A national surveillance system for continuous monitoring of blood transfusion safety: German haemovigilance data.

BACKGROUND AND OBJECTIVES: Haemovigilance (HV) systems aim to improve transfusion outcomes in patients and donor safety. An important question for blood regulators is how to ensure an effective HV system. MATERIALS AND METHODS: We retrospectively analysed the HV reports submitted to Paul-Ehrlich-Institut over the last two decades. RESULTS: Between 2011 and 2020, 50.86 million units of blood components were used, and 8931 suspected serious donor and recipient adverse reactions (SARs), 874 serious adverse events (SAEs) and 12,073 donor look-backs were reported. Following implementation of specific risk-minimization measures (RMMs) between 2000 and 2010, SAR reporting rates decreased for transfusion-transmitted viral infections (TTVIs), transfusion-related acute lung injury (TRALI) and transfusion-transmitted bacterial infections (TTBIs), while increasing for other serious adverse transfusion reactions. Within this decade, the overall blood component use decreased. CONCLUSION: Long-term data collection forms the basis to establish trends and changes in reporting and to evaluate the effect of RMM. Standardized criteria for reaction types, seriousness and imputability assessments and availability of a denominator are important elements. Central data collection and independent assessment allow for monitoring HV data in a nationwide context over time. Stakeholder involvement and transparent feedback on the benefit of RMM will help to achieve the objectives of HV.

Analysis of Transfusion-Transmitted Bacterial Infections according to German Hemovigilance Data (2011-2020).

Introduction: Following the first assessment of the effects of safety measures taken against transfusion-transmitted bacterial infections (TTBI), the Paul-Ehrlich-Institut (PEI) decided to newly analyze risk minimization measures (RMM) using German hemovigilance data from 2011 to 2020, focusing on blood components, recipients, and bacterial strains. Materials and Methods: The PEI assessed the imputability of all reported serious adverse reactions (SAR) relying mainly on microbiological test results. Reporting rates (RR) of suspected, confirmed, and fatal confirmed TTBI were calculated and compared to the previous reporting 10-year period (2001-2010) using Poisson regression to estimate RR ratios (RRR). Furthermore, details on blood component age, patients' medical history, and bacterial pathogenicity were collected. Results: With respect to the previous 10-year period, the number of suspected TTBI increased (n = 403), while fewer cases were confirmed (n = 40); the number of deaths remained more or less unchanged (n = 8). The RR for suspected TTBI were 7.9, 18.7, and 1.6 cases per million units transfused for red blood cells (RBC), platelet concentrates (PC), and fresh frozen plasma (FFP), respectively. RRR showed a statistically significant 2.5-fold increase in the RR for suspected TTBI after RBC administration from 2001-2010 to the period under review (p < 0.0001). The RR for confirmed TTBI were 0.4, 5.0, and 0.0 cases per million units transfused for RBC, PC, and FFP, respectively. Compared to the period 2001-2010, there was a statistically significant decrease in the RR of confirmed TTBI by half for PC (p = 0.0052). The RR for confirmed PC-caused TTBI with fatal outcome was 1.4 cases per million units transfused. Regardless of type of blood product transfused and outcome of SAR, the majority of TTBI occurred after administration of a product at the end of shelf life (40.0%) and to recipients of advanced age (median age: 68.5 years) and/or with severe immunosuppression (72.5%) due to decreased myelopoiesis (62.5%). 72.5% of the involved bacteria had a middle/high human pathogenicity. Conclusion: Despite a significant decrease in confirmed TTBI following PC transfusion in Germany after implementation of RMM, the current manufacture of blood products can still not prevent TTBI with fatal outcomes. As demonstrated in various countries, RMM like bacterial screening or pathogen reduction may measurably improve the safety of blood transfusion.

Follow-Up of Plasma Donors after Quarantine Storage: Results of a 5-Year Survey in Germany.

