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Introduction: Immunoadsorption (IA) of isohemagglutinins is an often-crucial procedure in preparation of major ABO blood group-incompatible living donor kidney transplantation (ABOi LDKT). Standard citrate-based anticoagulation during the procedure has potential disadvantages for distinct patient groups. In this study, we report our experience with an alternative anticoagulation scheme using heparin during IA for selected patients. Methods: We conducted a retrospective analysis of all patients who underwent IA with heparin anticoagulation between February 2013 and December 2019 at our institution with focus on the safety and efficacy of the adapted procedure. For further validation, we compared graft function, graft survival, and overall survival with those of all recipients of living donor kidney transplants with or without pretransplant desensitizing apheresis for ABO antibodies at our institution during the same period. Results: In thirteen consecutive patients prepared for ABOi LDKT with IA with heparin anticoagulation, no major bleeding or other significant complications were observed. All patients achieved sufficient isohemagglutinin titer reduction to proceed to transplant surgery. Graft function, graft survival, and overall survival did not significantly differ from patients treated with standard anticoagulation for IA or ABO compatible recipients of living donor kidneys. Conclusion: IA with heparin in preparation of ABOi LDKT is safe and feasible for selected patients after internal validation.

BACKGROUND: A triple storage (TS) set allows for pathogen inactivation (PI) treatment of triple-dose apheresis platelet products with amotosalen + UVA. We evaluated the quality and metabolic parameters of platelet concentrates (PCs) pathogen inactivated and stored for 7 days. MATERIALS AND METHODS: Twelve triple-dose products collected with two different apheresis platforms were treated with amotosalen+UVA. Products were split into three single-dose units. Testing was made pretreatment, after splitting, at days 5 and 7 of storage. RESULTS: Single-dose PI PCs had a mean platelet content of 2.89 ± 0.35 x 1011 . From baseline to day 7, pH remained stable (7.1 ± 0.1 vs. 7.0 ± 0.1), pO2 increased (11.3 ± 2.4 vs. 18.3 ± 3.5 kPa) as did LDH (201 ± 119 vs. 324 ± 203 U/L) and lactate (3.6 ± 1.7 vs. 12.1 ± 1.5 mmol/L) (all p

Efficacy of donated COVID-19 convalescent plasma (dCCP) is uncertain and may depend on antibody titers, neutralizing capacity, timing of administration, and patient characteristics.In a single-center hypothesis-generating prospective case-control study with 1:2 matched dCCP recipients to controls according to disease severity at day 1, hospitalized adults with COVID-19 pneumonia received 2 × 200 ml pathogen-reduced treated dCCP from 2 different donors. We evaluated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in COVID-19 convalescent plasma donors and recipients using multiple antibody assays including a Coronavirus antigen microarray (COVAM), and binding and neutralizing antibody assays. Outcomes were dCCP characteristics, antibody responses, 28-day mortality, and dCCP -related adverse events in recipients.Eleven of 13 dCCPs (85%) contained neutralizing antibodies (nAb). PRT did not affect dCCP antibody activity. Fifteen CCP recipients and 30 controls (median age 64 and 65 years, respectively) were enrolled. dCCP recipients received 2 dCCPs from 2 different donors after a median of one hospital day and 11 days after symptom onset. One dCCP recipient (6.7%) and 6 controls (20%) died (p = 0.233). We observed no dCCP-related adverse events. Transfusion of unselected dCCP led to heterogeneous SARS CoV-2 antibody responses. COVAM clustered dCCPs in 4 distinct groups and showed endogenous immune responses to SARS-CoV-2 antigens over 14-21 days post dCCP in all except 4 immunosuppressed recipients.PRT did not impact dCCP anti-virus neutralizing activity. Transfusion of unselected dCCP did not impact survival and had no adverse effects. Variable dCCP antibodies and post-transfusion antibody responses indicate the need for controlled trials using well-characterized dCCP with informative assays.

Immune-mediated cytopenia after allogeneic haematopoietic stem-cell transplantation is rare. The pathophysiology of immune-mediated anaemia, thrombocytopenia, and neutropenia, which occur alone or in combination with other cytopenias, is unclear and most probably a consequence of immune dysregulation. Risk factors for this complication have been identified in retrospective studies but these should be interpreted with caution and should not be generalised to this heterogeneous patient population. Diagnosis is challenging, requires awareness of such complications, and has to be differentiated from a multitude of other, and sometimes overlapping, possible complications. The clinical course of immune-mediated cytopenia is highly variable. Treatment requires an interdisciplinary approach and ranges from observation to symptomatic measures and directed therapies. Intensive immunosuppression is associated with an increased risk of infections and relapse, and current treatments are based on approaches in patients who have not undergone transplantation. Plasma cell-directed therapies, immunomodulation, and receptor-stimulating agents can be used to treat immune-mediated cytopenia.

