RHD-negative red cells may be avoided for patients with ambiguous serologic typing for the RHD antigen.

BACKGROUND AND OBJECTIVES: Serologic typing with monoclonal anti-D is mandatory for RHD antigen determination before transfusion, but due to aberrant (weak or partial) variants of RHD, results may be ambiguous and molecular RHD-typing is required. Before that, RHD-negative (RHD -) red blood cells concentrates (RBCs) shall be transfused to avoid anti-D formation, which probably leads to wastage of RHD - RBCs. STUDY DESIGN AND METHODS: All patients with ambiguous results in serologic RHD-typing and molecular RHD-typing were assessed retrospectively. The proportions of patients at risk for anti-D formation and the proportion of RHD - RBCs transfused unnecessarily were evaluated for the following transfusion strategies: (1) RHD-positive (RHD + )RBCs for all patients, (2) RHD + RBCs for patients with at least 2+ reaction with anti-D, (3) RHD + RBCs for patients with C and/or E in their RHCE-phenotype, (4) RHD + RBCs for patients with C and/or E and at least 2+ reaction, and (5) RHD - RBCs for all patients. RESULTS: A total of 112 patients were included. Most had weak D type 1-3 and a minority had other, rare RHD variants. The risk of anti-D formation was 4.5%, 2.9%, 1.8%, 1.0%, and 0% for strategies 1-5, respectively. The proportion of RHD - RBCs transfused unnecessarily was 0%, 49.5%, 0.9%, 50.5%, and 95.5%. CONCLUSION: Transfusing patients with a C and/or E in their RHCE-phenotype with RHD + RBCs resulted in a very low risk of immunization while avoiding wastage of RHD - RBCs. Therefore, this strategy should be used for some patients with ambiguous results in serologic RHD-typing and pending results of molecular RHD-typing.

An international review of the characteristics of viral nucleic acid-amplification testing (NAT) reveals a trend towards the use of smaller pool sizes and individual donation NAT.

BACKGROUND AND OBJECTIVES: Nucleic acid-amplification testing (NAT) is used for screening blood donations/donors for blood-borne viruses. We reviewed global viral NAT characteristics and NAT-yield confirmatory testing used by blood operators. MATERIALS AND METHODS: NAT characteristics and NAT-yield confirmatory testing used during 2019 was surveyed internationally by the International Society of Blood Transfusion Working Party Transfusion-Transmitted Infectious Diseases. Reported characteristics are presented herein. RESULTS: NAT was mainly performed under government mandate. Human immunodeficiency virus (HIV), hepatitis C virus (HCV) and hepatitis B virus (HBV) NAT was performed on all donors and donation types, while selective testing was reported for West Nile virus, hepatitis E virus (HEV), and Zika virus. Individual donation NAT was used for HIV, HCV and HBV by ~50% of responders, while HEV was screened in mini-pools by 83% of responders performing HEV NAT. Confirmatory testing for NAT-yield samples was generally performed by NAT on a sample from the same donation or by NAT and serology on samples from the same donation and a follow-up sample. CONCLUSION: In the last decade, there has been a trend towards use of smaller pool sizes or individual donation NAT. We captured characteristics of NAT internationally in 2019 and provide insights into confirmatory testing approaches used for NAT-yields, potentially benefitting blood operators seeking to implement NAT.

International review of blood donation nucleic acid amplification testing.

