Blood Transfusion

Cryoprecipitate should not be the essential medicine recommended by the WHO to treat haemophilia

Mike Makris, Cedric Hermans — Tue, 21 Jan 2025 00:00:00 +0000

This letter to the editor challenges the inclusion of cryoprecipitate on the WHO list of essential medicines to treat haemophilia.

Recommending defunct therapies is a safety risk for hemophilia

Glenn Pierce, Brian O'Mahony, Radoslaw Kaczmarek, Salome Mekhuzia, Mark Skinner — Tue, 21 Jan 2025 00:00:00 +0000

We believe the article promoting the use of pathogen-reduced cryoprecipitate and untreated cryoprecipitate takes hemophilia care back 60 years, to a time before clotting factor concentrates (CFCs), extended half life CFCs, and Factor VIII mimetic bispecific antibodies were available. All of these classes are used prophylactically to prevent bleeding, whereas cryo is only used reactively, to treat bleeding. On-demand therapy of bleeding results in morbidity in nearly all patients and mortality in some, whereas prophylaxis can prevent or delay bleeding sequelae depending on the class of treatment used. In addition, since pathogen-reduced cryo is only available in 3 countries (including the USA which does not use it for hemophilia), untreated cryoprecipitate may be used and will cause some HIV and hepatitis infections in endemic countries with prolonged use, an unacceptable risk in 2024.

Response to comments on inclusion of cryoprecipitate, pathogen-reduced on the WHO model lists of essential medicines for adults and children: a call for action

Tue, 21 Jan 2025 00:00:00 +0000

Noninvasive fetal blood group antigen genotyping

Frederik Banch Clausen, C Ellen van der Schoot — Mon, 29 Jan 2024 00:00:00 +0000

Noninvasive fetal blood group antigen genotyping serves as a diagnostic tool to predict the risk of hemolytic disease of the fetus and newborn in pregnancies of immunized women. In addition, fetal RHD genotyping is used as an antenatal screening to guide targeted use of immunoglobulin prophylaxis in non-immunized RhD negative, pregnant women. Based on testing of cell-free DNA extracted from maternal plasma, these noninvasive assays demonstrate high performance accuracies. Consequently, noninvasive fetal blood group antigen genotyping has become standard care in transfusion medicine.

Comprehensive analysis of parvovirus B19 infection in blood donors: epidemiological trend and implications for transfusion safety and management strategies in Italy

Mon, 16 Dec 2024 00:00:00 +0000

Parvovirus B19 (B19V) presents a significant concern in the context of blood transfusion safety, given its potential for transmission through contaminated blood products, and the increased viral circulation recently reported across Europe. This study examines the recent epidemiological trends of B19V in Italy, where a notable increase in B19V-positive plasma units was observed during early 2024. While routine NAT testing for B19V in individual blood donations is not currently justified, the existing screening protocols for plasma intended for industrial fractionation are crucial to ensure the safety of plasma-derived medicinal products. However, this situation requires careful consideration of the optimal management of viremic donors and the implementation of targeted look back procedures to trace and monitor recipients of labile blood components. To address these issues, we propose an algorithm for managing both donors and recipients in cases of B19V positivity. These measures aim to balance recipient safety with minimising donor loss, while also addressing significant operational and ethical considerations within blood establishments.

In memoriam of Pietro Bonomo

Giuseppe Aprili — Thu, 19 Dec 2024 00:00:00 +0000

PREVIEW

Just a few, heartfelt words written with an attempt to match the sobriety, elegance and kindness of a man who, without ever raising his voice and disliking self-congratulation and arrogance, left his mark on our lives as men and professionals.
A man of science and vocation, protagonist of 50 years of transfusion history that he was able to interpret and contribute to, facilitating progress along that fascinating path in which a tumultuous succession of scientific discoveries, technological innovations, and organizational changes marked the establishment of a scientific discipline - Transfusion Medicine - which, thanks precisely to these formidable, innovative driving forces, has acquired a key role in healthcare organizations and in the development of many branches of medical and surgical sciences. [ ... ]

Revision and update of the position paper on the management of notifications of donors with Creutzfeldt-Jakob disease in Italy

Vito Vetrugno, Anna Ladogana, Vincenzo De Angelis — Tue, 17 Sep 2024 00:00:00 +0000

