Monitoring Blood Supply in Germany: A Regulatory Perspective.

Background and Objectives: A sufficient supply of safe, high-quality blood components for transfusion is essential to the healthcare system in Germany. The requirements for the current reporting system are laid down in the German Transfusion Act. The present work elaborates on the advantages and limitations of the current reporting system and investigates the feasibility of a pilot project that collects specific data on blood supply based on weekly reports. Materials and Methods: Selected data on blood collection and supply from 2009 to 2021 derived from the §21 German Transfusion Act database were examined. In addition, a pilot study over a period of 12 months was conducted on a voluntary basis. The number of red blood cell (RBC) concentrates was documented and stock availability was calculated weekly. Results: From 2009 to 2021, the annual number of RBC concentrates decreased from 4.68 to 3.43 million, the per capita distribution decreased from 58 to 41 RBC concentrates per 1,000 inhabitants. These figures did not change significantly during the COVID-19 pandemic. The data of the 1-year pilot project represented 77% of the released RBC concentrates in Germany. Percentage share of O RhD positive RBC concentrates fluctuated between 35% and 22% and for O RhD negative concentrates between 17% and 5%. The availability of O RhD positive RBC concentrate stocks varied between 2.1 and 7.6 days. Conclusion: The data presented shows a decrease in annual RBC concentrate sales over an 11-year period and no further change over the past 2 years. A weekly monitoring of blood components detects acute problems in RBC provision and supply. Close monitoring seems helpful but should be combined with a nationwide supply strategy.

Non-Invasive Zinc Protoporphyrin Screening Offers Opportunities for Secondary Prevention of Iron Deficiency in Blood Donors.

Background: Frequent blood donors are at high risk of developing iron deficiency. Currently, there is no potent screening during blood donation to detect iron deficient erythropoiesis (IDE) before anemia develops and deferral from donation is inevitable. Study Design and Methods: In addition to capillary and venous hemoglobin, the iron status of 99 frequent blood donors was assessed by various venous blood parameters and zinc protoporphyrin IX (ZnPP). ZnPP was determined by high-performance liquid chromatography (HPLC) and a new prototype fiber-optic device was employed for non-invasive measurements of ZnPP through the blood collection tubing (NI-tubing) and on lip tissue (NI-lip). We aimed to evaluate the feasibility and diagnostic value of the NI-tubing measurement for early detection of severe iron deficiency in blood donors. Results: NI-tubing and HPLC reference measurements of ZnPP showed narrow limits of agreement of 12.2 µmol ZnPP/mol heme and very high correlation (Spearman's Rho = 0.938). Using a cutoff of 65 µmol ZnPP/mol heme, NI-tubing measurements (n = 93) identified 100% of donors with iron deficiency anemia (IDA) and an additional 38% of donors with IDE. Accordingly, NI-tubing measurements would allow detection and selective protection of particularly vulnerable donors. Conclusion: NI-tubing measurements are an accurate and simple method to implement ZnPP determination into the routine blood donation process. ZnPP was able to identify the majority of subjects with IDE and IDA and might therefore be a valuable tool to provide qualified information to donors about dietary measures and adjustments of the donation interval and thereby help to prevent IDA and hemoglobin deferral in the future.

Deferral due to low hemoglobin and predictors of permanence in the blood donation system of repeat female blood donors.

OBJECTIVES: To evaluate the deferral rate due to low hemoglobin (Hb) in repeat female blood donors and identify the factors affecting their permanence in the blood donation system. MATERIALS AND METHODS: 8,368 repeat female blood donors who donated from January 2012 to December 2018 were included. Bivariate analysis and Kaplan-Meier curves were used to identify the covariates possibly associated with developing low Hb, and Cox proportional hazards modeling was used to adjust for all confounders. RESULTS: The global deferral rate due to low Hb was 2.4 %. According to baseline Hb, the frequency of low Hb was 0.7-4.1 %, and it was higher in platelet donors (5.8-9.1 %) than in whole blood donors (1.9 %). The main predictors were baseline Hb (compared to the first quartile; hazard ratio [HR] = 0.487 for the second quartile; 0.234 for the third; and 0.095 for the fourth); change in Hb (HR = 2.689 for a >0.49 g/dL change, compared to smaller changes); the type of donation (compared to whole blood donors, HR = 2.317 for platelet donors); and donation interval (compared to >12.5 month intervals; HR = 2.220 for 8.0-12.5 months; HR = 5.658 for 5.4-8.0 months; and HR = 9.452 for <5.4 months). CONCLUSIONS: In female blood donors at moderate altitude, the probability of developing low Hb increases with a baseline Hb of 13.5-14.0 g/dL, with a change in Hb >0.49 g/dL, in platelet donors, and with donation intervals <12.5 months. These four predictive factors can be used together for early identification of donors at risk of developing low Hb, to institute appropriate measures.