BACKGROUND AND OBJECTIVES: Nucleic acid amplification testing (NAT), in blood services context, is used for the detection of viral and parasite nucleic acids to reduce transfusion-transmitted infections. This project reviewed NAT for screening blood donations globally. MATERIALS AND METHODS: A survey on NAT usage, developed by the International Society of Blood Transfusion Working Party on Transfusion-transmitted Infectious Diseases (ISBT WP-TTID), was distributed through ISBT WP-TTID members. Data were analysed using descriptive statistics. RESULTS: Forty-three responses were received from 32 countries. Increased adoption of blood donation viral screening by NAT was observed over the past decade. NAT-positive donations were detected for all viruses tested in 2019 (proportion of donations positive by NAT were 0.0099% for human immunodeficiency virus [HIV], 0.0063% for hepatitis C virus [HCV], 0.0247% for hepatitis B virus [HBV], 0.0323% for hepatitis E virus [HEV], 0.0014% for West Nile virus [WNV] and 0.00005% for Zika virus [ZIKV]). Globally, over 3100 NAT-positive donations were identified as NAT yield or solely by NAT in 2019 and over 22,000 since the introduction of NAT, with HBV accounting for over half. NAT-positivity rate was higher in first-time donors for all viruses tested except WNV. During 2019, a small number of participants performed NAT for parasites (Trypanosoma cruzi, Babesia spp., Plasmodium spp.). CONCLUSION: This survey captures current use of blood donation NAT globally. There has been increased NAT usage over the last decade. It is clear that NAT contributes to improving blood transfusion safety globally; however, there is a need to overcome economic barriers for regions/countries not performing NAT.

Serum reactivity in dermatitis herpetiformis: an international multicentre study.

BACKGROUND: Dermatitis herpetiformis (DH) is a rare gluten-induced skin disorder characterized predominantly by IgA autoantibodies against endomysium, tissue transglutaminase (TG2/tTG), epidermal transglutaminase (TG3/eTG) and deamidated gliadin. To date, circulating autoantibody reactivity has not been systematically described. OBJECTIVES: Characterization of serum reactivities in DH. METHODS: This multicentre international study analysed sera from 242 patients with DH taken at the time of initial diagnosis. DH-specific IgA and IgG serum autoantibodies were analysed by indirect immunofluorescence (IF) on monkey oesophagus, and by enzyme-linked immunosorbent assay (ELISA) based on recombinant TG2/tTG, TG3/eTG and deamidated gliadin (GAF3X). RESULTS: IgA indirect IF microscopy on monkey oesophagus revealed the highest reactivity (84.3%; specificity 100%) followed by IgA TG2/tTG ELISA (78.5%, specificity 99.0%), IgA TG3/eTG ELISA (72.7%, specificity 95.0%) and IgA GAF3X ELISA (69.0%, specificity 98.5%). CONCLUSIONS: Serum IgA and IgG autoantibodies against endomysium, TG2/tTG, TG3/eTG and deamidated gliadin are highly prevalent in DH. Indirect IF microscopy on monkey oesophagus (IgA) provides the highest diagnostic accuracy that can be further enhanced by 4.5% when combined with IgA TG2/tTG ELISA.

Validation of a predictive model for identifying an increased risk for recurrence in adolescents and young adults with a first provoked thromboembolism.

BACKGROUND: To develop and validate a predictive model to determinate patients at increased risk to suffer from recurrence following a first provoked deep vein thrombosis (VTE). METHODS: Predictive variables, i.e. male sex [1 point], inherited thrombophilia (IT) status (none [0 points], single [1 point], combined variants [2 points]), blood group non-0, and age at first VTE onset were included into a risk assessment model, which was derived in 511 patients and then validated in 509 independent subjects. RESULTS: VTE recurrence risk score (maximum 4 points, range 0-3) was below two for patients scored as low-risk (LRS) and ≥2 for patients at high-risk (HRS). Within a median time of 3 years after withdrawal of anticoagulation (AC) recurrence rate in LRG (derivation) was 11.8% versus 26.0% in HRS (p < 0.001). In the validation cohort within 2.2 years the recurrence rate was 9.8% in LRS versus 30.1% in HRS (p < 0.001). In multivariable analysis adjusted for age at first VTE and blood group the recurrent risk in HRS was significantly increased compared with the LRS (derivation: hazard/95% confidence interval: 3.7/1.75-7.91; validation: 4.7/2.24-9.81; combined 5.2/1.92-13.9). Model specificity (sensitivity) was 79.0% (52.0%) in the derivation cohort compared with 78.0% (43.0%) in the validation group. In conclusion, in the prediction model presented here the risk of VTE recurrence was associated with male gender and combined ITs. Based on the negative predictive value calculated the model may identify patients with a first provoked VTE not being at risk for recurrence.