Background and Objectives: In 1993, a quarantine storage of 6 months was introduced for plasma for transfusion and was reduced to 4 months in 2003, owing to the improvements of screening assays used in German blood establishments. The presented survey analyses the value of quarantine storage under the current screening conditions. Materials and Methods: From 2015 to 2019, we collected data on the total amount of released quarantine plasma as well as on the number of quarantine plasma not released due to a reactive screening test of a follow-up donation. Results: Responding establishments covered 84% of plasma units released within the sampled period. In 3,583,913 (99.98%) of the total 3,584,664 test pairs, all screening assays revealed a negative result, leading to plasma release from quarantine storage. In 442 out of the residual 751 cases, confirmed positive results for human immunodeficiency virus (24), hepatitis C virus (22), or hepatitis B virus (396) were obtained in the follow-up donations. Of them, 372 revealed negative ID-NAT results in their retain samples confirmed by using highly sensitive individual donor nucleic acid amplification technology. In 70 cases, no testing of retain samples was performed as plasma was released for fractionation. The maximum theoretical risk for an undetected human immunodeficiency virus, hepatitis C or B virus infection was less than 0.0001%. Conclusion: No positive donation were found under the current screening regime and the quarantine storage during the 5-year survey period. In view of the current type and sensitivity of screening tests in German blood establishments, the results allow a reassessment of the value of quarantine storage of plasma regarding duration and release modalities. Due to the more sensitive donor screening, shorter quarantine periods as well as dispensing quarantine storage can be discussed. A reduction in the safety standard of plasma transfusions need not be feared, and the availability of plasma for transfusions could be facilitated.

Blood Donation-Related Adverse Reactions: Results of an Online Survey among Donors in Germany (2018).

INTRODUCTION: According to German legislation, reports of suspected serious adverse reactions (AR) associated with the donation of blood and its components are continuously being evaluated by the Paul-Ehrlich-Institut. This survey aimed at providing a more complete picture of the AR associated with the donation of blood and blood components. MATERIALS AND METHODS: Eligible donors had the opportunity to anonymously report all AR occurring during or after their last donation by completing an online questionnaire. Reported AR were classified according to the Standard for Surveillance of Complications Related to Blood Donation. Donors' self-assessment of AR seriousness was compared with the official severity classification as laid down by German legislation. Besides a descriptive statistical analysis, a multiple logistic analysis was performed to identify risk factors for AR. RESULTS: A total of 8,138 data records were evaluated. Slightly more males (57.9%) participated in the survey and, except for donors aged ≥60 years, all age groups were equally represented. The majority of participants were whole blood donors (85.4%), repeat donors (97.2%), and stayed under observation in the blood establishment (BE) for more than 5 min (63.1%) after donation. Most participants did not report any reaction (72.5%), whereas 2,237 reported at least one AR (27.5%), 475 of whom underwent apheresis and 1,762 donated whole blood. Most AR occurred after leaving the BE (64.4%). Only a minority of participants required medical treatment (5.1%) or assessed the experienced AR as serious (3.9%). The most frequently reported donor AR were haematoma and other local reactions (57.6%). Vasovagal reactions without and with loss of consciousness were developed in 17 and 2% of the participants, respectively, whilst 7.6% experienced citrate reactions. New AR (i.e., allergic reactions and symptoms associated with iron deficiency) were reported as well. The occurrence of AR was linked to risk factors (i.e., female gender, young age, first-time donation, and thrombocytapheresis). DISCUSSION: This survey yielded a more comprehensive AR spectrum, revealed a prolonged time to symptom onset, and identified risk factors for AR. This novel information could be implemented in an amended informed consent addressing common and rare AR.

Detection of hepatitis B virus infection in German blood donors 2008-2015.

