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Immunoadsorption as a method of antibody donation during the COVID-19 pandemic. 在 COVID-19 大流行期间将免疫吸附作为一种抗体捐赠方法。
IF 1.8 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-08-01 Epub Date: 2024-05-13 DOI: 10.1111/vox.13647
Jannik Rothenburg, Silke Rink-Baron, Lisa Müller, Philipp Niklas Ostermann, Johannes C Fischer, Derik Hermsen, Johannes Stegbauer, Anja Moldenhauer

Background and objectives: Initial therapeutic efforts to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) included the use of plasma from convalescent donors containing anti-SARS-CoV-2 antibodies. High-neutralizing antibody titres are required for therapeutic efficacy. This study aims to show that immunoadsorption followed by tangential flow filtration can be used to obtain antibody concentrates with high-neutralizing capacities.

Materials and methods: Eligible donors (n = 10, five males and three females) underwent immunoadsorption using adsorber columns specific for human antibodies. Glycine-washed out eluates of 1.5 L volume were further concentrated by tangential flow filtration using 30 kDa ultrafiltration membranes. The same membranes were applied for diafiltrations to exchange residual glycine for 0.9% normal saline.

Results: Antibody concentrates were obtained within 8 h from the start of donation and had 4.58 ± 1.95, 3.28 ± 1.28 and 2.02 ± 0.92 times higher total IgG, IgA and IgM concentrations, 3.29 ± 1.62 and 3.74 ± 0.6 times higher SARS-CoV-2 N and S antibody concentrations and 3.85 ± 1.71 times higher SARS-CoV-2 S-specific IgG concentrations compared to the donors' peripheral blood. The specific SARS-CoV-2 virus neutralization capacities increased in all but one concentrate. All antibody concentrates (50-70 mL final volume) passed microbiological tests, were free of hazardous glycine levels and could be stored at -80°C and 4°C for 1 year with 20 ± 3% antibody loss.

Conclusion: Immunoadsorption followed by tangential flow filtration is a feasible procedure to collect IgG, IgA and IgM as well as SARS-CoV-2 N- and S-specific antibody concentrates of low volume, free of albumin and coagulation factors. Whether these concentrates can be used as passive immunisation in infected patients remains to be elucidated.

背景和目的:治疗严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)的最初疗法包括使用含有抗 SARS-CoV-2 抗体的康复捐献者血浆。治疗效果需要高中和性抗体滴度。本研究旨在证明免疫吸附后切向流过滤可用于获得具有高中和作用的抗体浓缩物:符合条件的供体(n = 10,5 男 3 女)使用人类抗体特异性吸附柱进行免疫吸附。用 30 kDa 超滤膜进行切向流过滤,进一步浓缩甘氨酸洗脱液(1.5 升)。用同样的膜进行重过滤,将残留的甘氨酸换成 0.9% 的生理盐水:与捐献者外周血相比,抗体浓缩物的总 IgG、IgA 和 IgM 浓度分别为 4.58 ± 1.95、3.28 ± 1.28 和 2.02 ± 0.92 倍,SARS-CoV-2 N 和 S 抗体浓度分别为 3.29 ± 1.62 和 3.74 ± 0.6 倍,SARS-CoV-2 S 特异性 IgG 浓度为 3.85 ± 1.71 倍。除一种浓缩液外,其他所有浓缩液的 SARS-CoV-2 病毒特异性中和能力都有所提高。所有抗体浓缩液(50-70 毫升最终体积)都通过了微生物测试,不含有害的甘氨酸,可在 -80°C 和 4°C 下保存 1 年,抗体损失率为 20 ± 3%:结论:免疫吸附后切向流过滤是收集 IgG、IgA 和 IgM 以及 SARS-CoV-2 N 和 S 特异性抗体浓缩物的可行方法,浓缩物体积小,不含白蛋白和凝血因子。这些浓缩物是否可用于感染患者的被动免疫,还有待进一步阐明。
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引用次数: 0
Criteria for storage of cord blood units at Japan's largest cord blood bank. 日本最大脐带血库的脐带血储存标准。
IF 1.8 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-08-01 Epub Date: 2024-06-05 DOI: 10.1111/vox.13687
Naoko Watanabe-Okochi, Takeshi Odajima, Miyuki Ito, Naoya Yamada, Manami Shinozaki, Mutsuko Minemoto, Fumihiko Ishimaru, Kazuo Muroi, Minoko Takanashi