Completing the Donor History Questionnaire before the Donation Visit Can Improve Blood Safety.

Background and Objectives: In Germany, the donor history questionnaire (DHQ) is traditionally filled in at the donation center to avoid any influence of others. Since March 2020, it has been suggested to donors to answer the DHQ already at home and to call if they have any concerns to reduce the number of ineligible donors on-site during the COVID-19 pandemic. Materials and Methods: We evaluated the rate of ineligible donors before and after March 2020. Additionally, an anonymous online survey asking for the donors' attitude towards the DHQ was performed. It included questions on whether and for what reason the DHQ had been answered incorrectly in the past. Results: The rate of ineligible donors decreased by 27% (from 7.1% to 5.2%). In total, 5,556 of 10,252 invited donors completed the survey (54.2%). 88.6% reported either going through the DHQ at home or knowing all questions from their previous donations. 444 donors (8.0%) had at least once postponed a donation after reading the DHQ at home. 68 donors (1.2%) admitted having intentionally provided false answers in the past (9 at home, 43 on-site, 14 both, 2 unknown). Not wanting to be rejected once arriving at the donation center was an important motivation for 42% of donors answering incorrectly on-site. Details on 46 incorrect answers were provided: only 17 had no influence on donor eligibility or product quality. In 5 cases, some blood products might have had impaired quality. Truthful answers to 17 questions would have led to deferral, mostly due to increased risk for unrecognized viral infections transmitted by sexual contacts. For a further 7 questions, there was insufficient information available to determine possible consequences. Asked about their general opinion, 753 (13.6%) of all donors estimated the risk of incorrect answers being greater on-site, while 239 (4.3%) presumed an increased risk at home. Conclusion: Answering the DHQ prior to a donation visit prevented ineligible donors from visiting the donation center. Furthermore, it might improve honesty, as the discomfort of being deferred after arriving at the donation center was an important reason to answer incorrectly. Overall, there was no increased risk of donor or product safety, and potentially even a benefit.

Acquired von Willebrand syndrome in ECMO patients: A 3-year cohort study.

BACKGROUND: Bleeding is a common but possibly underreported side effect of Extracorporeal Membrane Oxygenation (ECMO). Impairment of primary hemostasis by acquired von Willebrand syndrome (aVWS) and platelet dysfunction as well as activation and consumption of plasmatic coagulation factors contribute to hemorrhage. The aim of the present cohort study of consecutively enrolled patients admitted to our ECMO center was to collect demographic, medical and laboratory data possibly associated with i) development of clinically relevant bleeding and/or ii) death during a 12-months follow-up. RESULTS: Within a 3-year period 338 white patients aged 18-89 years (median: 60; male 64.5%) were enrolled. 78 of 338 patients (23%) presented with clinical relevant bleeding symptoms. The overall death rate was 74.6% within a median time of 9 days (1-229) post intervention. Logistic-regression analysis adjusted for age and gender revealed that i) the presence of blood group O versus non-O (Odds ratio (OR)/95%CI: 1.9/1.007-3.41), ECMO duration per day (1.1/1.06-1.14), veno-venous versus veno-arterial ECMO cannulation (2.33/1.2-4.5) and the overall need for blood product administered per unit (1.02/1.016-1.028) was independenly associated with bleeding in patients suffering from aVWS. ii) Older age (increase per year) at ECMO start (1.015/1.012-1.029) and an increasing amount of blood product units were significantly related with death (1.007/1.001-1.013). Patients with veno-venous versus veno-arterial cannulation survived longer (0.48/0.24-0.94). CONCLUSION: In the present cohort study we found a clinical relevant bleeding rate of 23% in subjects with aVWS associated with blood group O, a longer ECMO duration and veno-venous cannulation.

Two Novel Variants in the Protein S Gene PROS1 Are Associated with Protein S Deficiency and Thrombophilia.