Notifications of blood and plasma donors who have developed Creutzfeldt-Jakob disease (CJD), and whose donations, collected in the pre-clinical phase of the disease, have entered industrial pools for the production of plasma-derived medicinal products (PDMPs), have highlighted the need to develop a technical-scientific document (position paper). This document outlines the prevention, management and communication measures to be adopted in such cases, and will be shared among the institutions involved: Italian Medicine Agency (AIFA), National Blood Center (CNS), Istituto Superiore di Sanità (ISS) and Ministry of Health. The first position paper on this matter titled“MANAGEMENT OF NOTIFICATIONS OF DONORS WITH CREUTZFELDT-JAKOB DISEASE (POST DONATION INFORMATION)”, was initially adopted by AIFA in December 2012 and then published in 2014¹. Current revision (ten years later) of the former Position Paper is to update available scientific evidence, and so, redefine the procedures to be followed to manage a possible precautionary quarantine (ban of use) or a possible recall of PDMPs. In particular, the document aims to define, the procedures to be followed to manage a possible precautionary ban on use or a possible withdrawal of PDMPs based on the most recent scientific evidence and international guidelines/recommendations. The goal is to minimize the potential shortage of life-saving PDMPs. Additionally, it will outline the methods and contents of the risk communication to professionals, patients, and public opinion.

Rh disease in Mexico: evaluating regional and institutional differences in treatment availability and disease management

Thu, 08 Aug 2024 00:00:00 +0000

Background - Rh disease occurs following maternal alloimmunization, which can develop due to RhD blood group antigen incompatibility between a mother and her fetus. Despite developing robust clinical protocols for effective immunoprophylaxis over the last 50+ years, a significant global burden of Rh disease still exists, particularly in low/middle-income countries such as Mexico.

Materials and methods - This study examined disparities in the allocation of maternal and child health resources, as well as clinical knowledge regarding Rh disease, to gain insight into why Rh disease remains prevalent in Mexico. To this end, an 11-question survey was sent to members of the Federación Mexicana de Colegios de Obstetricia y Ginecología (FEMECOG) to evaluate their knowledge of the availability and implementation of anti-RhD immunoglobulin prophylaxis in their practices and institutions, and about managing Rh disease by monitoring fetal anemia risk and providing intrauterine treatment when necessary. Responses were separated by region, and chi-square two-by-two contingency tests were performed to evaluate regional and institutional differences.

Results - Significant variations in prevention and treatment were found within the Mexican healthcare system, particularly, with regard to providing anti-RhD immunoglobulin to prevent alloimmunization, which is critically important for preventing Rh disease. Specifically, Regions 5, 6, and 7 were most lacking in this regard.

Discussion - This study highlights differences in the Mexican healthcare system in preventing and treating Rh disease. Closing the gap in the availability of
anti-RhD immunoglobulin should take priority in future efforts aimed at providing equitable care, because this will lead to the more preferable outcome of preventing Rh disease, rather than forcing patients to seek out more complex measures for treating Rh disease after it develops. These data can be used to create strategies to understand and eliminate these healthcare disparities.

How do we transfuse children in Italy? Results of a national survey

Fri, 29 Nov 2024 00:00:00 +0000

Background - Adherence to optimal practices in the preparation and issuance of pediatric blood components can significantly influence patient care outcomes. This study aims to examine the blood banking procedures across prominent Italian children’s hospitals, with the goal of identifying both consistent and potentially divergent standards within this field.

Materials and methods - A survey was conducted among the blood banks affiliated with the Italian Association of Pediatric Hospitals. Modeled after the AABB Neonatal and Pediatric Blood Bank Practices Survey, the questionnaire comprised 25 questions covering hospital characteristics, definitions of the neonatal period, pre-transfusion tests, blood component availability, and irradiation protocols.

Results - Fourteen out of the sixteen invited blood banks participated in the survey. The findings revealed a wide range of practices among the surveyed hospitals. Major differences were noted in the neonatal period definition, pre-transfusion compatibility procedures, and platelet transfusion protocols. All hospitals provided leukodepleted packed red blood cells (pRBCs), with differences in availability of autologous blood and reconstituted whole blood. Irradiated blood components were universally accessible, with differences in post-irradiation acceptable storage time. Additionally, differences in dosages for packed red blood cells (pRBCs) and platelet concentrates (PCs) were observed across hospitals.