To investigate the class-dependent properties of anti-viral IgM antibodies, we use membrane antigen capture activated cell sorting to isolate spike-protein-specific B cells from donors recently infected with SARS-CoV-2, allowing production of recombinant antibodies. We isolate 20, spike-protein-specific antibodies of classes IgM, IgG, and IgA, none of which shows any antigen-independent binding to human cells. Two antibodies of class IgM mediate virus neutralization at picomolar concentrations, but this potency is lost following artificial switch to IgG. Although, as expected, the IgG versions of the antibodies appear to have lower avidity than their IgM parents, this is not sufficient to explain the loss of potency.

We analysed iron biomarkers and their relationships in 30 subjects with HFE mutations and moderate hyperferritinaemia undergoing iron removal at our blood donation centre. Body mass index (BMI) and liver enzymes were assessed. Serum iron (SI), ferritin, transferrin saturation (TSAT), hepcidin and non-transferrin bound iron (NTBI) were measured serially. Seventeen subjects had p.C282Y/p.C282Y, nine p.C282Y/p.H63D, four p.H63D/p.H63D. Median age (p = 0.582), BMI (p = 0.500) and ferritin (p = 0.089) were comparable. At baseline, 12/17 p.C282Y/p.C282Y and 2/9 p.C282Y/p.H63D had measurable NTBI (p = 0.003). The p.C282Y/p.C282Y had higher TSAT (p 0.001), lower hepcidin (p = 0.031) and hepcidin/ferritin ratio (p = 0.073). After treatment, iron indices were similar among groups, except TSAT (higher in p.C282Y/p.C282Y; p = 0.06). Strong relationships were observed between ferritin and TSAT (R = 0.71), NTBI and TSAT (R = 0.61), NTBI and SI (R = 0.54) in p.C282Y/p.C282Y. Hepcidin correlated weakly with ferritin in p.C282Y/p.C282Y (R = 0.37) but strongly in p.C282Y/p.H63D (R = 0.66) and p.H63D/p.H63D (R = 0.72), while relationships with TSAT were weak (R = 0.27), moderate (R = 0.55) and strong (R = 0.61), respectively. Low penetrance p.C282Y/p.C282Y phenotype displays hepcidin dysregulation and biochemical risk for iron toxicity.

BACKGROUND Universal pathogen inactivation of platelet concentrates (PCs) using amotosalen/ultraviolet A with 7-day storage was implemented in Switzerland in 2011. Routine-use data were analyzed at the University Hospital Basel, Switzerland. STUDY DESIGN A retrospective two-cohort study of patient and PC characteristics, component usage, patient outcomes, count increments (CIs), and adverse events were analyzed for two consecutive 5-year periods with either 0- to 5-day-old conventional PC (C-PC) (n = 14,181) or 0- to 7-day-old pathogen-inactivated PC (PI-PC) (n = 22,579). RESULTS In both periods, PCs were issued for transfusion on a "first in, first out" basis. With 7-day PI-PC, wastage was reduced from 8.7% to 1.5%; 16.6% of transfused PI-PCs were more than 5 days old. Transfusion of PI-PC more than 5 days old compared with 5 days old or less did not increase platelet and RBC use on the same or next day as an indirect measure of hemostasis and did not increase transfusion reactions. Mean corrected count increments (CCIs) for PI-PC stored for 5 days or less were 22.6% lower than for C-PC (p

Background CD34+ cell count correlates with engraftment potency after autologous stem cell transplantation. Assessment of CD34+ mainly occurs after apheresis and before cryopreservation with dimethyl sulfoxide (DMSO). The influence of postthaw CD34+ cell numbers over time to engraftment is not well studied, and determination of postthaw CD34+ cell counts is challenging for a variety of reasons. The aim of this retrospective study was to systematically assess the value of postthaw CD34+ cell counts in autologous grafts with and without DMSO removal. Study design and methods Between January 2008 and December 2015, 236 adult patients underwent a total of 292 autologous stem cell transplantations. Median age at transplantation was 56 years, and the main indication was multiple myeloma (60%). DMSO removal was done in 96 grafts (33%), either by centrifugation or by Sepax method. Results Patients receiving grafts containing DMSO showed a significantly faster platelet (p = 0.02) and RBC (p = 0.001) engraftment. DMSO removal was not associated with fewer infusion-related adverse events. We observed a good correlation between CD34+ cell count after apheresis and CD34+ cell count after thawing/washing (r = 0.931). Ninety grafts (31%) showed a significant loss of viable CD34+ cells, which translated into a delayed engraftment. Conclusion DMSO removal was associated with delayed platelet and RBC engraftment without preventing adverse events. CD34+ cell enumeration after thawing remains difficult to perform, but grafts showing higher cell loss during cryopreservation and thawing are associated with slower engraftment. Prospective studies on the role of DMSO removal and postthaw CD34+ enumeration using defined protocols are needed.

