Transfusion Medicine and Hemotherapy最新文献

Background: In general, the detection of the causative drug in patients who develop allergies related to drugs is very complicated or even impossible. To date, urine and serum samples from patients who have received the drug suspected to be associated with adverse drug reactions (ex vivo antigens) have rarely been used to detect metabolite-dependent antibodies (mdab) to red blood cells (RBCs). Here, we investigated whether ex vivo drug metabolism using primary human hepatocytes might be a better alternative for obtaining the metabolites needed for the assays.

Methods: Two serum samples containing mdab from 2 patients who had previously developed severe immune hemolytic anemia associated with diclofenac and 5-FU, respectively, were retested in the presence of urinary metabolites from patients and from ex vivo metabolism in primary human hepatocytes seeded in 2D monoculture.

Results: Both mdab tested were detectable with urine as a source of drug metabolites, and with ex vivo drug metabolites obtained from the hepatocyte cell culture, using enzyme-treated RBCs.

Conclusion: The results obtained in this study are encouraging, not only in terms of improving the detection of mdab to blood cells but also in other forms of allergies related to drugs. Ex vivo drug metabolism using hepatocyte cell culture may represent a standardized and controllable alternative to urine or serum samples for the detection of mdab to any affected human cells.

Background: Maternal alloimmunization can lead to significant perinatal morbidity and mortality. The rate of maternal alloimmunization reported is varied across the studies conducted in India. A systematic review will help in understanding the overall prevalence of alloimmunization. Additionally, the study aimed at understanding the factors affecting the rate of maternal alloimmunization.

Methods: A search of original articles reporting rate of alloimmunization among antenatal women published in English language from India was performed in Scopus, Google Scholar, MEDLINE, and CINAHL databases. Two independent teams, each comprising two reviewers, extracted data from the eligible studies. Meta-analysis was performed for cumulative estimates by binary random-effects model using the restricted maximum likelihood method.

Results: Fourteen studies published between 2011 and 2023 were included. The pooled prevalence of maternal alloimmunization was 2.0 per 100 (95% CI: 1.5-2.5) among antenatal women, with significant heterogeneity across studies. Anti-D was the most frequently identified antibody (56.39%), followed by anti-D + anti-C (10.68%) and anti-E (5.71%). Higher risk of alloimmunization was observed in women with Rhesus D-negative blood group, multigravida status, history of blood transfusion, and bad obstetric history.

Conclusion: Despite the availability of anti-D prophylaxis, over half of the alloimmunized women had anti-D antibodies, indicating potential gaps in prevention strategies. Further research is needed to understand these gaps and implement effective interventions to minimize this preventable cause of fetal and neonatal complications. For girls and women of reproductive age, providing prohylactic antigen-matched (Rh and Kell) red cell units when transfusion is needed may reduce the burden of red cell alloimmunization.

Background: Antibodies of the mother, which are directed against paternal antigens on platelets of the child, can lead to the destruction of the fetal blood cells in the circulation after diaplacental passage. The clinical picture of fetal-neonatal alloimmune thrombocytopenia (FNAIT) is characterized by bleeding, of which intracranial bleeding is particularly feared. Our understanding of the pathophysiology of FNAIT and its targeted prophylaxis and therapy has improved significantly in recent years.

Summary: FNAIT by anti-HPA-1a is the best studied. How exactly the mother is immunized is not known for certain, but, in clinically apparent cases, immunization usually occurs in the first pregnancy of an HLA-DRB3*01:01-positive, HPA-1a-negative woman. There is no convincing basis for assigning immunization against HPA-5b and against HLA class I any significance in the development of fetal thrombocytopenia. Newborns of mothers with anti-HPA-1a present a broad clinical picture ranging from isolated, clinically unremarkable thrombocytopenia to intracranial hemorrhage (ICH; in approx. 1-10% of cases). ICH usually occurs intrauterine (before week 28). There are indications that, in addition to the fetal platelets, the placenta can also be affected by anti-HPA-1a. As there are no screening programmes, the index diagnosis of FNAIT is random. It is made by serological and genetic laboratory tests. Predicting outcome in a subsequent pregnancy is problematic if the child is antigen-positive.

Key messages: With a first-born child with severe thrombocytopenia, the probability of a recurrence of severe thrombocytopenia is around 70%. Without ICH, the probability of ICH in the subsequent pregnancy is low but not zero, and with ICH the recurrence rate is high. There is no established laboratory diagnostic method to predict the severity of thrombocytopenia or the occurrence of ICH. Prophylaxis with immunoglobulins (IVIgs) is considered effective. Pharmaceutics that block placental transport are currently undergoing clinical trials and may replace IVIgs in the future. Intrauterine platelet transfusions should no longer be performed. For the mature, thrombocytopenic newborn without internal hemorrhage, a platelet transfusion is advisable for platelet counts <25 g/L.