Conclusions - Standardized guidelines for pediatric transfusion practices within Italian blood banks are of paramount importance. The observed variability underscores the necessity for sharing best practices among centers supplying blood components to pediatric patients.

Red blood cell transfusion in patients undergoing elective primary glioblastoma resection

Thu, 11 Jan 2024 00:00:00 +0000

Background - Red blood cell (RBC) transfusion in patients undergoing major elective cranial surgery is associated with increased postoperative morbidity and mortality. This study aims to identify the clinical outcome of transfused glioblastoma patients undergoing primary surgical tumor resection and identify risk factors for RBC transfusion.

Material and methods - Between 2009 and 2019, 406 patients underwent elective primary glioblastoma resection. For multivariate analysis to assess risk factors for RBC transfusion, logistic regression was conducted. The impact of RBC transfusion on overall survival was assessed using Kaplan-Meier analysis.

Results - In total, 36 (8.9%) patients received RBC transfusion. Preoperative anemia rate was significantly higher in transfused patients compared to patients without RBC transfusion (33.3 vs 6.5%; p<0.0001). Postoperative complications as well as hospital length of stay (LOS) (p<0.0001) were significantly increased in transfused patients compared to non-transfused patients. After multivariate analysis, risk factors for RBC transfusion were preoperative anemia (p<0.0001), intraoperative blood loss (p<0.0001), female gender (p=0.0056) and radiation (p=0.0064). Kaplan-Meier curves revealed that RBC transfusion and being elderly (age ≥75 years) were relevant for overall survival.

Discussion - RBC transfusion is associated with increased postoperative morbidity and mortality in patients undergoing elective primary glioblastoma resection. Preoperative anemia and intraoperative blood loss are major risk factors for RBC transfusion. Preoperative anemia management and blood conservation strategies are crucial in patients undergoing elective primary glioblastoma resection.

Quality and stability studies of red blood cell concentrates from umbilical cord blood compared to their adult counterparts

Fri, 02 Aug 2024 00:00:00 +0000

Background - Prematurity is a significant health issue due to its incidence and associated complications. Anemia is common in extremely preterm infants (EPI) and often requires transfusions. Red blood cells (RBC) from adult blood (AB) donors have been linked to oxygen-related complications in EPI, leading to the exploration of cord blood (CB) as an alternative source. However, standardization of CB-RBC manufacturing and comparison with AB-RBC characteristics are necessary before clinical studies can be conducted.

Materials and methods - This study investigated the quality and characteristics of leukoreduced, gamma-irradiated CB-RBC obtained using a commercial closed system from CB donations not meeting hematopoietic transplantation criteria. CB-RBC units were compared with AB-RBC units, both stored in saline-adenine-glucose-mannitol (SAGM). Various parameters, including hematological and biochemical characteristics, pH, 2,3-DPG levels, blood gases and potential toxicants, were evaluated during storage.

Results - CB-RBC units had acceptable initial quality parameters and a hematocrit (55±2%) comparable to AB-RBC. The main finding during storage was a faster rise in hemolysis compared to AB-RBC. Potassium (K+) significantly increased during storage in both sources. As expected, glucose levels decreased, and conversely, lactate levels increased, indicating similar patterns of anaerobic glycolysis during storage. pH decreased, affecting the oxygen dissociation curve due to reduced 2,3-DPG levels. After irradiation at 14 days of storage, CB-RBC were less stable as hemolysis and K+ significantly increased compared to AB-RBC at 24 hours. Phthalate concentrations, indicative of plasticizers, increased during storage, but significantly less in CB compared to AB-RBC. Most metals measured were within acceptable ranges.

Discussion - The quality of CB-RBC during storage is primarily influenced by levels of hemolysis and extracellular K+ content. Based on the analyzed parameters, we suggest that the expiration date for CB-RBC stored with SAGM should be set at 14 days, with transfusion occurring within <24 hours after irradiation.