Background and objectives: In Japan, cord blood transplantations exceed those done with adult-sourced unrelated stem cells. This study analyses cord blood (CB) storage criteria to maintain high-quality CB units.

Materials and methods: The Kanto-Koshinetsu Cord Blood Bank received 29,795 units from 2014 to 2021, mostly >60 mL, and 5486 (18.4%) were stored as transplantable units. We investigated the mother's gestational period, CB volume, total nucleated cells (TNCs), CD34+ cells, total colony-forming units (CFUs), time from collection to reception and cryopreservation, cell viability, and the reasons for not storing a unit.

Results: The average time from collection to reception of 29,795 units was 18.0 h. The most common reason for not storing a CB unit was low cell numbers (pre-processing TNC count <1.2 billion), accounting for 67.9% of the units received. There was no correlation between the CB volume and the CD34+ cell count. The shorter the gestational period, the lower the TNC count, but the higher the CD34+ cell count. There was no correlation between the time from collection to cryopreservation, within a 36-h time limit, and the CD34+ cell recovery rate.

Conclusion: We could accept units with a TNC count <1.2 billion and a CB volume <60 mL from a gestational period of 38 weeks or less if we did a pre-processing CD34+ cell count. This would secure more units rich in CD34+ cells.

背景和目的:在日本,脐带血移植超过了使用成人来源的非亲属干细胞进行的移植。本研究分析了脐带血(CB)储存标准,以保持高质量的 CB 单位:关东甲信越脐带血库从 2014 年至 2021 年共接收了 29,795 份脐带血,其中大部分大于 60 毫升,5486 份(18.4%)作为可移植脐带血储存。我们调查了母亲的妊娠期、脐带血容量、有核细胞总数(TNC)、CD34+细胞、集落形成单位总数(CFU)、从采集到接收和冷冻保存的时间、细胞存活率以及未储存单位的原因:从采集到接收 29,795 个细胞单位的平均时间为 18.0 小时。不储存 CB 细胞单位的最常见原因是细胞数量少(处理前 TNC 计数 结论):我们可以接收 TNC 细胞数
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引用次数: 0
Treatment of Acute Bleeding Episodes with rFVIIa 用 rFVIIa 治疗急性出血发作
IF 2.7 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-07-13 DOI: 10.1111/j.1423-0410.1999.tb00013.x
J. Ingerslev, O. Sneppen, I. Hvid, U. Fredberg, H.L. Kristensen, S. Sindet‐Petersen
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引用次数: 0
Epitope Specificity and Inactivation Mechanisms of Factor VIII Inhibitor Antibodies 因子 VIII 抑制剂抗体的表位特异性和失活机制
IF 2.7 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-07-13 DOI: 10.1111/j.1423-0410.1999.tb00006.x
Dorothea Scandella
The domain specificity of anti‐factor VIII (FVIII) inhibitor antibodies was determined in assays using FVIII domains generated by thrombin cleavage or expressed as recombinant polypeptides to neutralise the inhibitor. The results revealed the existence of three major types of inhibitors, and various combinations of these antibodies were found in haemophilic and autoantibody patients. Anti‐A2 domain inhibitors prevent normal function of the FVIII/factor IXa (FIXa)/phospholipid complex in an unknown manner. Binding of FVIII to phospholipid and to von Willebrand factor is blocked by anti‐C2 domain antibodies, and the binding of FVIII to FIXa is prevented by anti‐A3 domain antibodies. A rare type of inhibitor prevents release of activated FVIII from von Willebrand factor (vWf), and another probably interferes with FVIII binding to factor X (FX) because it shares the epitope of a monoclonal antibody with this property.