BACKGROUND Our goal was to determine vitamin B12 (cobalamin) deficiency with different diagnostic strategies, to propose the best possible laboratory strategy, and to synthesize the relevance of biomarkers in the diagnosis of a cobalamin deficiency. METHODS We performed a secondary data analysis. The testing strategies were (i) vitamin B12 solely, (ii) holotranscobolamin solely, (iii) vitamin B12 and holotranscobolamin, and (iv) reflex testing of holotranscobalamin in samples with vitamin B12 < 300 pmol. A set of 3,044 laboratory samples with vitamin B12 and holotranscobalamin serum values from unselected in- and outpatients from a secondary care hospital. A sample was classified as cobalamin deficient when low values of vitamin B12 < 137 pmol/L or holotranscobalamin ≤ 37 pmol/L were measured. RESULTS Low cobalamin values were identified in 591 (19.4%) samples either according to low vitamin B12 values (305; 10.0%) or low holotranscobalamin values (436; 14.3%). For 2,404 values with vitamin B12 < 300 pmol/L, the additional measurement of holotranscobalamin (reflex-testing) enabled the detection of an additional 278 (9.1%) deficiencies. When the grey zone was decreased to 138 - 219 pmol/L, the reflex testing of an additional 1,240 samples identified a total of 511 (16.8%) samples as cobalamin deficient. CONCLUSIONS The identification of cobalamin deficiency or sufficiency highly depends on the diagnostic strategy. A reflex testing with a grey zone for vitamin B12 < 220 pmol/L identifies cobalamin deficiency cost efficiently in 86.5% cases (511 out of 591). Physicians should apply a uniform strategy on how to address the diagnosis of cobalamin deficiency and indication for treatment. In-hospital guidelines, which describe methodology and sensitivity of the locally used assays for vitamin B12 and holotranscobalamin could guide them.

Background and objectives Antibodies (Ab) against HLA and HPA antigens play an important role in HCT. In this prospective study we evaluated prevalence and kinetics of HLA- and HPA-Ab after HCT, including a possible donor-recipient transfer and their clinical relevance in respect to platelet transfusion refractoriness (PTR). Materials and methods Patients were consecutively recruited. Ab were determined by microbead assay technique and a mean fluorescence intensity cut-off of 1,000. Results At baseline, 21 donors (42 %) and 27 patients (54 %) had HLA-Ab with a mean panel reactivity (cPRA) of 34.9 ± 29.4 % and 46.1 ± 36.5 %, respectively. We observed a significant higher number of HLA-Ab specificities in female donors and patients and a predominance of HLA-class I Ab. At day 0 we detected an increase of HLA-Ab (from 526 to 673) and cPRA (55.2 ± 31.9 %). Thirty-six patients (72 %) developed new HLA-Ab, mainly 3 weeks after HCT. In 7 patients an HLA-Ab with the same specificity as detected in the corresponding donor emerged, suggesting a possible transfer from the donor to the recipient. Overall, MFI showed a high variation. Type and number of transfusions were not associated with number and intensity of HLA-Ab (ρ: -0.05 – 0.02). Number of HLA-Ab, cPRA and intensity were not associated with PTR, which occurred in 9 patients (18 %) and none had bleeding WHO > 2. Conclusions Although a considerable number of patients have and develop HLA-Ab before and early after HCT, we found no association with PTR and bleeding and management should be individualized.

Convalescent plasma to treat coronavirus disease 2019 (COVID-19) is currently the focus of numerous clinical trials worldwide, but the criteria of treatment efficacy remain largely unknown. Here, we describe a severely immunosuppressed patient following rituximab and chemotherapy for chronic lymphoid leukemia, who became infected by SARS-CoV-2. His prolonged viral disease was successfully cured after four cycles of convalescent plasma. Its immunomodulatory properties led to the rapid improvement of inflammation, pneumonia and blood cell counts, already after the first cycle. Importantly, the cumulative increase in anti-SARS-CoV-2 neutralizing antibodies following each plasma transfusion was associated to progressive viral clearance, resulting in clinical recovery from infection. Our data provide insight into the different modes of action of plasma components. Understanding the underlying mechanisms will help to optimize the treatment of COVID-19 patients.

Introduction Since the 1970s outcome of aplastic anemia (AA) patients has improved significantly due to the introduction of immunosuppressive therapy (IST) and allogeneic hematopoietic transplantation (HCT). However, patients may suffer from persistent disease, relapse, clonal evolution, graft-versus-host disease and other late effects. Here, we analyse very long-term outcome of all AA patients at our institution comparing not only survival, but also response status and complications. Methods Patient charts of all 302 AA patients treated between 1973 and 2017 at the University Hospital Basel, Switzerland, were retrospectively analysed. Results First line treatment was IST in 226 (75%) and HCT in 76 (25%) patients. Overall survival at 30 years was similar in patients treated initially by HCT and IST (44% (±14%), and 40% (± 9%) respectively, with better results in more recent years. Partial and no response occurred more frequently after IST, relapse incidence after IST was 24 %, whereas non-engraftment and graft failure was documented in 15 patients (19 %) after HCT. Clonal evolution to myelodysplastic syndrome / acute myeloid leukemia was 16 % at 25 years in IST patients, 1.3 % in HCT patients, iron overload (18 versus 4 %, p = 0.002) and cardiovascular events (11 versus 1 %, p=0.011) occured significantly more often in IST than HCT treated patients. The majority of long-term survivors, 96% of those alive at 25 years, were in complete remission at last follow up, irrespective of the initial treatment modality. Conclusion Very long term survivors after AA are those with stable hematopoietic recovery.

