BACKGROUND:In Japan, the risk of transfusion-transmitted hepatitis B virus (TT-HBV) infection has been reduced since 2014 by implementing individual donation nucleic acid amplification testing (ID-NAT). CASE REPORT:A male repeat blood donor in his 20s converted positive for HBV DNA and hepatitis B surface antigen. Red cell concentrate from his previous donation had been transfused into a woman in her 70s. Her serum showed HBV DNA positivity 62 days after transfusion. HBV genome sequences across two regions were shown to be identical in the donor and recipient. The HBV full-length genome sequence from the donor belonged to nonindigenous subgenotype I1. It contained double mutations A1762T and G1764A, which are associated with hepatocellular carcinoma development. The donor had no history of traveling abroad within 126 days prior to the index donation, so he was probably infected with HBV in Japan. DISCUSSION:Including this case, nine cases of TT-HBV from eight blood donations have been detected in Japan since the introduction of ID-NAT. Seven of the eight TT-HBV-related donations had HBV subgenotypes that were exotic to Japan. Exotic HBV strains spreading in Japan pose a risk of TT-HBV owing to ongoing acute HBV infection with these strains.

BACKGROUND:Hepatitis B core antibody (anti-HBc) screening has been implemented in many blood establishments to help prevent transmission of hepatitis B virus (HBV), including from donors with occult HBV infection (OBI). We review HBV screening algorithms across blood establishments globally and their potential effectiveness in reducing transmission risk. MATERIALS AND METHODS:A questionnaire on HBV screening and follow-up strategies was distributed to members of the International Society of Blood Transfusion working party on transfusion-transmitted infectious diseases. Screening data from 2022 were assimilated and analyzed. RESULTS:A total of 30 unique responses were received from 25 countries. Sixteen respondents screened all donations for anti-HBc, with 14 also screening all donations for HBV DNA. Anti-HBc prevalence was 0.42% in all blood donors and 1.19% in new donors in low-endemic countries; however, only 44% of respondents performed additional anti-HBc testing to exclude false reactivity. 0.68% of anti-HBc positive, HBsAg-negative donors had detectable HBV DNA. Ten respondents did universal HBV DNA screening without anti-HBc, whereas four respondents did not screen for either. Deferral strategies for anti-HBc positive donors were highly variable. One transfusion-transmission from an anti-HBc negative donor was reported. DISCUSSION:Anti-HBc screening identifies donors with OBI but also results in the unnecessary deferral of a significant number of donors with resolved HBV infection and donors with false-reactive anti-HBc results. Whilst confirmation of anti-HBc results could be improved to reduce donor deferral, transmission risks associated with anti-HBc negative OBI donors must be considered. In high-endemic areas, highly sensitive HBV DNA testing is required to identify infectious donors.

In Japan, 41 million blood donations have been screened for hepatitis B virus (HBV) during the past 8.4 years using individual donation nucleic acid amplification testing (ID‐NAT) and antibody to hepatitis B core antigen (anti‐HBc) screening.

BACKGROUND:More than 45 cases of transfusion-transmitted hepatitis E virus infection (TT-HEV) have been reported in Japan. Therefore, in 2020, universal individual donation nucleic acid amplification testing (ID-NAT) was implemented for HEV.STUDY DESIGN AND METHODS:We characterized HEV NAT-positive blood donors. The number of new HEV infections and the asymptomatic infection rate were estimated using the HEV NAT-positive rate. HEV RNA quantitation, phylogenetic analysis, and antibody tests were performed, and the residual risk of TT-HEV was assessed based on the lookback study results.RESULTS:A total of 5,075,100 blood donations were screened with ID-NAT during the first year of implementation, among which 2804 (0.055%; males: 0.060%, females: 0.043%) were NAT-positive with regional differences. Approximately 270,000 new HEV infection cases were estimated to occur annually in Japan, with an asymptomatic infection rate of 99.9%. The median HEV RNA concentration, excluding cases below the limit of quantification, was 205 IU/mL. Among the 1113 cases where the genotype could be determined, HEV-3 and HEV-4 accounted for 98.8% (1100) and 1.2% (13), respectively. The maximum duration of HEV viremia, including the pre- and post-ID-NAT window periods, was estimated to be 88.2 days. Within the 3 years since ID-NAT implementation, no confirmed cases of breakthrough TT-HEV were observed.DISCUSSION:Multiple indigenous HEV strains are prevalent in Japan, infecting a significant number of individuals. However, since the implementation of ID-NAT, TT-HEV has been prevented due to the test's high sensitivity.

Transfusion‐transmitted bacterial infections (TTBIs) in Japan have been largely prevented due to a short shelf life of 3.5 days after blood collection for platelet concentrate (PC) and washed PCs (WPCs; PC in which 95% plasma is replaced by platelet additive solution).