在使用凝血酶裂解产生的或表达为重组多肽的 FVIII 结构域来中和抑制剂的试验中,确定了抗因子 VIII(FVIII)抑制剂抗体的结构域特异性。结果显示存在三种主要类型的抑制剂,在血友病患者和自身抗体患者中发现了这些抗体的各种组合。抗A2结构域抑制剂以一种未知的方式阻止FVIII/因子IXa(FIXa)/磷脂复合物的正常功能。抗C2结构域抗体会阻止FVIII与磷脂和von Willebrand因子结合,抗A3结构域抗体会阻止FVIII与FIXa结合。一种罕见的抑制剂可阻止活化的 FVIII 从 von Willebrand 因子(vWf)中释放,另一种抑制剂可能会干扰 FVIII 与 X 因子(FX)的结合,因为它与具有这种特性的单克隆抗体的表位相同。
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引用次数: 0
Induction of Immune Tolerance in Haemophilia A Inhibitor Patients by the ‘Bonn Protocol‘: Predictive Parameter for Therapy Duration and Outcome 通过 "波恩方案 "诱导血友病 A 抑制剂患者的免疫耐受:治疗时间和治疗结果的预测参数
IF 2.7 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-07-13 DOI: 10.1111/j.1423-0410.1999.tb00015.x
J. Oldenburg, R. Schwaab, H.H. Brackmann
The treatment of inhibitors is one of the most challenging fields in haemophilia care. The present study reports the results of 60 haemophilia A inhibitor patients treated according to the ‘Bonn Protocol’ and evaluates predictors for the duration and outcome of therapy. Successful immune tolerance could be achieved in 52 patients (86.7%) while the therapy failed in eight patients (13.3%). The immune tolerance achieved was longlasting in all 52 patients, with no inhibitor relapse in up to 20‐years follow‐up. The course of ITT was influenced by several factors. Interruptions of treatment during the ITT course led to a substantial prolongation of ITT duration (median 39.9 months vs 14.1 months in continuously treated patients). Infections of intravenous central lines appeared to be frequently coincided with ITT prolongation and sometimes even ITT failure. Further negative predictors towards the ITT duration were high inhibitor titres at enrolment or during ITT. There was also a tendency towards longer ITT duration in patients exhibiting the prevalent intron 22 inversion. As a consequence of our data treatment interruptions and infections of intravenous central lines should be avoided during the course of ITT. Furthermore our data suggest, that ITT should be started at low inhibitor titres preferably with a high factor VIII dosage protocol.
抑制剂的治疗是血友病治疗中最具挑战性的领域之一。本研究报告了根据 "波恩方案 "对 60 名血友病 A 抑制剂患者进行治疗的结果,并对治疗持续时间和结果的预测因素进行了评估。52名患者(86.7%)成功获得了免疫耐受,8名患者(13.3%)治疗失败。所有 52 名患者都获得了持久的免疫耐受,在长达 20 年的随访中没有抑制剂复发。ITT 的疗程受多种因素影响。在 ITT 疗程中中断治疗导致 ITT 持续时间大幅延长(中位数为 39.9 个月,连续治疗患者为 14.1 个月)。静脉中心管感染似乎经常与 ITT 延长同时发生,有时甚至与 ITT 失败同时发生。入组或 ITT 期间抑制剂滴度高也是 ITT 持续时间的负面预测因素。此外,内含子 22 倒置现象普遍的患者的 ITT 持续时间也有延长的趋势。根据我们的数据,在 ITT 期间应避免治疗中断和静脉中心管路感染。此外,我们的数据还表明,ITT 应在抑制剂滴度较低时开始,最好采用高 VIII 因子剂量方案。
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引用次数: 0