Background and Summary: Extracorporeal photopheresis (ECP) is a leukapheresis-based procedure used in the therapy of acute and chronic graft-versus-host disease (aGvHD, cGvHD) and other diseases. Based on the substantial efficacy and the excellent safety profile in the absence of immunosuppression ECP has established itself as a major treatment form for steroid-refractory GvHD. Here we review the current literature on ECP as a treatment option for patients with aGvHD as well as cGvHD. Key Messages: ECP is a well-established second-line therapy for cGvHD. Its role in the treatment of aGvHD is less clear but also points towards an effective second-line therapy option. In the future ECP could play a role in the prevention of GvHD. More experimental and randomized controlled trials are needed to define the best patient selection criteria, settings, and therapy regimens for GvHD.

Transfusions are the mainstay of supportive therapy in patients with aplastic anemia (AA) and may lead to anti- HLA alloimmunization, thereby also increasing the risk for donor-specific antibodies in the setting of HLA-mismatched transplantation. Historically, AA patients were thought to be at particularly high risk for HLA alloimmunization. In past decades, blood product manufacturing (leukoreduction) and HLA antibody testing have improved significantly by single antigen bead (SAB) technology. It is currently unknown how those developments have impacted HLA alloimmunization and treatment outcome in patients with AA. We retrospectively investigated 54 AA patients treated by immunosuppressive therapy or allogeneic hematopoietic cell transplantation after the introduction of the SAB assay at our center. We compared the HLA antibody results to a historical AA cohort (n = 26), treated before introduction of leukoreduced blood products from 1975 to 1995. HLA alloimmunization was detected in 43 of 54 (80%) recently treated patients. Past pregnancy, female gender, disease severity, age, and a history of other transfusions were significantly associated with a larger number or higher intensity (mean fluorescence intensity) of HLA antibodies. Treatment outcome including bleeding episodes, response to treatment, engraftment, graft-versus-host disease, and overall survival was not associated with HLA alloimmunization. In the historical cohort a significantly higher number of HLA antibodies (P < .01) with a higher mean fluorescent intensity (P < .01) was observed. HLA alloimmunization remains frequent in AA tested by current techniques, but it has significantly decreased since prior decades and does not affect treatment outcome. © 2021 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Amotosalen and ultraviolet A (UVA) photochemical-based pathogen reduction using the Intercept™ Blood System (IBS) is an effective and established technology for platelet and plasma components, which is adopted in more than 40 countries worldwide. Several reports point towards a reduced platelet function after Amotosalen/UVA exposure. The study herein was undertaken to identify the mechanisms responsible for the early impairment of platelet function by the IBS. Twenty-five platelet apheresis units were collected from healthy volunteers following standard procedures and split into 2 components, 1 untreated and the other treated with Amotosalen/UVA. Platelet impedance aggregation in response to collagen and thrombin was reduced by 80% and 60%, respectively, in IBS-treated units at day 1 of storage. Glycoprotein Ib (GpIb) levels were significantly lower in IBS samples and soluble glycocalicin correspondingly augmented; furthermore, GpIbα was significantly more desialylated as shown by Erythrina Cristagalli Lectin (ECL) binding. The pro-apoptotic Bak protein was significantly increased, as well as the MAPK p38 phosphorylation and caspase-3 cleavage. Stored IBS-treated platelets injected into immune-deficient nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice showed a faster clearance. We conclude that the IBS induces platelet p38 activation, GpIb shedding and platelet apoptosis through a caspase-dependent mechanism, thus reducing platelet function and survival. These mechanisms are of relevance in transfusion medicine, where the IBS increases patient safety at the expense of platelet function and survival.

BACKGROUND Alloimmunization against human platelet antigens (HPAs) during pregnancy is rare but can lead to severe bleeding disorders, such as fetal and neonatal alloimmune thrombocytopenia. STUDY DESIGN AND METHODS In a cohort of 241 uncomplicated pregnancies, we investigated the immunogenicity of HPA mismatches and correlated HLA sensitization with HPA antibody formation. HPA antibodies were measured with a Luminex-based multiplex assay. RESULTS HPA mismatches were observed in 109 of 241 pregnancies (45%), but child-specific HPA antibodies were only found in two of 109 cases (2%), indicating a low immunogenicity. Only nine of 241 women (4%) had detectable HPA antibodies. HLA sensitization was identified as a strong and independent predictor for HPA antibody formation (hazard ratio, 10.2; 95% confidence interval, 1.8-193; p = 0.006), whereas the number of pregnancies was not. CONCLUSION Our observational data indicated a low immunogenicity of HPA and suggest that a broader immune response—inferred by HLA sensitization—is probably associated with HPA antibody induction.