BACKGROUND:Hepatitis B virus (HBV)-positive individuals with isolated anti-HBs are found among HBV vaccine recipients and healthy blood donors with no vaccination history. HBV infectivity from blood transfusions derived from such individuals remains unclear.CASE PRESENTATION:A male patient who received transfusion with blood negative for individual donation-NAT, HBsAg and anti-HBc but weakly positive for anti-HBs developed typical transfusion-transmitted (TT)-HBV with anti-HBc response. The responsible blood donor was a frequent repeat donor showing a marked increase in anti-HBs titer without anti-HBc response 84 days after index donation. Test results for his past donations showed transient viremia with very low viral load and fluctuating low-level anti-HBs. The HBV vaccination history of this donor was unknown.DISCUSSION:Anti-HBs and anti-HBc kinetics of the donor suggest a second antibody response to new HBV challenge, representing a vaccine breakthrough case. On the other hand, transient low-level viremia and fluctuating anti-HBs in the test results of past donations suggested chronic occult HBV infection with isolated anti-HBs.CONCLUSION:Whatever the basic infection state, blood donors with isolated weak anti-HBs may include a small population with a risk of causing TT-HBV. Identifying individuals harboring such TT-HBV risk among individuals positive only for anti-HBs is difficult under current screening strategies. Active surveillance for the occurrence of TT-HBV with blood positive only for anti-HBs is necessary.

BACKGROUND:The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) essentially affects respiratory organs and tissues. SARS-CoV-2 RNAemia is often associated with more severe cases of coronavirus disease 2019 (COVID-19) compared to cases without RNAemia. To determine the impact of the pandemic on transfusion medicine, particularly transfusion-related infection, we examined the frequency of blood donation with RNAemia, the viral RNA (vRNA) concentration, and any possibility of transfusion-transmitted infection (TTI) among transfusion recipients.STUDY DESIGN AND METHODS:vRNA was examined in plasma/serum samples from 496 of 513 blood donors who reported having been infected with SARS-CoV-2 within 2 weeks of donation among a total of ca. 9.9 million blood donations in Japan between January 15, 2020, and December 31, 2021. The clinical course of patients transfused with the blood component containing vRNA was also examined.RESULTS:vRNA was detected in 23 of 496 samples. The median period from blood donation to COVID-19 onset was 1 day in 16 RNAemia-positive donors. Most samples had vRNA concentrations below the limit of quantification. Three patients were transfused with either a packed red blood cell or platelet concentrate that tested positive for vRNA, showing no COVID-19 symptoms and testing negative for vRNA in post-transfusion blood.CONCLUSION:The rate of RNAemia was 4.6% among blood donors who were found to be infected with SARS-CoV-2 shortly after donation, and vRNA concentrations in their donated blood were extremely low. There was no evidence of TTI in the recipients transfused with RNAemia-positive blood components. TTI risk in SARS-CoV-2 is negligible.

Rebecca Cardigan | Helen V. New | Lise Estcourt | Eugene Zhiburt | Rounak Dubey | Jesper Bengtsson | Magnus Jöud | Carlos Castillo | Joan Cid | Miquel Lozano | Dhana Gounder | Peter Flanagan | Sarah Morley | Gwen Clarke | Dana Devine | Salwa Hindawi | Aqeel AlOtaibi | Carolina Bonnet Bub | Jose Mauro Kutner | Toshiyuki Ikeda | Naoko Goto | Hitoshi Okazaki | Magali J. Fontaine | Jeremiah Pasion | Linda Song | Tom Latham | Jean-Louis Kerkhoffs | Masja de Haas | Jaap Jan Zwaginga | Birgit S. Gathof | Katharina Ommer | France Pirenne | Michel Raba | Anne Francois | James Daly | Tanya Powley | Nancy Dunbar

Platelet transfusions are given to prevent or treat bleeding in patients with quantitative or qualitative platelet disorders. Despite these lifesaving roles, certain complications are unavoidable even with best practices. Administration of platelet components has various risks, including allergic and anaphylactic transfusion reactions, febrile non-hemolytic transfusion reactions (FNHTRs), bacterial and viral infections, transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), transfusion-associated graft-versus-host disease (TA-GVHD) etc., some of which can be fatal. Among them, allergic and anaphylactic transfusion reactions, FNHTRs are frequent with platelet and plasma transfusions. Due to storage at room temperature, bacterial infections are more frequently caused by platelet transfusions than red blood cell or plasma transfusions. To prevent these adverse events related to platelet transfusions, various safety measures are being applied, which include well-organized donor-selection protocol, skin disinfection, sample diversion, leukoreduction, detection of bacterial contamination by culture and/or immunoassay, plasma replacement with platelet additive solution, platelet washing, and pathogen reduction technology. In contrast to other developed countries, the situation of platelet transfusions in Japan is unique in that the shelf-life of leukoreduced single-donor apheresis platelets is limited to 3 days and bacterial culture screening and pathogen reduction technologies are not implemented so far. In this article, incidence and severity of various adverse effects of platelet transfusions in Japan are described by referring to the recent data collected by two existing hemovigilance systems at the national level. Moreover, existing literatures inside and outside Japan regarding epidemiology, clinical manifestation, treatment, and mitigation strategies of adverse events associated with platelet transfusions are reviewed, which can help clinicians' appropriate use of platelet components and management of related adverse events.