Introduction: Timely and accurate referral of pregnancies with red blood cell alloantibodies is essential to prevent perinatal death or long-term adverse consequences in hemolytic disease of the fetus and newborn (HDFN). Classically, antibody titers are used to select high-risk pregnancies. Research suggested that also IgG-Fc fucosylation could be an important pathological feature. We evaluated the diagnostic potential of IgG-Fc fucosylation in identifying high-risk pregnancies, and we report on a flowcytometric assay that integrates antibody quantity, antibody subclass and fetal FcγRIIIa affinity.

Methods: Maternal serum samples from a nationwide prospective cohort of D-alloimmunized pregnancies, between 2014 and 2017, were used to evaluate IgG-Fc glycosylation in mass spectrometry (n = 64) and the flowcytometric assay (n = 90). Results were compared to standard-of-care titers and antibody-dependent cellular cytotoxicity (ADCC) assay results. Receiver operating characteristic (ROC) curves were used to assess and quantify predictive values.

Results: The cohort for mass-spectrometry analysis consisted of 31 pregnancies without transfusions (48%), 16 with intrauterine transfusion (IUT) (25%), and 17 (27%) with postnatal transfusions only. The flowcytometric assay consisted of 53 (59%) pregnancies without transfusions, 17 (19%) pregnancies with IUT, and 20 (22%) pregnancies with postnatal transfusions only, suggesting that severe HDFN was overrepresented. Anti-D IgG1 and IgG3-Fc-fucosylation levels were lower in groups requiring transfusions, but no distinct difference between groups was detected. No significant difference in other glycan traits was found. Among sera from 90 D-alloimmunized pregnancies evaluated in the flowcytometric assay, we found significant differences in IgG and FcγRIIIa bindings between pregnancies without transfusions and with IUT, suggesting a potential predictive value for the need for IUTs. ROC analyses revealed a lower false-positive rate at a 100% sensitivity in the prediction of pregnancies at risk for fetal anemia through the flowcytometric assay (20.8% for IgG binding and 43.1% for FcγRIIIa binding) compared to the titer and ADCC (74.6%).

Conclusion: Anti-D IgG-Fc-fucosylation levels tended to be lower in pregnancies with IUT but could not distinguish pregnancies with or without IUT in this cohort. The flowcytometric assay, measuring IgG levels and functional FcγRIIIa binding, indicates that the specificity of serological monitoring in HDFN may be improved. Considering an overrepresentation of severe HDFN in this cohort, we advise to confirm these findings in a prospective cohort within a routine setting.

Background and objectives: Feto-maternal incompatibilities such as rhesus (Rh) (D) alloimmunization remain a critical cause of neonatal morbidity despite advances in prevention. While anti-D prophylaxis has significantly reduced hemolytic disease of the fetus and newborn, confusion, emotional distress, and misinformation persist. This study aimed to explore how parents interpret and respond to Rh incompatibility through web-based discussions, highlighting concerns, misconceptions, and informational needs.

Methods: A qualitative, inductive thematic analysis was conducted on 312 publicly available posts from Reddit, Facebook groups, YouTube comments, and parenting forums (2018-2024). Posts were retrieved using systematic keyword searches and included if they addressed Rh incompatibility, anti-D prophylaxis, or related interventions. Two researchers independently coded the data using NVivo, and themes were developed iteratively.

Results: Six major themes emerged: (1) risk perceptions (uncertainty about fetal harm), (2) emotional burden (anxiety, guilt, confusion), (3) understanding anti-D (misconceptions about timing and purpose), (4) treatment confusion (misunderstanding phototherapy and transfusions), (5) doctor-patient trust gaps, and (6) community misinformation (conspiracy theories and anecdotal remedies). Many users reported inadequate explanations from providers and turned to online forums for clarity - often encountering conflicting or incorrect information.

Conclusion: Web-based narratives map parental anxieties and highlight the need for improved digital health communication. Clinicians and health systems should develop culturally sensitive, web-compatible educational strategies to guide expectant parents toward reliable information and reduce misinformation-driven risk. Cultural references, especially from Turkish-language forums, should be interpreted cautiously in light of contextual and linguistic nuances.

Introduction: B₃ is known to be one of the B subtypes that are characterized by serologic mixed-field agglutination. The proportion of Chinese Han individuals with the B₃ subtype (B type) and AB₃ subtype (AB type) is about 1/900 and 1/1,800, respectively. Here, we identified a novel ABO subgroup allele that caused B₃ phenotype.