Background. COVID-19, caused by the SARS-CoV-2 virus, is a pandemic disease with high morbidity and mortality. Currently, available therapeutic options for COVID-19 are limited. Prior experience in epidemics with convalescent plasma (CP) containing antibodies to viruses has demonstrated variable indications of therapeutic efficacy for: Influenza, Argentine Hemorrhagic Fever, and SARS. Characterizing antibody titers to viruses has indicated correlation with therapeutic efficacy. Convalescent COVID-19 patients with potent SARS-CoV-2 antibody responses can serve as plasma donors for immune therapy. However, antibody responses are variable, many donors are first-time higher risk blood donors, and rapid assays to select optimal CP immune efficacy are limited. Pathogen inactivation (PI) of CP can reduce the risk of transfusion-transmitted infection by unrecognized pathogens. Objectives. This study characterized COVID-19 PI-CP activity; and evaluated efficacy and safety of PI CP transfusion in a case matched controlled cohort of acute COVID-19 patients. Methods. COVID-19 apheresis CP (650 - 1300 mL) was collected from nasopharyngeal PCR + outpatients following 2 PCR negative tests or 28 days after symptom resolution. Amotosalen-UVA PI of CP (INTERCEPT Blood System for Plasma) was performed, and antibody efficacy before and after PI was characterized by: VSV reporter pseudo-virus plaque neutralization (RVPN) NT-50 titer (Vitalant Research Institute, San Francisco), antibody to S and N virus proteins by agglutination-dependent antibody PCR (ADAP, Enable Biosciences, San Francisco), virus ACE-2 soluble receptor neutralization assay (Enable Biosciences), and SARS-CoV-2 antibody profile by coronavirus microarray (University of California, Irvine). Patient inclusion criteria were: confirmed SARS-CoV-2 infection, hospitalization, pulmonary infiltrates, availability of ABO compatible CP, and informed consent. CP patients were matched with control patients (CTRL) for disease severity at diagnosis by standardized clinical risk score (W. Liang et al JAMA Intern Med 2020) and concomitant Tocilizumab use. CP Patients received a total of 400 mL of PI CP from 2 donors over 48 hours and standard therapy. CTRL patients received standard COVID-19 therapy without CP. The primary outcome was in-hospital death to day 28. Secondary outcomes included: progression to intubation, admission to ICU, time to discharge, serious adverse events, NP viral clearance, plasma viral clearance, and humoral immune responses. Differences between CP and CTRL patients were assessed by the Mann-Whitney test for continuous variables, and by Fisher's exact test for categorical variables. Progression to ICU and intubation were analyzed as odds ratios calculated by conditional logistic regression. Results. 15 CP and 30 CTRL patients were enrolled. One CP patient was admitted in cardiogenic shock. Only 2 of 15 CP cohort patients had detectable IgG antibody to SARS CoV-2 S1 antigen at study entry. 3 of 15 PI CP donors had negligible SARS CoV-2 IgG antibodies to all antigens, and demonstrated poor neutralization efficacy. 12/15 CP had effective RVPN titers (> 1:80), RVPN titers were correlated with ACE-2 neutralization antibody titers (r2 = 0.83), and had significant activity specific for S and RBD antigens by microarray profiling (Figure 1). SARS CoV-2 antibody levels were variable between CP donors, but not impacted by PI (Figure 1). Baseline characteristics of CP and matched CTRL patients were similar (Table 1). Sensitivity analysis was performed assessing mortality after exclusion of one CTRL patient admitted in cardiogenic shock and the 2 respective controls. In-hospital 28-day mortality was lower in the CP cohort (0/14) compared to 5/28 CTRL, p = 0.151, 2-sided Fisher's exact test. Progression to intubation, ICU admission, and days in hospital were not significantly different (Table 1). There was a trend toward decreased inflammatory response (CRP normalization) in CP patients. Conclusions. In hospital mortality of COVID-19 patients was lower in the PI-CP cohort, but not statistically significant. 15% of CP had ineffective antibody by multiple assays. However, PI did not impact CP anti-SARS-CoV-2 activity. PI of plasma provides reduced risk of transfusion transmitted infection from COVID-19 CP donors. In this study, PI CP was safe, and may be effective for early treatment of hospitalized COVID-19 patients. Disclosures von Goetz: Cerus Corporation: Current Employment, Current equity holder in publicly-traded company. Khan:Nanommune Inc.: Current equity holder in private company. Tsai:Enable Biosciences: Current Employment. Robinson:Enable Biosciences: Current Employment. Seftel:Enable Biosciences: Current Employment, Current equity holder in private company. Bagri:Cerus Corporation: Current Employment, Current equity holder in publicly-traded company. Corash:Cerus Corporation: Current Employment, Current equity holder in publicly-traded company.

Herein we describe a case of febrile non-hemolytic reaction (FNHTR) in a 64-year-old male 20 min after the transfusion of one red blood cell unit. 20 days prior the patient had undergone an allogeneic hematopoietic stem cell transplantation (HCT) from an unrelated donor with minor ABO disparity. The patient had been treated for plasma cell myeloma with multiple transfusions in the past, but no transfusion reactions or alloimmunization had been reported.