Head-to-head evaluation of seven different seroassays including direct viral neutralisation in a representative cohort for SARS-CoV-2.

A number of seroassays are available for SARS-CoV-2 testing; yet, head-to-head evaluations of different testing principles are limited, especially using raw values rather than categorical data. In addition, identifying correlates of protection is of utmost importance, and comparisons of available testing systems with functional assays, such as direct viral neutralisation, are needed.We analysed 6658 samples consisting of true-positives (n=193), true-negatives (n=1091), and specimens of unknown status (n=5374). For primary testing, we used Euroimmun-Anti-SARS-CoV-2-ELISA-IgA/IgG and Roche-Elecsys-Anti-SARS-CoV-2. Subsequently virus-neutralisation, GeneScriptcPass, VIRAMED-SARS-CoV-2-ViraChip, and Mikrogen-recomLine-SARS-CoV-2-IgG were applied for confirmatory testing. Statistical modelling generated optimised assay cut-off thresholds. Sensitivity of Euroimmun-anti-S1-IgA was 64.8%, specificity 93.3% (manufacturer's cut-off); for Euroimmun-anti-S1-IgG, sensitivity was 77.2/79.8% (manufacturer's/optimised cut-offs), specificity 98.0/97.8%; Roche-anti-N sensitivity was 85.5/88.6%, specificity 99.8/99.7%. In true-positives, mean and median Euroimmun-anti-S1-IgA and -IgG titres decreased 30/90 days after RT-PCR-positivity, Roche-anti-N titres decreased significantly later. Virus-neutralisation was 80.6% sensitive, 100.0% specific (≥1:5 dilution). Neutralisation surrogate tests (GeneScriptcPass, Mikrogen-recomLine-RBD) were >94.9% sensitive and >98.1% specific. Optimised cut-offs improved test performances of several tests. Confirmatory testing with virus-neutralisation might be complemented with GeneScriptcPassTM or recomLine-RBD for certain applications. Head-to-head comparisons given here aim to contribute to the refinement of testing strategies for individual and public health use.

Adding a piece to the puzzle of Latin American blood donors and the potential risk of Trypanosoma cruzi transmission in Germany.

Introduction: Chagas disease (CD) is caused by the Trypanosoma cruzi (T. cruzi) infection and has become a global health concern due to population mobility, as well as non-vectorial transmission routes. Several countries outside Latin America (LA) have reported transfusion-associated transmission, but equivalent studies in Germany are lacking. This study aims to collect first data on the risk of transfusion associated transmission as well as LA blood donors originating from CD endemic countries in Germany. Materials and methods: A total of 305 blood donors who were assumed to be at risk for T. cruzi infection were retrospectively (267) as well as prospectively (38) selected at German blood donation sites in Bavaria and Berlin, and all retrospectively as well as 27 prospectively selected were serologically screened. Prospective study subjects additionally filled out a questionnaire. Results: All samples tested seronegative for T. cuzi specific antibodies. Prospectively enrolled study subjects all had high socio-economic status including good education. Knowledge regarding CD was limited but willingness to donate frequently was high. Blood donation rates from donors born in LA countries seem to increase from 2015. Discussion: Although no transfusion associated T. cruzi infection has been documented in Germany, it has likely already happened unnoticed, or will do in the near future. Performing risk-adapted serology-based blood donor screenings in Germany could avoid transfusion-associated transmission events as well as contribute to active case detection. Moreover, larger, and ongoing studies are needed to increase the evidence base as well as end the neglect of CD in Germany.

Screening of platelet concentrates for bacterial contamination: spectrum of bacteria detected, proportion of transfused units, and clinical follow-up.