Protein S (PS) is an important anticoagulant. Its main function is to act as a non-enzymatical cofactor of activated protein C. PS deficiency is defined as low plasma levels of PS and/or loss of function associated with variable risk of venous thromboembolism (VTE). We report 2 novel variants in the PS gene (PROS1) which are associated with PS deficiency and severe thrombophilic diathesis in 2 patients. Patient 1 suffered from 3 VTE events, including a spontaneous VTE at the age of 19. Patient 2 suffered from 2 provoked VTE events. In both patients decreased plasma levels of PS antigen as well as decreased PS activity were found. Gene sequencing results showed a heterozygous deletion of 8 base pairs (c.938_945delTAAAATTT, p.Leu313Serfs13*) in exon 9 of the PROS1 gene in patient 1 and a missense variant (c.1613C>T, p.Ser538Phe) in patient 2. Due to the clinically proven history of recurrent VTE events in both patients, genetic testing of first-degree relatives is discussed.

Role of prothrombin 19911 A>G polymorphism, blood group and male gender in patients with venous thromboembolism: Results of a German cohort study.

The role of the A>G polymorphism at position 19911 in the prothrombin gene (factor [F] 2 at rs3136516) as a risk factor for venous thromboembolism [VTE] is still unclear. To evaluate the presence of the F2 polymorphism in VTE patients compared to healthy blood donors and to adjust the results for common inherited thrombophilias [IT], age at onset and blood group [BG], and to calculate the risk of VTE recurrence. We investigated 1012 Caucasian patients with a diagnosis of VTE for the presence of the F2 rs3136516 polymorphism and compared these with 902 healthy blood donors. Odds ratios [OR] together with their 95% confidence intervals were calculated adjusted for F5 at rs6025, F2 at rs1799963, blood group, age and gender. In addition, we evaluated the risk of recurrent VTE during patient follow-up calculating hazard ratios [HR] together with their 95% CI. Compared with the AA wildtype, the F2 GG and AG genotypes (rs3136516) were associated with VTE (OR 1.48 and 1.45). The OR in F5 carriers compared to controls was 5.68 and 2.38 in patients with F2 (rs1799963). BG "non-O" was significantly more often diagnosed in patients compared to BG "O" (OR 2.74). VTE recurrence more often occurred in males (HR 2.3) and in carriers with combined thrombophilia (HR 2.11). Noteworthy, the rs3136516 polymorphism alone was not associated significantly with recurrence. In Caucasian patients with VTE the F2 GG/GA genotypes (rs3136516) were moderate risk factors for VTE. Recurrence was associated with male gender and combined thrombophilia.

Donors for SARS-CoV-2 Convalescent Plasma for a Controlled Clinical Trial: Donor Characteristics, Content and Time Course of SARS-CoV-2 Neutralizing Antibodies.

BACKGROUND: Convalescent plasma is one of the treatment options for COVID-19 which is currently being investigated in many clinical trials. Understanding of donor and product characteristics is important for optimization of convalescent plasma. METHODS: Patients who had recovered from CO-VID-19 were recruited as donors for COVID-19 convalescent plasma (CCP) for a randomized clinical trial of CCP for treatment of severe COVID-19 (CAPSID Trial). Titers of neutralizing antibodies were measured by a plaque-reduction neutralization test (PRNT). Correlation of antibody titers with host factors and evolution of neutralizing antibody titers over time in repeat donors were analysed. RESULTS: A series of 144 donors (41% females, 59% males; median age 40 years) underwent 319 plasmapheresis procedures providing a median collection volume of 850 mL and a mean number of 2.7 therapeutic units per plasmapheresis. The majority of donors had a mild or moderate course of COVID-19. The titers of neutralizing antibodies varied greatly between CCP donors (from <1:20 to >1:640). Donor factors (gender, age, ABO type, body weight) did not correlate significantly with the titer of neutralizing antibodies. We observed a significant positive correlation of neutralization titers with the number of reported COVID-19 symptoms and with the time from SARS-CoV-2 diagnosis to plasmapheresis. Neutralizing antibody levels were stable or increased over time in 58% of repeat CCP donors. Mean titers of neutralizing antibodies of first donation and last donation of repeat CCP donors did not differ significantly (1:86 at first compared to 1:87 at the last donation). There was a significant correlation of neutralizing antibodies measured by PRNT and anti-SARS-CoV-2 IgG and IgA antibodies which were measured by ELISA. CCP donations with an anti-SARS-CoV-2 IgG antibody content above the 25th percentile were substantially enriched for CCP donations with higher neutralizing antibody levels. CONCLUSION: We demonstrate the feasibility of collection of a large number of CCP products under a harmonized protocol for a randomized clinical trial. Titers of neutralizing antibodies were stable or increased over time in a subgroup of repeat donors. A history of higher number of COVID-19 symptoms and higher levels of anti-SARS-CoV-2 IgG and IgA antibodies in immunoassays can preselect donations with higher neutralizing capacity.