According to many textbooks, iron deficiency (ID) is associated with reactive thrombocytosis. In this study, we aimed to investigate the correlation between serum ferritin levels and platelet counts in a large cohort of healthy blood donors. We included all whole blood and apheresis donors aged 18 years or older with at least one ferritin measurement and one platelet count performed at the same visit between 1996 and 2014. A total of 130 345 blood counts and ferritin measurements obtained from 22 046 healthy donors were analysed. Overall, no correlation between serum ferritin and platelet count was observed (r = -0.03, ρ = 0.04 for males, and r = 0.01, ρ = -0.02 for females, respectively). Associations remained clinically negligible after adjusting for age, time since previous blood donation, number of donations and restricting the analysis to ferritin deciles. In this large, retrospective single-centre study, correlations between low ferritin and platelet count in a large and homogeneous cohort of healthy donors were negligible. Further studies in patients with more severe anaemia and patients with inflammation are warranted.

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.

Background and aim Hepatitis E virus (HEV) is a virus of emerging importance to transfusion medicine. Studies from several European countries, including Switzerland, have reported high seroprevalence of hepatitis E as a consequence of endemic infections. Published HEV seroprevalence estimates within developed countries vary considerably; primarily due to improved diagnostic assays. The purpose of this study was to investigate the seroprevalence of anti-HEV IgG in Swiss blood donations. Methods: We used the highly sensitive Wantai HEV IgG EIA and assessed regional distribution patterns. We analysed age- and sex-matched archive plasma dating back 20 years from canton Bern to investigate recent changes in HEV seroprevalence levels. Results: On average, 20.4% (95% confidence intervals: 19.1–21.8) of the 3,609 blood samples collected in 2014–16 were anti-HEV IgG positive; however, distinct differences between geographical regions were observed (range: 12.8–33.6%). Seroprevalence increased with age with 30.7% of males and 34.3% of women being positive donors over > 60 years old. Differences between sexes may be attributed to dissimilarities in the average age of this group. Within the specified region of the Bern canton, overall prevalence has declined over two decades from 30.3% in 1997/98 to 27.0% in 2006 and 22.3% in 2015/6. Conclusions: HEV seroprevalence in Switzerland is high, but has declined over the last decades. The result shows that primarily endemic HEV infections occur and that current blood products may pose a risk to vulnerable transfusion recipients. Nucleic acid screening of all blood products for HEV will begin in November 2018.

CD34+ cell count correlates with engraftment potency after autologous stem cell transplantation. Assessment of CD34+ mainly occurs after apheresis and before cryopreservation with dimethyl sulfoxide (DMSO). The influence of postthaw CD34+ cell numbers over time to engraftment is not well studied, and determination of postthaw CD34+ cell counts is challenging for a variety of reasons. The aim of this retrospective study was to systematically assess the value of postthaw CD34+ cell counts in autologous grafts with and without DMSO removal.Between January 2008 and December 2015, 236 adult patients underwent a total of 292 autologous stem cell transplantations. Median age at transplantation was 56 years, and the main indication was multiple myeloma (60%). DMSO removal was done in 96 grafts (33%), either by centrifugation or by Sepax method.Patients receiving grafts containing DMSO showed a significantly faster platelet (p = 0.02) and RBC (p = 0.001) engraftment. DMSO removal was not associated with fewer infusion-related adverse events. We observed a good correlation between CD34+ cell count after apheresis and CD34+ cell count after thawing/washing (r = 0.931). Ninety grafts (31%) showed a significant loss of viable CD34+ cells, which translated into a delayed engraftment.DMSO removal was associated with delayed platelet and RBC engraftment without preventing adverse events. CD34+ cell enumeration after thawing remains difficult to perform, but grafts showing higher cell loss during cryopreservation and thawing are associated with slower engraftment. Prospective studies on the role of DMSO removal and postthaw CD34+ enumeration using defined protocols are needed.

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.

Natural killer (NK) cells require interaction of inhibitory surface receptors with human leukocyte antigen (HLA) ligands during development to acquire functional competence in a process termed “licensing.” The quantity of HLA required for this process is unknown. Two polymorphisms affecting HLA-C surface expression (rs9264942 and rs67384697) have recently been identified, and shown to influence progression of HIV infection. We typed a cohort of healthy donors for the two HLA-C-related polymorphisms, KIR2DL1 and KIR2DL3, and their respective HLA-C ligands and analyzed how HLA ligands influenced licensing status of killer cell immunoglobulin-like receptor (KIR)+ NK cells in terms of degranulation and cytokine production in response to HLA-deficient target cells. The presence of respective HLA class I ligands increased the function of KIR2DL1+ and KIR2DL3+ NK cells in a dose-dependent manner. In contrast, neither of the HLA-C-related polymorphisms nor the quantity of cell surface HLA-C had any significant effect on NK cell function. Interestingly, HLA-Cw7—an HLA-C allele with low surface expression—licensed KIR2DL3+ NK cells more strongly than any other KIR2DL3 ligand. The quantity of cell surface HLA-C does not appear to influence licensing of NK cells, and the HLA-C-related polymorphisms presumably influence HIV progression through factors unrelated to NK cell education.