Epidemiology of Inhibitor Development in Haemophilia A Patients Treated with Virus‐Inactivated Plasma‐Derived Clotting Factor Concentrates 使用病毒灭活血浆凝血因子浓缩物治疗的 A 型血友病患者出现抑制剂的流行病学特征
IF 2.7 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-07-13 DOI: 10.1111/j.1423-0410.1999.tb00002.x
Wolfhart Kreuz, Carmen Escuriola‐Ettingshausen, Inmaculada Martinez‐Saguer, Monika Kaiml, Bernhard Kornhuber
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引用次数: 0
Human Factor VIII for Bleeding in Patients with Inhibitors 用于抑制剂患者出血的人类因子 VIII
IF 2.7 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-07-13 DOI: 10.1111/j.1423-0410.1999.tb00014.x
Carol K. Kasper
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引用次数: 0
Factor Xa and Prothrombin: Mechanism of Action of FEIBA 因子 Xa 和凝血酶原:FEIBA 的作用机制
IF 2.7 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-07-13 DOI: 10.1111/j.1423-0410.1999.tb00020.x
Peter L. Turecek, Katalin Varadi, Herbert Gritsch, Wilfried Auer, Ludwig Pichler, Gerald Eder, Hans Peter Schwarz
A complex consisting of activated factor X (FX) (enzyme) and prothrombin (substrate), both highly purified from human plasma and virus inactivated, was formulated, characterised biochemically as well as in animal studies, and given the name Partial Prothrombinase (PPT). In vitro, PPT shortened the clotting time of a high‐titre human factor VIII (FVIII) inhibitor plasma in a manner similar to that of the activated prothrombin complex concentrate FEIBA and triggered coagulation in plasma samples in which factor V (FV) is present. In vivo, the ability of PPT to activate coagulation in both chimpanzees and baboons was equivalent to that of FEIBA. PPT also triggered coagulation in a von Willebrand factor(vWF)‐deficient dog and controlled bleeding in rabbits with antibody‐induced haemophilia A. Thus, studying the mechanism of action of PPT also explains the therapeutic principle of FEIBA.
一种由活化的 X 因子(FX)(酶)和凝血酶原(底物)组成的复合物被配制出来,这两种复合物都是从人血浆中高度纯化并经病毒灭活的,并在生物化学和动物实验中进行了表征,被命名为部分凝血酶原酶(PPT)。在体外,PPT 能缩短高滴度人类因子 VIII(FVIII)抑制剂血浆的凝血时间,其方式与活化凝血酶原复合物浓缩物 FEIBA 相似,并能触发存在因子 V(FV)的血浆样本的凝血。在黑猩猩和狒狒体内,PPT 激活凝血的能力与 FEIBA 相当。此外,PPT 还能触发缺乏 von Willebrand 因子(vWF)的狗体内的凝血过程,并控制抗体诱发的 A 型血友病兔子的出血。
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引用次数: 0
Measuring of Factor VIII Inhibitors according to the Bethesda Method in Patients with Product‐Related Inhibitors in Comparison to Non‐Product Related Inhibitors 根据贝塞斯达法测量产品相关抑制剂与非产品相关抑制剂患者体内的因子 VIII 抑制剂比较
IF 2.7 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-07-13 DOI: 10.1111/j.1423-0410.1999.tb00022.x
U. Budde, E. Drewke
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引用次数: 0
The German National Immune Tolerance Registry, 1997 Update 德国国家免疫耐受登记处,1997 年最新情况
IF 2.7 4区 医学 Q3 HEMATOLOGY Pub Date : 2024-07-13 DOI: 10.1111/j.1423-0410.1999.tb00009.x
H. Lenk, Study Group of German Haemophilia Centres
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引用次数: 0
期刊
Vox Sanguinis
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