BACKGROUND AND OBJECTIVES: Assessment of HBV-NAT testing compared to HBsAg and anti-HBc screening in German blood establishments for the period 2008-2015. MATERIALS AND METHODS: Blood donations screened for HBsAg and anti-HBc along with HBV-NAT were evaluated. Sensitivity of HBsAg and HBV-NAT tests was compared in 30 HBV seroconversion panels and with the viral load of the NAT-only cases. Residual risk for HBV in the WP was modelled. RESULTS: A total of 45 270 111 donations were evaluated. There were 29 NAT-only cases in the HBsAg-negative HBV-WP, one by ID-NAT and 28 by MP-NAT. MP-NAT, on average, showed higher sensitivity than HBsAg testing: MP-NAT-LoD of 146 IU/ml vs. 362 IU/ml HBV DNA for positive HBsAg detection (range 135-1502 IU/ml), resulting in 3·1 days (range 2·0-4·8 days) earlier HBV detection. Viral loads of the NAT-only cases confirmed the sensitivity of the HBV tests in the seroconversion study. One HBsAg-negative case was due to a new HBsAg mutant combination. There was one HBsAg-reactive only case. In addition, HBV incidence in the HBV-WP included 41 HBsAg-/HBV-NAT-positives and three HBV transmission cases. The residual risk for HBsAg was estimated to be 1:1 619 419-1 268 474 compared to 1:2 793 365-2 134 702 for MP-NAT. Within chronic HBV (HBsAg-/anti-HBc-positive and MP-NAT-negative) 70% were ID-NAT positive at low viral load (median 20 IU/ml). Among anti-HBc-only, supplementary ID-NAT detected 23 occult HBV infections. CONCLUSIONS: In the HBV-WP, MP-NAT provided a higher sensitivity than HBsAg testing, obtained a considerably higher yield and reduced the risk for HBV transmission. In later HBV stages, anti-HBc screening and HBV-ID-NAT intercepted potentially infectious donations.

Effectiveness of blood donor screening by HIV, HCV, HBV-NAT assays, as well as HBsAg and anti-HBc immunoassays in Germany (2008-2015).

BACKGROUND AND OBJECTIVES: In Germany, in addition to standard blood donor screening, further mandatory tests were introduced for HCV-RNA, HIV-1-RNA and for anti-HBc. Screening for HBV-DNA is optional. This study investigates the benefits of these additional tests for the detection of HIV, HCV, and HBV infections among German blood donors. MATERIALS AND METHODS: From 2008 to 2015 we collected data on blood donations exclusively testing NAT positive (NAT yield) or reactive in only one of the screening assays. Assuming a Poisson distribution, we calculated NAT yield/reactive only rates on a per donation basis (number of yield/reactive only cases divided by the number of donations tested in the period under review) with 95% confidence intervals. RESULTS: Responding establishments covered 95% of the donations. We identified 20 HIV-1-NAT, 61 HCV-NAT and 29 HBV-NAT yield cases among approximately 46 million blood donations tested corresponding to 0·43 HIV-1 NAT, 1·32 HCV-NAT, and 0·64 HBV-NAT yield cases per million blood donations tested. For one HBsAg reactive only case and 23 anti-HBc reactive only cases in repeat donors, infection was confirmed by ID-NAT which translates into 0·02 and 0·55 cases per million donations tested. During the 8-year-observation period, one HIV-1, no HCV and four HBV transmissions associated with donations in the viremic pre-seroconversion window period were reported. CONCLUSION: Annually, NAT screening alone detected 2·5 HIV-1, 7·6 HCV, and 3·6 HBV infectious donations; anti-HBc screening alone identified 2·9 infectious donations of repeat donors with occult HBV infection. Overall, the survey results support that the currently practiced donor HIV/HCV/HBV screening strategy in Germany does ensure a high standard of blood safety.

Impact of hepatitis E virus testing on the safety of blood components in Germany - results of a simulation study.

Hepatitis E virus (HEV) infections may be acquired through transfusion of blood components. As transfusion-transmitted infections mostly affect vulnerable individuals, measures to ensure the supply of safe blood components are under discussion. On the basis of the epidemiological situation in Germany, different testing strategy scenarios were investigated through simulation studies. Testing for HEV RNA by nucleic acid amplification technique (NAT) assays with a pool size of 96, and a 95% LoD of 20 IU/ml will result in an 80% reduction in expected HEV transmissions as well as of consequent chronic infections with subsequent severe complications.

Selecting the Right Donors - Still a Challenge: Development of a Uniform Donor Questionnaire in Germany.

The selection of blood donors includes the assessment of the individual's health and medical history by using a donor questionnaire (DQ) in order to identify persons whose donation could present a health risk to recipients or to themselves. This way, DQs provide one layer of blood safety and contribute to the high safety profile of blood components currently available in Germany. This review reports the development of a new uniform questionnaire in Germany and its first evaluation using a field test approach. This development is set in context with the international experiences regarding donor selection and prospective challenges.