Background There is considerable heterogeneity in processing of stem cells for hematopoietic stem cell transplantation across Europe. The Foundation for the Accreditation of Cellular Therapy (FACT)–Joint Accreditation Committee International Society for Cellular Therapy and European Society for Blood and Marrow Transplantation (EBMT) (JACIE) standards provide minimum guidelines that, however, leave room for significant variations in practices at the individual transplantation center (TC). Methods To better understand the extent of heterogeneity in storage conditions, quality controls (QCs), graft processing and disposal, a questionnaire was developed, reviewed by the Cellular Therapy and Immunobiology Working Party (CTIWP) and sent to all EBMT TCs. Results In this study, 288 TCs from 46 countries (32 European, 14 associated) responded to the survey. Long-term storage is performed mainly either in liquid nitrogen or in the vapor phase of liquid nitrogen with 10% dimethyl sulfoxide (DMSO; 58% of centers). In case of microbiological contamination, most TCs make a case-by-case decision in collaboration with the clinicians. CD34+ counts are performed routinely either before and/or after thawing. Some centers perform additional QCs. DMSO is generally not removed (83%) and the graft is thawed at the bedside (68%) in a water bath (78%). There is heterogeneity between the centers regarding duration of storage and graft disposal. Discussion Overall, this survey demonstrates that the majority of responding TCs uses standardized procedures (intracenter standardization). However, significant intercenter variations persist, which warrant further standardization and investigations on clinical and financial consequences. Additionally, efforts should be undertaken to provide more specific international guidelines on storage duration and graft disposal, which may also have an important impact on health care services worldwide.

Background and Objectives For the prevention of blood shortages, it is essential for blood banks to design and implement donor recruitment and donor retention strategies that take into account the determinants of donor return. Material and Methods We studied the behaviour of first-time blood donors in the region of Basel, Switzerland, between 1996 and 2011 and described factors associated with transition from active to inactive donor in two successive first-time donor cohorts (1996–2002, 2003–2008). Results The risk of becoming an inactive donor was associated with being younger and female, not being a 0-negative donor and living in an urban area. Over time, hazards of becoming an inactive donor were converging for individuals living in non-urban and urban areas as were those of younger and older donors. After their first donation, 73·6% and 67·5% of males in the 1996–2002 and 2003–2008 cohorts, respectively, donated at least once in the following 24 months. The proportion of returning female donors was 71·8% and 65·4%, respectively. Conclusions The increased volatility of first-time blood donors suggests that marketing actions and strategies aimed at increasing return rates should be reinforced, especially for younger and female blood donors.

The impact of ABO incompatibility on hematopoietic stem cell transplantation (HSCT) outcome is controversial. As ABH substances are expressed on tissues and secreted in body fluids, they could drive an immune response in minor ABO-incompatible HSCT. The aim of the study was to investigate the prognostic role of the recipients' ABH secretor status.Patients who underwent minor ABO-incompatible HSCT were included. Secretor status was determined either serologically or by molecular genetics.Between March 1996 and June 2012, a total of 176 patients received minor ABO-incompatible HSCT and 150 (85%) were secretors. Incidence and severity of acute graft-versus-host disease (GVHD) and chronic GVHD did not differ between secretors and nonsecretors (cumulative incidences ± standard errors: acute GVHD on Day 100, 41 ± 11 and 46 ± 5%, p = 0.59; chronic GVHD at 2 years, 52 ± 13 and 56 ± 5%, p = 0.62, for secretors and nonsecretors, respectively). Additionally, nonrelapse mortality (NRM) and overall survival (OS) were similar in the two groups (2-year NRM, 27 ± 9 and 23 ± 3%, p = 0.45; 4-year OS, 64 ± 10 and 55 ± 4%, p = 0.28, for secretors and nonsecretors, respectively).The recipients' ABH secretor status in minor ABO-incompatible HSCT has no prognostic impact on major transplant outcomes.

Hyperferritinaemia is a frequent clinical problem. Elevated serum ferritin levels can be detected in different genetic and acquired diseases and can occur with or without anaemia. It is therefore important to determine whether hyperferritinaemia is due to iron overload or due to a secondary cause. The main causes of iron overload are intestinal iron hyperabsorption disorders and transfusion-dependent disorders. Iron homeostasis and iron overload are quantified by different diagnostic approaches. The evaluation of serum ferritin and transferrin saturation is the first diagnostic step to identify the cause of hyperferritinaemia. The assessment of liver iron concentration by liver biopsy or magnetic resonance imaging (MRI) may guide the further diagnostic and therapeutic workup. Liver biopsy is invasive and poorly accepted by patients and should only be carried out in selected patients with hereditary haemochromatosis. As a non-invasive approach, MRI is considered the standard method to diagnose and to monitor both hepatic iron overload and the effectiveness of iron chelation therapy in many clinical conditions such as thalassaemia and myelodysplastic syndromes. Accurate evaluation and monitoring of iron overload has major implications regarding adherence, quality of life and prognosis. There are different technical MRI approaches to measuring the liver iron content. Of these, T2 and T2* relaxometry are considered the standard of care. MRI with cardiac T2* mapping is also suitable for the assessment of cardiac iron. Currently there is no consensus which technique should be preferred. The choice depends on local availability and patient population. However, it is important to use the same MRI technique in subsequent visits in the same patient to get comparable results. Signal intensity ratio may be a good adjunct to R2 and R2* methods as it allows easy visual estimation of the liver iron concentration. In this review a group of Swiss haematologists and radiologists give an overview of different conditions leading to primary or secondary iron overload and on diagnostic methods to assess hyperferritinaemia with a focus on the role of liver MRI. They summarise the standard practice in Switzerland on the use of liver iron concentration MRI as well as disease-specific guideline recommendations.

