Low-Frequency Blood Group Antigens in Switzerland.

BACKGROUND: High-frequency blood group antigens (HFA) are present in >90% of the human population, according to some reports even in >99% of individuals. Therefore, patients lacking HFA may become challenging for transfusion support because compatible blood is hardly found, and if the patient carries alloantibodies, the cross-match will be positive with virtual every red cell unit tested. METHODS: In this study, we applied high-throughput blood group SNP genotyping on >37,000 Swiss blood donors, intending to identify homozygous carriers of low-frequency blood group antigens (LFA). RESULTS: 326 such individuals were identified and made available to transfusion specialists for future support of patients in need of rare blood products. CONCLUSION: Thorough comparison of minor allele frequencies using population genetics revealed heterogeneity of allele distributions among Swiss blood donors which may be explained by the topographical and cultural peculiarities of Switzerland. Moreover, geographically localized donor subpopulations are described which contain above-average numbers of individuals carrying rare blood group genotypes.

Red blood cell use in Switzerland: trends and demographic challenges.

BACKGROUND: Several studies have raised concerns that future demand for blood products may not be met. The ageing of the general population and the fact that a large proportion of blood products is transfused to elderly patients has been identified as an important driver of blood shortages. The aim of this study was to collect, for the first time, nationally representative data regarding blood donors and transfusion recipients in order to predict the future evolution of blood donations and red blood cell (RBC) use in Switzerland between 2014 and 2035. MATERIALS AND METHODS: Blood donor and transfusion recipient data, subdivided by the subjects' age and gender were obtained from Regional Blood Services and nine large, acute-care hospitals in various regions of Switzerland. Generalised additive regression models and time-series models with exponential smoothing were employed to estimate trends of whole blood donations and RBC transfusions. RESULTS: The trend models employed suggested that RBC demand could equal supply by 2018 and could eventually cause an increasing shortfall of up to 77,000 RBC units by 2035. DISCUSSION: Our study highlights the need for continuous monitoring of trends of blood donations and blood transfusions in order to take proactive measures aimed at preventing blood shortages in Switzerland. Measures should be taken to improve donor retention in order to prevent a further erosion of the blood donor base.

Too Many Blood Donors - Response Bias in the Swiss Health Survey 2012.

BACKGROUND: Data on blood donor status obtained from general surveys and health interview surveys have been widely used. However, the integrity of data on self-reported blood donor status from surveys may be threatened by sampling and non-sampling error. Our study aimed to compare self-reported blood donors (including one-time as well as regular donors) from the Swiss Health Survey 2012 (SHS) with register-based blood donors recorded by blood establishments and evaluate the direction and magnitude of bias in the SHS. METHODS: We compared population-weighted SHS point estimates of the number of blood donors with their corresponding 95% confidence intervals to the respective figures from blood donor registries (birth cohorts 1978-1993) and estimates of donors based on period donor tables derived from blood donor registries (birth cohorts 1920-1993). RESULTS: In the birth cohorts 1978-1993, the SHS-predicted number of donors was 1.8 times higher than the respective number of donors based on registry data. Adjusting for foreign and naturalized Swiss nationals that immigrated after their 18th birthday, the SHS overall predicted number of donors was 1.6 times higher. Similarly, SHS estimates for the 1920-1993 birth cohorts were 2.4 and 2.1 times higher as compared to register-based estimates. Generally, the differences between SHS and register-based donors were more pronounced in men than in women. CONCLUSION: Self-reported blood donor status in the SHS is biased. Estimates of blood donors are substantially higher than respective estimates based on blood donor registries.

MNSs genotyping by MALDI-TOF MS shows high concordance with serology, allows gene copy number testing and reveals new St(a) alleles.

Results of genotyping with true high-throughput capability for MNSs antigens are underrepresented, probably because of technical issues, due to the high level of nucleotide sequence homology of the paralogous genes GYPA, GYPB and GYPE. Eight MNSs-specific single nucleotide polymorphisms (SNP) were detected using matrix-assisted laser desorption/ionization, time-of-flight mass spectrometry (MALDI-TOF MS) in 5800 serologically M/N and S/s pre-typed Swiss blood donors and 50 individuals of known or presumptive black African ethnicity. Comparison of serotype with genotype delivered concordance rates of 99·70% and 99·90% and accuracy of genotyping alone of 99·88% and 99·95%, for M/N and S/s, respectively. The area under the curve of peak signals was measured in intron 1 of the two highly homologous genes GYPB and GYPE and allowed for gene copy number variation estimates in all individuals investigated. Elevated GYPB:GYPE ratios accumulated in several carriers of two newly observed GYP*401 variants, termed type G and H, both encoding for the low incidence antigen St(a). In black Africans, reduced GYPB gene contents were proven in pre-typed S-s-U- phenotypes and could be reproduced in unknown specimens. Quantitative gene copy number estimates represented a highly attractive supplement to conventional genotyping, solely based on MNSs SNPs.

Initial cord blood unit volume affects mononuclear cell and CD34+ cell-processing efficiency in a non-linear fashion.