Prevalence of antibodies against Hepatitis D virus (HDV) in blood donors in Northern Germany.

OBJECTIVE: To assess the prevalence of HDV infections in German blood donors. METHOD: 167 donors with acute/chronic or resolved HBV infection and detectable antibodies against Hepatitis B core antigen (anti-HBc) were tested for antibodies against HDV (anti-HDV) by competitive ELISA. Samples with detectable anti-HDV or with HBsAg and/or HBV DNA were additionally investigated for HDV RNA. RESULTS: In nine (5.4 %) of the 167 donors, also HBsAg and HBV DNA were detectable. Anti-HDV was detectable in two of the 167 donors (1.2 %), additional four donors (2.4 %) had a borderline result. All of these donors tested negative for HBsAg and HBV DNA. Neither in samples with anti-HDV nor in HBsAg-/HBV DNA-positive samples, HDV RNA was detectable. CONCLUSIONS: At least 1.2 % of anti-HBc-positive blood donors have had an HDV infection. Although there is some evidence for a somewhat higher prevalence of HDV, the overall prevalence of HDV in Northern Germany is low.

Impacts of platelet-rich fibrin and platelet-rich plasma on primary osteoblast adhesion onto titanium implants in a bisphosphonate in vitro model.

BACKGROUND: Osteoblast adhesion is a crucial step in osseointegration of dental implants and can be influenced by modification of implant surface or the addition of bioactive agents. Bisphosphonates affect bone turnover, attenuating bone healing in implants patients. PRP and PRF are sources of growth factors involved in osteoblast adhesion, improving subsequent bone healing. The aim of the study was to investigate the impacts of PRP and PRF on adhesion of bisphosphonate-pretreated osteoblasts on titanium implant surfaces using the cell-count wash assay, the MTT-assay as well as real-time-cell analyser assay and scanning electronic microscopy. METHODS: Titanium implants were colonised for 24 hours with osteoblasts and zolendronic acid, PRP or PRF in different combinations. Afterwards, primary osteoblast adhesion was evaluated by counting the number of attached cells using a wash-assay cell analysis. Scanning electronic microscopy was performed and evaluated semi-quantitatively to assess the influence of the different groups on the ultrastructural cell morphology, such as cell size and shape as well as length and number of filopodia. RESULTS: Zoledronic acid led to a decrease of osteoblast adherence onto implant surface. This effect was reversed by adding PRP or PRF. Scanning electronic microscopy showed that both PRP and PRF increased number and length of filopodia in adherent osteoblasts. CONCLUSIONS: Zoledronic acid decreased osteoblast adhesion on implant surfaces, and PRF as well as PRP increased primary adhesion of zoledronic acid-treated osteoblasts on implant surfaces in vitro. Therefore, PRP and PRF may improve initial bone apposition and primary healing of dental implants in patients with bisphosphonate treatment.

Health-related quality of life in children, adolescents and adults with hereditary and acquired bleeding disorders.