Background The impact of ABO incompatibility on hematopoietic stem cell transplantation (HSCT) outcome is controversial. As ABH substances are expressed on tissues and secreted in body fluids, they could drive an immune response in minor ABO-incompatible HSCT. The aim of the study was to investigate the prognostic role of the recipients' ABH secretor status. Study Design and Methods Patients who underwent minor ABO-incompatible HSCT were included. Secretor status was determined either serologically or by molecular genetics. Results Between March 1996 and June 2012, a total of 176 patients received minor ABO-incompatible HSCT and 150 (85%) were secretors. Incidence and severity of acute graft-versus-host disease (GVHD) and chronic GVHD did not differ between secretors and nonsecretors (cumulative incidences ± standard errors: acute GVHD on Day 100, 41 ± 11 and 46 ± 5%, p = 0.59; chronic GVHD at 2 years, 52 ± 13 and 56 ± 5%, p = 0.62, for secretors and nonsecretors, respectively). Additionally, nonrelapse mortality (NRM) and overall survival (OS) were similar in the two groups (2-year NRM, 27 ± 9 and 23 ± 3%, p = 0.45; 4-year OS, 64 ± 10 and 55 ± 4%, p = 0.28, for secretors and nonsecretors, respectively). Conclusion The recipients' ABH secretor status in minor ABO-incompatible HSCT has no prognostic impact on major transplant outcomes.

Contexte La reduction des agents pathogenes par amotosalen/UVA (INTERCEPT™ (IA)) pour les concentres de plaquettes (CP) dont 80 a 90 % proviennent d’apherese, est utilisee en routine par notre institution. Les CP sont conserves pendant 7 jours maximums. Objectif Evaluer l’impact de la duree de conservation sur l’efficacite therapeutique des CP-IA pour les patients en hematologie-oncologie et ceux subissant une greffe de cellules souches hematopoietiques (GCSH) allogenique. Methodes Les increments plaquettaires (CI) et CI corriges (CCI) ont ete obtenus 1 a 4 heures apres la transfusion. Le risque d’echec de l’hemostase a ete evalue par la necessite d’une transfusion supplementaire de CP ou de concentres de globules rouges (CGR) le jour de la transfusion de CP ou le jour suivant. Resultats Voir Tableau 1 . De 2011 a 2016, 22578 CP ont ete transfuses a 2809 patients. 16,6 % des CP etaient âges de > 5 jours. Les GCSH representaient 14,8 % de la population (13,1 % allogreffes) et ont utilise 50,6 % des CP. La dose moyenne de plaquettes etait de 3,0 ± 0,4 × 10 11 , avec une duree de conservation moyenne de 4,1 ± 1,4 jours. Les CI et CCI ont diminue de facon lineaire avec l’âge des CP. L’utilisation de CP ou de CGR supplementaire(s) le jour meme ou le lendemain d’une transfusion de CP n’a pas augmente avec la duree de stockage. Le delai median avant la prochaine transfusion de CP (1,0 jour) n’etait pas affecte par la duree de conservation du CP. Conclusion L’augmentation de la duree de conservation des CP a ete associee a une diminution des CI et CCI mais n’affecte pas l’hemostase, comme en temoigne l’absence de besoin en CP ou de CGR supplementaires le jour meme ou suivant la transfusion de CP-IA.

Background and Objectives We describe the recognition and pattern of care of voluntary blood donors with early-uncomplicated genetic haemochromatosis in our blood donation centre. Materials and Methods Asymptomatic volunteers with suspicion of hereditary haemochromatosis (HH) due to an elevated ferritin level on routine screening were referred for further investigation. Alternatively, we accepted subjects with prediagnosed HH on referral. In the case of early-uncomplicated genetic haemochromatosis, either standard whole blood donation (WBD) or double-erythrocytapheresis (DEC) was offered. Results A median of six procedures was needed to achieve a ferritin value below 100 ng/ml in the WBD group and of four in the DEC group (P = 0·5). The rate of donation side-effects was higher in the DEC group, while the costs it generated were equivalent to WBD. Conclusion Compared with WBD, DEC had no beneficial effect on treatment number, length of treatment, side-effects or treatment budget in early-uncomplicated HH. Integrating donors with uncomplicated genetic haemochromatosis to blood donation programmes can supplement blood stores and provide the donors with a cost-effective and altruistic purpose of treatment.