian populations.

TransfusionVolume 40, Issue 4 p. 491-492 Nomenclature of granulocyte alloantigens Rudi Steffensen MT, Rudi Steffensen MT Regional Center for Blood Transfusion and Clinical Immunology, Aalborg Hospital, Reberbansgade, DK-9100 Aalborg, Denmark, e-mail: rudi@aas.nja.dkSearch for more papers by this authorKim Varming MD, Kim Varming MD Regional Center for Blood Transfusion and Clinical Immunology, Aalborg Hospital, Reberbansgade, DK-9100 Aalborg, Denmark, e-mail: rudi@aas.nja.dkSearch for more papers by this authorCasper Jersild MD, Casper Jersild MD Regional Center for Blood Transfusion and Clinical Immunology, Aalborg Hospital, Reberbansgade, DK-9100 Aalborg, Denmark, e-mail: rudi@aas.nja.dkSearch for more papers by this author Rudi Steffensen MT, Rudi Steffensen MT Regional Center for Blood Transfusion and Clinical Immunology, Aalborg Hospital, Reberbansgade, DK-9100 Aalborg, Denmark, e-mail: rudi@aas.nja.dkSearch for more papers by this authorKim Varming MD, Kim Varming MD Regional Center for Blood Transfusion and Clinical Immunology, Aalborg Hospital, Reberbansgade, DK-9100 Aalborg, Denmark, e-mail: rudi@aas.nja.dkSearch for more papers by this authorCasper Jersild MD, Casper Jersild MD Regional Center for Blood Transfusion and Clinical Immunology, Aalborg Hospital, Reberbansgade, DK-9100 Aalborg, Denmark, e-mail: rudi@aas.nja.dkSearch for more papers by this author First published: 24 April 2002 https://doi.org/10.1046/j.1537-2995.2000.40040491.xCitations: 8Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume40, Issue4April 2000Pages 491-492 RelatedInformation

To gain further insight into the effects of major vascular surgery involving the abdominal aorta on complement and leukocytes, serial measurements of leukocyte and differential counts, plasma concentrations of Cad, and granulocyte elastase bound to α1 proteinase inhibitor (E-α1PI) were made after aorta declamping in a group of patients not receiving blood or plasma. In the hours after declamping, lymphocyte count decreased, whereas an increase was noticed in leukocytes, neutrophils, and plasma E-α1Pl. Complement activation was not found. Previous reports on complement activation during aortic surgery probably reflect the administration of blood and plasma during the surgical procedures. Whether aortic cross-clamping or interaction between granulocytes and the aortic prothesis is responsible for the release of lysosomal enzymes during the procedure warrants further studies.

In an effort to further elucidate the complex changes in the complement-leukocyte system during cardiopulmonary bypass (CPB), plasma levels of C3d, C5a, and granulocyte elastase bound to alpha1-proteinase inhibitor (E-alpha1 PI) were followed prior to, during, and after CPB. Leukocyte and differential cell counts and granulocyte migration were also determined. Complement activation was documented during CPB by an increase in plasma C3d corrected for hemodilution. Significant amounts of C5a were not revealed. Cell counts decreased during CPB but, if corrected for hemodilution, remained unchanged apart from a slight decrease in lymphocyte count after 60 minutes. Eighteen hours after CPB, neutrocytosis and lymphopenia occurred. Plasma E-alpha1 PI increased during CPB, reflecting release of granulocyte lysosomal enzymes. Granulocyte migration was transitorily depressed during CPB, and it was shown that this was due to the appearance of an intrinsic cellular defect. CPB is associated with acute changes in cells and plasma, resembling an acute whole-body inflammatory response, with transitory impairment of granulocyte migration. The clinical significance of these observations remains to be determined.

The Organon Teknika Vironostika anti-HTLV-III/LAV test was evaluated in three Danish blood banks. The evaluation comprised in total 3,940 consecutive donors. In all three blood banks the tests were carried out exactly according to the manufacturer's instructions, using a low cut-off value defined as (4N + P)/5, where N and P are means of optical densities of known negative and positive samples. By this method the overall frequency of repeatably positive samples was 0.30%. When tested by Western blot, however, none of these samples were shown to contain specific antibodies against HTLV-III/LAV proteins. When testing different categories of patients, only sera containing HLA antibodies gave rise to false-positive reactions. Finally, important differences in the results were observed regarding sample preparation, single or dual wavelength optical density readings, and the experience of the technical staff.

Differences in biocompatibility of various hemodialysis membranes cause different degrees of complement activation, leukopenia, and hypoxemia during hemodialysis. In order to further clarify the complex sequence of activation of complement, leukopenia and dialysis hypoxemia, we followed leukocyte count and arterial oxygen tension in 23 patients during two successive dialyses using membranes based on regenerated cellulose (RC) and cellulose acetate (CA). In 12 of the patients, signs of complement activation were investigated by following changes in arterial levels of total hemolytic complement, plasma C3d and C5a. Furthermore, C5a was determined in plasma from the dialyzer effluent line. The study demonstrates basic differences in biocompatibility of the two membranes: hemodialysis using RC membranes was associated with more pronounced leukopenia and hypoxemia than dialysis with CA membranes and, during dialysis using RC membranes, generation of C5a in the dialyzer was evident by demonstration of high values of this anaphylatoxin in dialyzer effluent plasma at the beginning of treatment with gradual decline towards detection limit at the end. Plasma C3d in arterial blood rose during dialyses with both RC and CA membranes, but significantly more with RC, suggesting that accumulation of this complement fraction may serve as a sensitive parameter for complement activation during hemodialysis.Our results suggest a pivotal role of C5a for hemodialysis-induced leukopenia and show that activation of complement, leukopenia, and arterial hypoxemia are interlinked membrane-dependent events.