Background and ObjectivesThe International Haemovigilance Network collects aggregate data on complications of blood donation from member haemovigilance systems (HVS). We analysed the data collected in 2006–2016 in order to learn from it and consider future improvements.Materials and MethodsNational HVS entered annual data on donation complications and on annual whole blood and apheresis donations in the ‘ISTARE’ (International Surveillance of Transfusion Adverse Reactions and Events) online database. We calculated national and aggregate donation complication rates.ResultsTwenty‐four HVS provided data for 138 country years (CY; median 7 CY, IQR 2–8), covering 155 M donations. The overall complication rate was 6·3/1000 donations and the median country rate 3·2/1000 (IQR 1·1–10·1). Overall and severe complication rates varied considerably between HVS. Vasovagal reactions (VVR) were most commonly reported: 4·6/1000 donations, median country rate 3·1/1000 donations (IQR 0·6–7·7). Rare complications included generalized allergic reaction (0·10/100 000) and major blood vessel injury (category available since 2015; 0·12/100 000). Eighteen HVS reported complications of whole blood donation (WBD) and apheresis separately (89 CY, 101·6 M WBD and 26·3 M apheresis donations). The median country VVR rate was 3·4/1000 WBD (IQR 1·0–9·1) and 1·5/1000 apheresis donations (1·0–4·2). Rates of venepuncture‐related complications tended to be higher for apheresis: the median country rate of reported haematomas was 0·39/1000 WBD (IQR 0·31–1·2) vs. 4·2/1000 apheresis donations (0·69–5·6).ConclusionInternational reporting allows HVS to study rates of blood donation complications and capture information about very rare events. The present variability of reporting and severity assessment hampers comparisons between HVS and requires further work.

BACKGROUNDTransfusion‐transmitted bacterial infections (TTBIs) often have serious consequences for patients. The Japanese Red Cross (JRC) has not implemented culture screening for platelet concentrate (PC), but it has maintained a shelf life of 85 hours for PC.STUDY DESIGN AND METHODSThe JRC collected reports of suspected TTBI and investigated causal relationships using PC samples and patient blood samples. PCs showing apparent abnormalities were retrieved and cultured and analyzed for bacterial growth.RESULTSThe JRC analyzed 86 samples available from 135 transfused PCs with suspected TTBIs that were collected over the past 12 years; 17 (19.8%) were culture‐positive. One, 6, and 10 TTBIs developed in patients on Days 1, 2, and 3 after PC collection, respectively. Assuming that PC is transfused on the day of issue, the TTBI risk was fourfold higher on Day 3 than on Day 2, after adjusting the TTBI incidence for the number of PCs issued per day. Compared with the model of issuing all PCs on Day 3, issuing PCs with the current distribution of storage time could have decreased the TTBI incidence by 56%. During the past 8 years, the JRC retrieved 960 PC units because of apparent abnormalities, 2.8% of which were culture‐positive.CONCLUSIONThe short shelf life of PC is associated with a low incidence of reported TTBIs, more than half of which occurred on Day 3 relative to earlier time points. Visual inspection of PC before transfusion is crucial in detecting bacterially contaminated PC despite its low positive predictive value.

: To establish preventive measures against transfusion-transmitted Hepatitis E Virus infection (TT-HEV), we ana-lyzed TT-HEV cases (n = 34) identified from 2005 to 2018, including 19 cases previously reported in Transfusion (2017; 57: 280-288). The causative blood had been donated from across Japan, with more than half donated in the Kanto-Koshinetsu area. Thirty (88.2%) blood components tested positive for HEV-RNA and negative for HEV antibodies, suggesting that most of the causative products were donated in the early stage of HEV infection. On molecular phylogenetic analysis of the 32 HEV strains of TT-HEV, 29 (90.6%) and 3 (9.4%) cases were classified as HEV-3 and HEV-4, respectively. Each was found in a different cluster, showing high genetic diversity. At least 16 (47.1%) patients were transfused under immunosuppression and developed acute hepatitis. HEV vire-mia persisted for more than 6 months in 8 immunosuppressed patients. The median maximum ALT level during the clinical course of 34 cases was 631 IU/l. The minimum infectious HEV dose through transfusion was 2.51 log IU. There was no correlation between infused dose or HEV genotype and maximum ALT value. The risk of TT-HEV has emerged in Japan. HEV RNA screening will be useful to reduce it.