Methods: The ABO phenotypes of the proband and his father were typed with the traditional test tube method. The ABO genotype was analyzed by SMRT sequencing.

Results: A c.122delG variant was identified in both the proband and his father, who exhibited the B₃ phenotype. This variation results in a premature stop codon, leading to mixed-field agglutination of the serological B antigen.

Conclusion: The novel variation of c.122delG in the exon 3 of ABO*B3.0x allele were identified in Chinese individuals, resulting in mixed-field agglutination of B antigen expression and the formation of ABO subtypes.

Background: Platelet transfusion is essential for preventing and treating hemorrhage in oncology patients and can markedly improve quality of life and survival. However, access to platelet concentrates is often limited by global shortages and logistical constraints, especially in low-resource settings.

Summary: Maintaining product quality requires stringent donor screening, pathogen-reduction technologies, and optimized storage conditions to preserve hemostatic function and reduce adverse reactions. Common transfusion-related complications (e.g., alloimmunization, non-hemolytic reactions, and circulatory overload) underscore the importance of real-time monitoring and individualized transfusion protocols. Emerging thrombopoietin receptor agonists, such as romiplostim and eltrombopag, exhibited benefit in reducing transfusion dependency and merit further study in cancer-associated thrombocytopenia. This review aims to summarize the research advances and clinical guidelines on platelet transfusion, including platelet production methods, transfusion dosage, pathogen inactivation, leucocyte depletion, types of cancer-related thrombocytopenias, and platelet transfusion strategies and to discuss future research directions and perspectives.

Key messages: While platelet transfusions remain indispensable for mitigating bleeding risk in immunotherapy and CAR-T recipients, the heterogeneity of patient responses underscores the need for prospective trials to evaluate the impact of transfusion practices on both hemostatic and immunologic outcomes.

Introduction: Among pathogen inactivation methods for blood products, an ultraviolet C (UVC) irradiation has been attracting attention. We previously reported that 265 nm UV-LED (UVC-LED) effectively prevents bacterial infection. However, the effect of UVC-LED on plasma was not considered. This study aimed to explore the effects of high-dose UVC-LED irradiation, required for viral inactivation, on plasma hemostatic potential.

Methods: After irradiation of plasma with high-dose UVC-LED for 60 min, the activities of coagulation factors and coagulation inhibitors and von Willebrand factor (VWF) antigen levels were determined. VWF multimer assay and global hemostatic analysis using reconstituted blood under flow were also conducted.

Results: UVC-LED irradiation prolonged PT and activated partial thromboplastin time in a fluence-dependent manner. Fibrinogen levels and factors V and XI activities decreased to 40-47% of pre-irradiation levels. VWF multimer analysis revealed a striking reduction in high-molecular-weight VWF multimers, irrespective to ADAMTS13 activity, while VWF antigen levels showed a slight decrease. Electrophoresis under reducing conditions indicated minimal changes in the 250 kDa-VWF subunit band, suggesting that UVC-LED irradiation disrupts inter-subunit disulfide bonds in VWF multimers. Global hemostatic analysis using reconstituted blood with irradiated plasma showed a marked prolongation in primary hemostasis, indicating impaired platelet adhesion to collagen, reflecting reduced high-molecular-weight VWF multimers.

Conclusions: We demonstrated for the first time that a high-dose UVC irradiation to plasma cleaves the inter-subunit disulfide bonds of VWF multimers and reduces the molecular size. In plasma products, the balance between maintaining hemostatic activity and inactivating various pathogens by UVC irradiation is a challenge for the future.

[This corrects the article DOI: 10.1159/000502158.].

Background and objectives: Blood donor release prior to donation by a physician is mandatory in Germany according to current guidelines. Due to shortage of qualified staff, the German Transfusion Act was modified allowing the use of telemedicine. The aim of the present study was to investigate the feasibility of remote plasma donor release with respect to donor acceptance and safety.

Study design and methods: In September and October 2024, remote donor release was studied in two plasmapheresis centres. Physicians not present in the participating centres digitally evaluated donor eligibility and released donors for plasma donation. Donors were asked about the procedure by means of a questionnaire after donation. Additionally, staff had the possibility to rate the procedure at the end of the study. Donor adverse events (AEs) were recorded and their severity and causality related to plasmapheresis were rated.

Results: A total of 243 donors fulfilled the inclusion criteria and were included in the study. Rating of donation safety by donors as well as future use of telemedicine procedures was fine. Staff also welcomed the introduction of telemedicine. The possible time saving of waiting time due to the use of telemedicine was appreciated. One mild AE was reported and the rate of AEs was 0.41%.

Conclusion: Our pilot study shows that remote release of plasma donors is feasible and accepted by both donors and staff. There were no concerns about donation safety.