Good Feasibility of the New German Blood Donor Questionnaire.

BACKGROUND: We assessed the effect of the uniform donor questionnaire (UDQ) on deferral rates in first-time and repeat donors. We focused on the introduced question about unprotected sexual contact with a new partner. Another goal was a stratified comparison of the deferral rates of the donor questionnaire (DQ) and UDQ. METHODS: Data on donors and deferrals using the DQ and UDQ were collected at four blood establishments. The comparison included a 2-year period by questionnaire version. For the comparison of the questionnaires, an adjusted multinomial logistic regression was performed. RESULTS: The analysis included 260,848 donations. First-time (FTD) and repeat donations (RD) showed higher deferral rates with the UDQ (FTD +5.4%, RD +1.4%). Deferral due to a new partner was 3.0% in first-time and 0.4% in repeat donors. The majority of these occurred in the youngest age groups. The most frequent deferral criterion was 'disease' (5.1%). CONCLUSION: The regression revealed stronger predictors for deferral than the questionnaire version. Especially younger age carried a higher and independent risk for deferral. The additional deferrals of mainly young first-time donors due to a new sexual partner may identify those donors with potential heterosexual risk behavior who would otherwise not be identified.

Evaluation of Risk Minimisation Measures for Blood Components - Based on Reporting Rates of Transfusion-Transmitted Reactions (1997-2013).

BACKGROUND: To assess the impact of safety measures, we compared reporting rates of transfusion-related reactions before and after the implementation of six measures in 1999, 2004, 2006, 2008 and 2009. METHODS: Reporting rates of transfusion-transmitted bacterial infection (TTBI), viral infection (TTVI) and immune-mediated transfusion-related acute lung injury (TRALI) were calculated on the basis of confirmed annual reports and distributed blood components. RESULTS: The introduction of HCV NAT testing caused a significant reduction of HCV reporting rate from 1:0.6 to 1:83.16 million administered blood components (p < 0.0001), donor screening for antibodies to hepatitis B core antigen caused a reduction of HBV reporting rate from 1:2.90 to 1:10.70 million units (p = 0.0168). A significant reduction from 1:0.094 to 1:2.42 million fresh frozen plasma (FFP) units could also be achieved by risk minimisation TRALI measures (p < 0.0001). Implementation of pre-donation sampling did not result in a significant decrease in TTBI, whereas limitation of shelf life for platelet concentrate (PC) minimised the TTBI reporting rate from 1:0.088 to 1:0.19 million PC units (p = 0.041). For HIV NAT pool testing, no significant reduction in HIV transmission was found due to very low reporting rates (1:10 million versus 1:27 million blood components, p = 0.422). CONCLUSION: On the basis of haemovigilance data, a significant benefit could be demonstrated for four of six implemented safety measures.

Risk Minimization Measures for Blood Screening HIV-1 Nucleic Acid Amplification Technique Assays in Germany.

BACKGROUND: Several publications describe HIV-1 RNA false-negative results or viral load underquantitation associated with Communauté Européenne(CE)-marked qualitative or quantitative nucleic acid amplification technique (NAT) assays. 6 cases occurred during blood screening in Germany, with 2 of them causing HIV-1 transmissions to recipients of blood components. The implicated NAT assays were mono-target assays amplifying in different viral genome regions (gag or long terminal repeat). METHODS: Specimens characterized by HIV-1 NAT underquantitation or false-negative NAT results were comparatively investigated in CE-marked HIV-1 NAT systems of different design to identify potential reasons. The target regions of the viral nucleic acids were sequenced and these sequences compared to primers and probes of the assays. Potential risk minimization measures were considered for quantitative and blood-screening HIV-1 NAT systems. RESULTS: Nucleotide sequencing of the viral target region in cases of HIV-1 RNA underquantitation or false-negative test results revealed new HIV-1 variants that were mismatched with primers and probes used in some mono-target assays. So far, dualtarget NAT assays have not been associated with mismatch-based false-negative test results. From 2015, the Paul Ehrlich Institute will request HIV-1 NAT assays of dual-target design or an analogous solution for further reducing the risk in blood screening. CONCLUSION: HIV differs from other blood-borne viruses with regard to its fast evolution of new viral variants. The evolution of new sequences is hardly predictable; therefore, NAT assays with only 1 target region appear to be more vulnerable to sequence variations than dual-target assays. The associated risk may be higher for HIV-1 NAT assays used for blood screening compared to quantitative assays used for monitoring HIV-1-infected patients. In HIV-1 screening NAT assays of dual-target design may adequately address the risk imposed by new HIV-1 variants.