Screening of platelet concentrates (PCs) for bacterial contamination with cultivation methods is carried out as a routine procedure in some countries. The aim is to prevent the transfusion of contaminated PCs. The German Evaluation of Regular Monitoring Study Group conducted a prospective multicenter study on 52,243 PCs to investigate the prevalence of bacteria (BacT/ALERT, bioMerieux). This study describes the detected bacterial spectrum, the proportion of PCs with a positive test result that had been transfused, and the results of the clinical follow-up. One hundred thirteen (67%) of 169 potentially or confirmed positive units had already been transfused at the time of the first positive signal. The transfusion of units contaminated by Staphylococcus aureus, Serratia marcescens, and 73% of the units contaminated with Staphylococcus epidermidis, Staphylococcus capitis, or Staphylococcus saccharolyticus was prevented. In contrast, 85% of units with Propionibacterium acnes were transfused. A clonal relationship of the isolates from the pooled PCs and from the associated red blood cell concentrates was found in all investigated cases. The follow-up revealed six febrile reactions to culture-positive PCs not classified as transfusion reaction (TRs) by treating physicians. This demonstrates the importance of hemovigilance. Serious septic reactions due to Klebsiella pneumoniae in two units of one apheresis PC that had tested false-negative were reported; one had a fatal outcome. Culture systems reduce the risk of transfusion of contaminated PCs but cannot guarantee sterility. Physicians must be aware of bacterial contamination of PCs as a potential cause of TRs and must report all adverse events.

Supply with Platelet Concentrates from the Point of View of a Blood Donation Service of the Bavarian Red Cross.

SUMMARY: BACKGROUND: It is known that pooled platelet concentrates derived from buffy coat (PCs) have several disadvantages compared to platelet concentrates produced by platelet apheresis (APCs). Therefore, all blood products issued by the Bavarian Red Cross blood banks (BSD/BRK) (18,000 products/year) were produced by single donor apheresis. The main reason not to produce PCs was the elevated viral and bacterial infection risk during the last decade. But also the four-fold increased exposition to HLA and PLA antigens and the poor quality (in the sense of white and red cell contamination) of PCs (especially the ones produced with the platelet-rich plasma method) played a role to abstain from these products. MATERIAL AND METHODS: We performed a risk assessment to evaluate both products with regard to the actual testing and production methods, considering recently published data. However, a statistical calculation of the risks associated with the use of PCs or APCs with regard to different infectious agents with various prevalences was not done. RESULTS: The dramatically reduced risk for the transmission of HIV, HBV or HCV accompanying the implementation of improved antibody tests and of NAT minipool testing, the introduction of 100% leukocyte filtration, the conversion of PC production from the platelet-rich to the buffy coat method, and recent data on the risk of transmission of bacterial infections resulted in a equal assessment of APCs and PCs. CONCLUSION: As a consequence of this revised risk assessment, we supply our hospitals with both products APCs and buffy coat-derived PCs (pools of 4 donors). For clinical use we considered both products as equally effective, except for patients who have multiple antibodies and need HLA-typed platelets.

Bacterial contamination of platelet concentrates: results of a prospective multicenter study comparing pooled whole blood-derived platelets and apheresis platelets.

BACKGROUND: The GERMS Group initiated a prospective multicenter study to assess prevalence and nature of bacterial contamination of pooled buffy-coat platelet concentrates (PPCs) and apheresis platelet concentrates (APCs) by routine screening with a bacterial culture system. STUDY DESIGN AND METHODS: In nine centers overall, 52,243 platelet (PLT) concentrates (15,198 APCs, 37,045 PPCs) were analyzed by aerobic and anaerobic cultures (BacT/ALERT, bioMérieux). RESULTS: In 135 PLT concentrates (PCs; 0.26%), bacteria could be identified in the first culture (0.4% for APCs vs. 0.2% for PPCs; p < 0.001). In 37 (0.07%) of these PC units, the same bacteria strain could be identified in a second culture from the sample bag and/or the PC unit. The rate of confirmed-positive units did not differ significantly between APC (0.09%; 1/1169) and PPC units (0.06%; 1/1544). Bacteria from skin flora (Propionibacterium acnes, Staphylococcus epidermidis) were the most prevalent contaminants. Median times to first positive culture from start of incubation were 0.7 and 3.7 days in aerobic and anaerobic cultures for confirmed-positive units. With a "negative-to-date" issue strategy, most PC units (55%) had already been issued by time of the first positive culture. CONCLUSION: The rate of confirmed bacterial contamination of PC units was low. Nevertheless, clinicians must be aware of this risk. The risk of bacterial contamination does not warrant universal preference of APCs. It must be questioned whether routine bacterial screening by a culture method can sufficiently prevent contaminated products from being transfused due to the delay until a positive signal in the culture system and due to false-negative results.