BACKGROUND: To better understand self-reported health-related quality-of-life (HrQoL) in children and adults with chronic hemostatic conditions compared with healthy controls. METHODS/PATIENTS/RESULTS: Group 1 consisted of 74 children/adolescents aged 8-18years with hereditary bleeding disorders (H-BD), 12 siblings and 34 peers. Group 2 consisted of 82 adult patients with hereditary/acquired bleeding disorders (H/A-BD), and group 3 of 198 patients with deep venous thrombosis (DVT) on anticoagulant therapy. Adult patients were compared to 1011 healthy blood donors. HrQoL was assessed with a 'revised KINDer Lebensqualitaetsfragebogen' (KINDL-R)-questionnaire adapted to adolescents and adults. No differences were found in multivariate analyses of self-reported HrQoL in children with H-BD. In contrast, apart from family and school-/work-related wellbeing in female patients with DVT the adult patients showed significantly lower HrQoL sub-dimensions compared to heathy control subjects. Furthermore, adults with H/A-BD disorders reported better friend-related HrQoL compared to patients with DVT, mainly due to a decreased HrQoL subscale in women on anticoagulation. CONCLUSION: In children with H-BD, HrQoL was comparable to siblings and peers. In adults with H/A-BD HrQoL was comparable to patients with DVT while healthy blood donors showed better HrQoL. The friend-related HrQoL subscale was significantly reduced in female compared to male patients.

Infectivity of blood products containing cytomegalovirus DNA: results of a lookback study in nonimmunocompromised patients.

BACKGROUND: DNA of human cytomegalovirus (CMV) is frequently detected in plasma of donors with primary CMV infection. It is unknown, however, whether leukoreduced blood products from these donors contain sufficient amounts of infectious virus to cause transfusion-transmitted CMV infections (TT-CMV). STUDY DESIGN AND METHODS: During a 14-year period, CMV DNA-positive donations were identified as part of several previously published studies. Additionally, further donors with seroconversion were tested for CMV DNA. The serostatus of patients who had received a CMV DNA-positive blood product was determined out of pretransfusion samples. Later samples were examined for development of CMV antibodies. Patients with a follow-up of less than 140 days were also tested for CMV DNA. RESULTS: A total of 221 blood products from CMV DNA-positive donations were transfused to 219 recipients. Pretransfusion samples were available for 179 patients, of whom 62 (34.6%) were seronegative. For 39 seronegative recipients of 40 blood products follow-up samples drawn at least 30 days after transfusion were available. The median duration of follow-up was 287 days (range, 38-3784 days). Thirty-six patients were still CMV seronegative in their last sample. Three patients were CMV seropositive due to passive antibody transfer by plasma rich products from seropositive donors, but CMV DNA negative in all tested samples. CONCLUSION: TT-CMV was excluded in all recipients of 40 blood products from CMV DNA-positive donations. This corresponds to a 95% interval of confidence for the risk of TT-CMV of less than 7.4%. Because no patient belonged to a typical at-risk population, the results are only valid for immunocompetent subjects.

Cytomegalovirus Serostatus as Predictor for Adverse Events After Cardiac Surgery: A Prospective Observational Study.

OBJECTIVE: To clarify whether reactivated cytomegalovirus (CMV) infections in critically ill patients lead to worse outcome or just identify more severely ill patients. If CMV has a pathogenic role, latently infected (CMV-seropositive) patients should have worse outcome than seronegative patients because only seropositive patients can experience a CMV reactivation. DESIGN: Post-hoc analysis of a prospective observational study. SETTING: Single university hospital. PARTICIPANTS: The study comprised 983 consecutive patients scheduled for on-pump surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: CMV antibodies were analyzed in preoperative plasma samples. Postoperative adverse events (reintubation, low cardiac output or reinfarction, dialysis, stroke) and 30-day and 1-year mortality were evaluated prospectively. The plasma of reintubated patients and matched control patients was tested for CMV deoxyribonucleic acid, and 618 patients were found to be seropositive for CMV (63%). Among these, the risk for reintubation was increased (10% v 4%, p = 0.001). This increase remained significant after correction for confounding factors (odds ratio 2.70, p = 0.003) and was detectable from the third postoperative day throughout the whole postoperative period. Other outcome parameters were not different. Reintubated seropositive patients were more frequently CMV deoxyribonucleic acid-positive than were matched control patients (40% v 8%, p<0.001). CONCLUSIONS: CMV-seropositive patients had an increased risk of reintubation after cardiac surgery, which was associated with reactivations of their CMV infections. Additional studies should determine whether this complication may be prevented by monitoring of latently infected patients and administering antiviral treatment for reactivated CMV infections.