Blood screening nucleic acid amplification tests for human immunodeficiency virus Type 1 may require two different amplification targets.

BACKGROUND: Five cases of human immunodeficiency virus Type 1 (HIV-1) RNA-positive blood donations are described that escaped detection by three different CE-marked nucleic acid amplification technique (NAT) screening assays. These events were associated with two HIV-1 transmissions to recipients of blood components. The implicated NAT assays are monotarget assays and amplify in different viral genome regions (group-specific antigen or long terminal repeat). Investigations into the cause of the false-negative test results were initiated. STUDY DESIGN AND METHODS: Plasma specimens of the five NAT false-negative cases were comparatively investigated in 12 CE-marked HIV-1 NAT systems of differing design. The relative amplification efficiency for the HIV-1 variant was determined for each assay. Sequencing of the variants in the region targeted by each false-negative NAT assay allowed comparison with the respective primers and probes. RESULTS: Some of the NAT assays designed in a similar way to false-negative monotarget NATs also revealed deficiencies in detecting the viral variants. In each case sequencing of the assay target region in the variants demonstrated mismatches with primers and probes used by the assays. Some dual-target assays showed decreased amplification efficiency, but not false-negative results. CONCLUSION: HIV is characterized by its rapid evolution of new viral variants. The evolution of new sequences is unpredictable; NAT screening assays with a single target region appear to be more vulnerable to sequence variations than dual-target assays. Based on this experience with false-negative tests results by monotarget NAT assays, the Paul-Ehrlich-Institut is considering requesting dual-target NAT assays for HIV-1 blood donation screening in Germany.

Report on Notifications Pursuant to §21 German Transfusion Act for 2008 and 2009.

SUMMARY: This report contains the data collected in 2008 and 2009, pursuant to Section 21 German Transfusion Act as well as an overview of the supply situation during the last 10 years. In 2009, blood donation services reported a total of 7.5 million donations - the largest amount since 2000. At the same time, more than 4.7 million red blood cell (RBC) concentrates and more than 500,000 platelet concentrates were available. The number of therapeutic single plasma units decreased to 1.1 million units in 2009. The loss rate for RBC concentrates is still between 3 and 4% for the users while for the manufacturers it has decreased slightly to 1.4%. The loss rate, for platelet concentrates, on the other hand, increased in 2009, especially-what is noteworthy-for manufacturers of pooled platelet concentrates. The loss rate for apheresis platelet concentrates accounted for 5.2% compared to 17.5% for pooled platelet concentrates. As far as the users were concerned, loss rates for platelet concentrates largely remained unchanged with rates between 5 and 6%. Based on the data collected, the supply with blood components for transfusion can be regarded as assured. Nearly 2.9 million 1 of plasma for fractionation were collected in Germany in 2009. According to reports from the pharmaceutical industry, out of these, 2.6 million 1 remained on the German market, out of which only 56% were fractionated in this country. Many plasma derivatives are not manufactured in Germany, despite the large amounts of plasma collected. The supply with these products, however, is assured by imports. Overall, 16,409 autologous and 9,435 allogeneic stem cell preparations were manufactured in 2009, out of which 3,382 allogeneic preparations were exported. 3,181 autologous and 2,374 allogeneic preparations were transplanted; 187 of these products from imports. The large number of exported stem cells and the small number of imported ones suggest that no serious shortages are to be expected for the supply with these products.

Effect of Safety Measures on Bacterial Contamination Rates of Blood Components in Germany.