BACKGROUNDDetermination of blood donor hemoglobin (Hb) levels is a pre‐requisite to ensure donor safety and blood product quality. We aimed to identify Hb measurement practices across blood donation services and to what extent differences associate with low‐Hb deferral rates.METHODSAn online survey was performed among Biomedical Excellence for Safer Transfusion (BEST) Collaborative members, extended with published data. Multivariable negative‐binomial regression models were built to estimate adjusted associations of minimum donation intervals, Hb cut‐offs (high, ≥13.5 g/dL in men or ≥ 12.5 g/dL in women, vs. lower values), iron monitoring (yes/no), providing or prescribing iron supplementation (yes/no), post‐versus pre‐donation Hb measurement and geographical location (Asian vs. rest), with low‐Hb deferral rates.RESULTSData were included from 38 blood services. Low‐Hb deferral rates varied from 0.11% to 8.81% among men and 0.84% to 31.85% among women. Services with longer minimum donation intervals had significantly lower deferral rates among both women (rate ratio, RR 0.53, 95%CI 0.33‐0.84) and men (RR 0.53, 95%CI 0.31‐0.90). In women, iron supplementation was associated with lower Hb deferral rates (RR 0.47, 95%CI 0.23‐0.94). Finally, being located in Asia was associated with higher low‐Hb deferral rates; RR 9.10 (95%CI 3.89‐21.27) for women and 6.76 (95%CI 2.45‐18.68) for men.CONCLUSIONDifferences in Hb measurement and eligibility criteria, particularly longer donation intervals and iron supplementation in women, are associated with variations in low‐Hb deferral rates. These insights could help improve both blood donation service efficiency and donor care.

はじめに 血液製剤はヒトの血液を原料としているため,その 使用によって発生する副反応をゼロにすることは不可 能である.世界の輸血副反応の安全監視体制(ヘモビ ジランス)は,国により様々なシステムを運用してい る.血液事業者の形態や輸血副反応を収集・解析す る組織も,国が直接関与する場合,赤十字社の場合, 独立した血液事業者の場合など国によって構成が異なっ ている.我が国の輸血副反応のヘモビジランスシステ ムは,医薬品医療機器法及び安全な血液製剤の安定供 給の確保等に関する法律に基づき,受血者における有 害事象は各医療施設から日本赤十字社,または重症例 に限っては直接国へ報告することとなっているが,医 療施設からの自発報告が中心のため必ずしも輸血副反 応の全容が把握されていない.副反応軽減を目指す上 で副反応の発生原因を把握しておくことは極めて重要 であり,副反応の発生原因を恒常的かつシステマティッ クに調査検討するためには,供血者の選択から受血者 の転帰まで(Blood transfusion chain)を追跡できるト レーサビリティシステムを構築することが最も有用な 解決策となる.わが国では,血液製剤の原料となる血 液の採取は,日本赤十字社が一社で行っており,transfusion chainの前半部分(供血者の選択から医療施設へ の供給)に関する情報の収集と管理は十分に確保され ている.しかし,transfusion chainの後半部分を構成す る医療施設の情報の収集と管理は,国内に 1万以上存 在する輸血を実施する各医療施設まかせで標準化され ておらず十分ではない.そこで日本輸血・細胞治療学 会では,「輸血副作用の症状項目ならびに診断項目表」 を全国的に統一された輸血副反応報告の基準として掲 示し各医療施設での利用を推奨するとともに,2007 年よりヘモビジランス委員会が中心となって「輸血製 剤副作用情報収集システム」を構築し,システム参加 医療施設が使用した全ての RBC,PC,FFP製剤の製剤 数と標準化された副反応情報を web経由で収集し,解 析結果を報告してきた. さらなる輸血の安全性の向上と適正使用の実現のた めに,我々は既存のシステムを拡充し,日本赤十字社 がもつデータと医療施設のもつデータを,データ収集・ 解析センターが血液バッグの製造番号を介して連結す

日本赤十字社では，非溶血性副作用にかかる患者検体等の調査として抗血漿タンパク抗体検査，血漿タンパク欠損検査，IgE検査，トリプターゼ検査及び抗HLA抗体検査を実施してきた．

This chapter contains sections titled: History of the Japanese Hemovigilance System Legal basis Setting up the hemovigilance system Governance of the hemovigilance system Adverse events to be reported/reporting system Concept and methodology of Japanese hemovigilance Data analysis and feedback Evaluation of hemovigilance system Look-back studies Errors and near-misses Adverse reactions Data and trends Results of data utilization for prevention and evaluation Usefulness of data from our hemovigilance system Advantages and limitations of Japanese hemovigilance system Moving towards evidence-based hemovigilance References