Comparison of Two Test Strategies for Clarification of Reactive Results for Anti-HBc in Blood Donors.

OBJECTIVE: Testing for antibodies against hepatitis B core antigen (anti-HBc) was introduced to detect blood donors suffering from occult hepatitis B infection. Confirmation of specification of reactive results in the anti-HBc screening assay is still a challenge for blood donation services. METHODS: Two different test strategies for confirmation of specification of reactive anti-HBc tests, one performed in our institute and one suggested by the German authority (Paul-Ehrlich-Institut (PEI)), were compared. The first strategy is based on one supplemental anti-HBc test, the other requires two supplemental anti-HBc tests. RESULTS: 389 samples from 242 donors were considered. Both test strategies yielded concordant results in 117 reactive samples termed 'true-positive' or 'specificity confirmed', in 156 reactive samples termed 'false-positive' or 'specificity not confirmed', and in 99 negative samples. In 17 samples obtained from 11 donors, both test strategies gave discrepant results ('false-positive' but 'specificity confirmed'). In 10 of 11 donors, a real HBV infection was very unlikely, one remained unclear. 30 donors considered 'false-positive' became negative in all anti-HBc tests after follow-up testing and thus eligible for donor re-entry. CONCLUSIONS: The test strategy suggested by the PEI yielded no additional information but induced an overestimation of HBV infections and unnecessary look-back procedures. Many anti-HBc-reactive donors can be regained after follow-up testing.

Co-occurrence of autoantibodies in healthy blood donors.

Autoimmune diseases are rare, but their incidence has increased over the past decades. Interestingly, the co-occurrence of autoimmune diseases is well documented; however, data on the presence of more than one specific autoantibody in healthy individuals are not available. Here, we investigated the prevalence of several autoantibodies in a cohort of over 6000 healthy persons. While individual autoantibodies were rarely detected (i.e. ranging from 0.3% for ANCA to 4.6% for anti-TPO), the cumulative prevalence of the tested autoantibodies was as high as 10%. Furthermore, our results demonstrate co-occurrence of ANA with specific autoantibodies that target TPO, CCP and Dsg1/3, while ANCA and autoantibodies to PCA and BP180/BP230 were not more frequent in ANA-positive compared to ANA-negative samples. This indicates that shared and independent mechanisms influence loss of tolerance to distinct sets of self-antigens.

Seroprevalence and incidence of hepatitis E virus infection in German blood donors.

BACKGROUND: Hepatitis E virus (HEV) is transmissible by transfusion. More data are needed about seroprevalence, incidence, and viremia in blood donors for the assessment of risk of transfusion-transmitted (TT)-HEV infections. STUDY DESIGN AND METHODS: Samples from 1019 whole blood donors were tested for anti-HEV immunoglobulin (Ig)G by enzyme-linked immunosorbent assay and Western blot. The incidence of HEV and presence of HEV RNA in donors who seroconverted were determined by testing archive samples and recipients of viremic donations were traced. Anti-HEV IgM and alanine transaminase (ALT) testing were also performed to assess the value of such measures in the prevention of TT-HEV infections. RESULTS: A total of 69 of 1019 donors tested positive for anti-HEV IgG (6.8% seroprevalence), and seroconversion for anti-HEV IgG occurred in seven of 69 donors within 2 years (incidence, 0.35%/year). Three of seven (42.8%) seroconverting donors provided an archive sample in which HEV RNA was detectable. One recipient of these donations was traceable; anti-HEV IgG, IgM, and HEV RNA testing were negative 41 days after transfusion. Neither ALT levels nor anti-HEV IgM detection correlated with the presence of HEV RNA. CONCLUSIONS: The seroprevalence of HEV was 6.8%, and the annual incidence 0.35%. HEV RNA was detectable in several seroconverting donors, without evidence for HEV transmission in the only traceable recipient. Since neither ALT nor anti-HEV IgM testing correlate with the presence of HEV RNA, HEV nucleic acid testing currently provides the only method for the prevention of TT-HEV infection. However, before implementation, more data about clinical relevance of TT-HEV infections and infectious dose of HEV are required.