SUMMARY: Requirements for bacterial testing of blood components on a defined quantity as part of routine quality control were introduced in Germany by the National Advisory Committee Blood of the German Federal Ministry of Health in 1997. The philosophy was to establish standardized methods for bacterial testing. Numerous measures to reduce the risk of bacterial contamination were implemented into the blood donation and manufacturing processes between 1999 and 2002. German Blood establishments performed culture-based bacterial testing on random samples of platelet concentrates (PCs), red blood cells (RBCs) and fresh frozen plasma (FFP) and reported data out of the production periods 1998, 2001 and 2005/2006. While the bacterial contamination rate of apheresis PCs remained nearly unchanged, it decreased by 70% for pooled PCs to a rate of 0.158% in the last observation period. Leukocyte-depleted RBCs with diversion of the initial blood volume showed a contamination rate of 0.029% which is significantly lower than that of RBCs without leukocyte depletion and diversion (0.157%). The contamination rate of plasma decreased by 80%. Preventive measures resulted in a significant reduction of bacterial contamination of blood components. Long-term monitoring with standardized methods for bacteria testing supports evaluation of the cumulative effect of contamination reducing measures.

Transfusion-Transmitted Bacterial Infections - Haemovigilance Data of German Blood Establishments (1997-2010).

SUMMARY: METHODS: In order to evaluate the benefit of risk minimisation measures, reporting rates of transfusion-transmitted bacterial infections (TTBI) were calculated on the basis of annual reports and distributed blood components. Following the implementation of risk minimisation measures in 2003 and 2008, a comparison of pre- and post-implementation periods was performed. RESULTS: During a period of 14 years, 90 cases of TTBI were confirmed, 34 were caused by red blood cell (RBC) concentrates, 5 by fresh frozen plasma, and 51 by platelet concentrates (PCs). The overall reporting frequency was 1 TTBI in 1.91 million RBC units; 1 TTBI in 0.094 million PC units, and 1 TTBI-associated fatality in 0.57 million PC units. From 2001-2004 the reporting rate was 13.7 per million PC units; 2005-2008, after the implementation of pre-donation sampling; it was 10.8 per million PC units (p > 0.5). After limitation of the shelf life (2008), the reporting rate decreased to 4.49 per million PC units (p = 0.12), and one case of related fatality was reported. Agents with low pathogenicity were reported in 14 of 41 immunosuppressed patients (34%) but only in 1 of 13 patients with non-haematological/oncological diseases. CONCLUSION: TTBI and associated fatalities could be gradually reduced by the risk minimisation measures, but further strategies such as implementation of sensitive screening tests or pathogen-reducing approaches should be discussed.

Management of blood supplies during an influenza pandemic.

BACKGROUND: Blood supplies are delicate resources, particularly vulnerable to incidents affecting the health of donors. The critical impact of a pandemic on the availability of red blood cells (RBCs) has been demonstrated in previous research; however, a detailed estimate of the expected deficit is missing. This has become a priority issue in the face of the current influenza pandemic. STUDY DESIGN AND METHODS: Data from several major blood donation services were used to analyze management of blood supplies in Germany. Routine management of RBCs was extrapolated to epidemic and pandemic situations using computer simulations with a mathematical model that allows for analysis of deficits in blood supplies. RESULTS: Routine management and distribution of RBCs are driven by supply, which has marked fluctuations but does not appear to have seasonality. There seems to be a remarkable elasticity in the demand for RBCs that helps to mitigate minor crises in supply, but this is likely to be overstretched during a severe pandemic. CONCLUSION: The supply-driven management of RBCs in Germany implies that assessment of severity of shortages due to a pandemic depends on detailed knowledge about the fraction of transfusions that do not allow for postponement. Pandemic preparedness should include criteria for prioritization of transfusions.

Quality and Safety in Blood Supply in 2010.