Donor-specific anti-HLA antibodies (DSAs) in patients undergoing allogeneic hematopoietic stem cell transplantation from mismatched donors on behalf of GITMO and AIBT

Tue, 28 Jan 2025 00:00:00 +0000

Background - Antibodies directed against donor-specific HLA allele(s)/antigen(s)(DSAs) represent a known risk factor for hematopoietic stem cell transplantation (HSCT) engraftment. Still, the overall management needs to be standardized.

Material and methods - GITMO and AIBT ran a survey on DSAs in Italian Transplant Programs including mismatched HSCT performed between January 2014 and June 2017.

Results - One-thousand-thirty-three patients were proposed for the study, 804 were evaluable. Overall, 355 (44%) were screened: 91/355 (25.6%) showed anti-HLA antibodies, 23 DSAs (6.5%). Female gender and at least 4 previous pregnancies showed an impact on alloimmunization. Eleven patients with DSAs underwent desensitization. In seven cases no desensitization was employed. An alternative donor was selected for five patients. Neutrophil and platelet engraftment were obtained in 93.6% and 86.6% of the whole population, respectively, and were statistically associated with the absence of anti-HLA antibodies, ABO match, a higher number of infused nucleated cells and lack of a-GvHD. In addition, significant factors for platelet engraftment were the use of leuco-depleted transfusions, HLA match, younger age of the patient. Graft failure (GF) was associated with bone marrow stem cell source, and a lower number of infused CD34+. The detection of antibodies directed against both HLA classes, donor and patient age, the hematologic and molecular remission at HSCT, HLA match, ANC and PLTS engraftment, full donor engraftment within 28 days after HSCT, early and late GF, grade>II a-GVHD showed an impact on OS.

Discussion - Anti-HLA antibodies and DSAs were confirmed as risk factors affecting OS. DSAs were managed with various approaches resulting in stable engraftment in 81.9% of patients. Our study supports the clinical relevance of DSAs detection and management in mmHSCT. A standardized approach of DS is warranted.

The -72G>A nucleotide substitution impairs transcription of the ABO gene via reduction of promoter activity

Hang Lei, Jiewei Zheng, Dong Xiang, Hui Zhang, Xuefeng Wang, Xiaohong Cai — Thu, 21 Dec 2023 00:00:00 +0000

Introduction - The transcription of ABO gene is known to be regulated by a promoter and other transcription factor. Here, we identified two weak ABO subgroup alleles associated with -72G>A in the ABO promoter and explored the mechanisms that leads to A₃B and B₃ phenotype.

Materials and methods - Serology studies were performed to investigate the phenotype. The DNA sequence of ABO gene was analyzed to identified the genotype of the individuals. And the pedigree analysis was carried out to validate the hereditary background of the mutation and phenotype. The promoter activity was evaluated by reporter assays.

Results - Two individuals showed a discrepancy between the forward and reverse typing according to the serological results. The subject 1 was suspected to be A₃B phenotype and subject 2 was B₃ phenotype. According to the results of the direct sequencing and pedigree analysis, we identified a same mutation -72G>A in the ABO promoter on A allele in one A₃B individual and on B allele in a B₃ individual. The reporter assays showed the mutation -72G>A could reduce the promoter activity by 70% compared to the activity of the wild-type promoter and resulting in strong mixed-field agglutination.

Conclusion - Two “3” alleles were identified, and both associated with -72G>A in the ABO promoter. The substitution -72G>A can impair the transcription of ABO gene by reducing the promoter activity.

CD36 antibodies in isoimmunised African-origin pregnant women: three years experience in Spain

Thu, 08 Aug 2024 00:00:00 +0000

In this report we present a series of African-origin pregnant women with anti-CD36 isoantibodies. A case of Fetal/Neonatal Alloimmune Thrombocytopenia due to strong anti-CD36 isoantibodies, identified in 2020 in our reference laboratory, led us to hypothesize the potential implication of these antibodies in causing the weak red cell agglutination observed in the indirect antiglobulin test. Since January 2021, we have implemented the screening for CD36 antibodies for selected samples with a weak RBC pan-agglutination pattern and a suspected high-incidence specificity. In the past 3 years, we have detected anti-CD36 antibodies in seven pregnant women. In this report we describe the serological findings observed in these samples, present the clinical cases and discuss the recommendations for the management of these patients.