BACKGROUND AIMS: Umbilical cord blood (UCB) is a source of hematopoietic stem cells that initially was used exclusively for the hematopoietic reconstitution of pediatric patients. It is now suggested for use for adults as well, a fact that increases the pressure to obtain units with high cellularity. Therefore, the optimization of UCB processing is a priority. METHODS: The present study focused on parameters influencing total nucleated cell (TNC), mononucleated cell (MNC) and CD34+ cell (CD34C) recovery after routine volume reduction of 1553 UCB units using hydroxyethyl starch-induced sedimentation with an automated device, under routine laboratory conditions. RESULTS: We show that the unit volume rather than the TNC count significantly affects TNC, MNC and CD34C processing efficiency (PEf), and this in a non-linear fashion: when units were sampled according to the collection volume, including pre-loaded anticoagulant (gross volume), PEf increased up to a unit volume of 110-150 mL and decreased thereafter. Thus units with initial gross volumes < 90 mL and > 170 mL similarly exhibited a poor PEf. CONCLUSIONS: These data identify unit gross volume as a major parameter influencing PEf and suggest that fractionation of large units should be contemplated only when the resulting volume of split units is > 90 mL.

Hyperimmune anti-HBs plasma as alternative to commercial immunoglobulins for prevention of HBV recurrence after liver transplantation.

BACKGROUND: Hepatitis B immune globulins (HBIG) in combination with nucleos(t)ide analogues (NA) are effectively used for the prevention of hepatitis B virus (HBV) recurrence after liver transplantation (LT). However, associated treatment costs for HBIG are exceedingly high. METHODS: Fresh frozen plasma obtained from blood donors with high anti-HBs levels (hyperimmune plasma, HIP) containing at least 4,500 IU anti-HBs was used as alternative treatment for HBV recurrence prophylaxis post-LT. RESULTS: Twenty-one HBV-related LT recipients received HIP starting at transplantation, followed by long-term combination treatment with NA. Mean follow-up time was 4.5 years (range 0.5-12.6) and each patient received on average 8.2 HIP per year (range 5.8-11.4). Anti-HBs terminal elimination kinetic after HIP administration was 20.6 days (range 13.8-30.9), which is comparable to values reported for commercial HBIG products. All 21 patients remained free of HBV recurrence during follow-up and no transfusion-transmitted infection or other serious complication was observed. Seven patients developed reversible mild transfusion reactions. The cost for one HIP unit was US$140; average yearly HBIG treatment cost was US$1,148 per patient, as compared to US$25,000-100,000 for treatment with commercial HBIG. CONCLUSION: The results of this study suggest that the use of HIP may be a useful and economical approach for the prevention of HBV recurrence post-LT if used in combination with NA. Additional prospective controlled studies in larger populations are needed to confirm these results.

"In vitro" and multicolor phenotypic characterization of cell subpopulations identified in fresh human adipose tissue stromal vascular fraction and in the derived mesenchymal stem cells.

BACKGROUND: The stromal vascular fraction (SVF) is a heterogeneous cell population derived from the adipose tissue. There is still a lack of information concerning the characterization of the cell subpopulations constituting the SVF as well as its mesenchymal and haematopoietic potential. Furthermore there are great variations in its phenotypical characterization. METHODS: Composition of SVF was investigated by FACS analysis, cytological and "in vitro" assays. We studied CD34+ population by combining FACS with human CFC (colony-forming-cell haematopoietic assay). The endothelial fraction was investigated by quantifying the co-expression of specific markers (CD146, CD105, CD31 and UEA-1). Mesenchymal potential was assessed by CFU-F assay and cultured AT-MSC were characterized by a 5-color FACS analysis. The multipotent differentiation potential (osteogenic, adipogenic and chondrogenic) was investigated both at cellular and molecular level. RESULTS: We identified in the SVF two CD34+ populations with a marked difference in the intensity of antigen expression, the majority of the cells expressing CD34 at low intensity. Moreover, two CD146+ cell populations were clearly distinguishable in the SVF:a CD146 dim accounting for 9.9% of the total SVF cells and a CD146+ bright cell population accounting for about 39.3%. The frequency of CFC clones was comparable with the one reported for peripheral blood. Endothelial cells account for about 7.7% of the SVF cells. AT-MSC differenced in the osteogenic adipogenic and chondrogenic lineage. CONCLUSION: The SVF is not a homogeneous cell population, and its final composition could be influenced both by the flow cytometric technique analysis and the SVF extraction steps. The CFU-F frequency in the SVF was 1/4880, a value about seven times greater than the data reported for bone marrow. The antigenic profile of AT-MSC was comparable with bone-marrow derived MSC. AT-MSC were able to differentiate along the osteogenic adipogenic and chondrogenic lineages. The data here reported, further contribute to the characterization of SVF, a tissue providing an alternative as a source of MSC for clinical applications.

Transfusion-transmitted infections.

Although the risk of transfusion-transmitted infections today is lower than ever, the supply of safe blood products remains subject to contamination with known and yet to be identified human pathogens. Only continuous improvement and implementation of donor selection, sensitive screening tests and effective inactivation procedures can ensure the elimination, or at least reduction, of the risk of acquiring transfusion transmitted infections. In addition, ongoing education and up-to-date information regarding infectious agents that are potentially transmitted via blood components is necessary to promote the reporting of adverse events, an important component of transfusion transmitted disease surveillance. Thus, the collaboration of all parties involved in transfusion medicine, including national haemovigilance systems, is crucial for protecting a secure blood product supply from known and emerging blood-borne pathogens.