The past two decades saw tremendous achievements in blood safety, which are due to the commitment of blood establishments and industry, progress in technology such as the improvement of serological and NAT screening tests, and stringent regulatory control. Milestones in the legislation were the inclusion of plasma derivatives in the pharmaceutical legislation of the European Community (EC) in the year 1989 and special laws for the blood sector in EC and in member states, such as the Transfusionsgesetz (Transfusion Law) in Germany. The legal frame has to be supplemented by scientific and technical guidance, which is provided on the European level by the European Directorate for the Quality of Medicines and Health Care and by the European Medicines Agency. In the member states, guidelines taking into account the national peculiarities can be elaborated, such as the German hemotherapy guidelines issued by the German Medical Association (Bundesärztekammer) in agreement with the Paul-Ehrlich-Institut. The regulatory control of screening tests, and the introduction of NAT testing lead to a remarkably high degree of safety concerning the most relevant viruses HIV, HBV and HCV. Issues needing further attention are bacterial contamination and transfusion-associated acute lung injury (TRALI). Measures aiming at minimizing risks have to be balanced against their impact on supply. In order to ensure the assured supply with safe blood products, sustained efforts and research are needed as well as a continuous dialogue among blood services, industry, physicians, patients and regulatory authorities.

Experience of mandatory nucleic acid test (NAT) screening across all blood organizations in Germany: NAT yield versus breakthrough transmissions.

BACKGROUND: Mandatory nucleic acid test (NAT) blood screening was introduced in Germany in 1999 for hepatitis C virus (HCV) RNA and in 2004 for human immunodeficiency virus Type 1 (HIV-1) RNA. Minimal sensitivity limits of 5000 IU HCV RNA/mL and 10,000 IU HIV-1 RNA/mL were defined for the individual donation facilitating testing of minipools (MPs). The NAT yield obtained from all blood organizations is summarized. Transfusion-associated virus transmissions despite NAT screening ("breakthrough transmissions") are analyzed. STUDY DESIGN AND METHODS: In Germany, a variety of NAT assays is applied for NAT screening pool sizes of up to 96 donations. Subsets of NAT yield cases were characterized with regard to viral loads by quantitative NAT and with regard to viral genotypes. Confirmed breakthrough transmissions were analyzed using different molecular and serologic assays. RESULTS: Ninety-two HCV NAT yield cases among 40.8 million and 11 HIV-1 NAT yield cases among 17.1 million donations were identified. During this period, one transmission case was confirmed for HCV and one for HIV-1. The two incidents escaped NAT detection because of low-level viremia and/or suboptimal amplification efficiency. Evidence was obtained for a case of HIV-1 nontransmission by a low-level HIV-1 contaminated red blood cell unit. CONCLUSION: NAT screening of MPs identified the vast majority of window-phase donations. A significant number of transmission cases was interdicted; breakthrough transmissions may still occur as rare events, even with individual-donation NAT in place. Sensitivity limits might be adapted to the current "state of the art" taking account of viral dynamics during early infection, incidence rates, and costs.

Evaluation of Quality Parameters for Cord Blood Donations.

SUMMARY: BACKGROUND: Umbilical cord blood (CB) is widely used for hematopoietic stem cell transplantation and holds promise for the development of innovative medicinal products. In order to find out whether the conditions for collection and storage before processing might have an impact on the quality of CB preparations, viability and the clonogenic potential were assessed. METHODS: CB was collected under field conditions. Flow cytometry was used to determine leukocytes, CD34/CD45+ cells, viability, and nucleated red blood cells (NRBC). Clonogenic activity was determined using isolated mononuclear cells (MNC). RESULTS: Neither plasma citrate concentrations nor storage temperature (within 24 h) affected cell viability or colony formation. After storage for 49-80 h, leukocyte viability declined by about 16% compared to CB stored up to 24 h. In contrast, the clonogenic activity and CD34/CD45+ cell content were not affected. A higher gestational age was associated with a lower yield of clonogenic activity compared to midterm deliveries. NRBC varied widely (median 7.3%; range 0.63-17.3%) without relation to gestational age or colony formation. There was a close correlation between the percentage of viable CD34/CD45+ cells and colony formation (r = 0.77 for CFU-GM; r = 0.75 for CFU-C). CONCLUSIONS: The content of viable CD34/CD45+ cells represents the clonogenic activity of CB preparations. Therefore, determination of viable CD34/CD45+ cells should be generally performed as a routine quality control assay.