TRANSFUSION AND APHERESIS SCIENCE

Update on the measurement of "soluble angiotensin converting enzyme 2" in plasma and its emerging significance as a novel biomarker of cardiovascular and kidney diseases: A concise commentary
Amiral J and Ferol R
Angiotensin Converting Enzyme 2 has emerged as a major cell-surface enzyme receptor for controlling the Renin-Angiotensin-Aldosterone-System. The SARS-Cov-2 pandemics has focused a major interest on that cell-surface receptor. It is the virus entry door for cell infection, and when inside it can replicate and lead to cell destruction. In some physio-pathological conditions, ADAM 17 and TMPSSR2 enzymes can cleave ACE2 on the cell surface and release its extra-cellular domain into the blood circulation. Measurement of this soluble protein then becomes possible, preferentially in plasma, but also in serum. Clinical studies have shown that Soluble ACE2 is an emerging biomarker for cardiovascular and kidney diseases and it could be of prognostic value for heart failure and kidney dysfunctions. In Covid-19 its diagnostic value is controversial, and the various studies lead to different conclusions. Many laboratory assays have been reported for the measurement of this biomarker. They concern enzymatic assays, aptamer methods, or immunoassays, either chemiluminescent or ELISA. Normal and pathological plasma concentrations reported with the various assays yet lack standardization and are very heterogenous. Recently introduced immunoassays tend to yield more compliant results despite variations due to the assay design and calibration, or the antibody targeted epitopes and reactivity. This article reports an ELISA designed with affinity purified rabbit polyclonal antibodies, obtained with recombinant ACE2 and calibrated with the recombinant protein in plasma. This assay has a global reactivity with the various ACE2 protein epitopes. Assay performance characteristics, and values measured in normal populations are presented. Availability of optimized ELISAs can contribute to a better harmonization of sACE2 measurements in plasma, and confirm its clinical significance as biomarker.
The 2024 International Survey of Platelet Products and Practice and two related manuscripts in this issue of Transfusion and Apheresis Science
Nollet KE and Ohto H
Correlation between blood parameters in the early and later stages of pregnancy: A retrospective study
Ibrahim N, Alziyadi SH, Yaacob NM, AlGhamdi A, Alanazi M, Alfaifi J, Umah JBJ, Doheir M, Hamid OA and Alazzam M
Anemia is common in pregnant women and is associated with various maternal and fetal complications. However, the effect of fluctuations in hemoglobin levels during pregnancy on birth outcomes remains unclear. Therefore, we investigated the association between maternal hemoglobin levels at different stages of pregnancy and delivery outcomes.
Considerations on risk mitigating strategies for bacterial contamination of platelet concentrates - The Dutch perspective
van der Meer PF, Novotny VMJ and Klei TLR
Due to their storage at room temperature, platelet concentrates are at risk for bacterial outgrowth if the unit is contaminated. Nowadays, various mitigation strategies are available, including bacterial screening and pathogen inactivation. Since pathogen inactivation technologies impact the clinical efficacy of the platelets, including but not limited to lower increments after transfusion and more significant bleeding, a balance needs to be struck between the safety and efficacy of platelet transfusions. In this Brief Review, we discuss the current situation in the Netherlands.
Pathogen-reduction technology, good in more than one way for cellular blood components, is replacing irradiation
Flegel WA
Clinical application of pathogen-reduction technology (PRT) is often restricted to platelet and non-cellular components, representing a minor fraction of the overall blood supply. The greatest benefit for patient safety may eventually derive from PRT in red cells, which is still unavailable for routine use. PRT is more effective to inactivate leukocytes than current irradiation, particularly pertinent for Japan with the only universal irradiation of cellular blood components. Elsewhere, only vulnerable patient cohorts are receiving irradiated cellular components. Blood components treated with approved PRT systems are exempt from irradiation if the patient requires irradiated components. Transfusion medicine has a strategic opportunity to develop and eventually utilize PRT for all cellular components, other than hematopoietic progenitor cell products. PRT would then enable leukocyte inactivation for 100 % of the blood supply, beneficial for transfusion safety in all patients.
Mononuclear cell recruitment during extracorporeal photopheresis: Partial results of a phase 1/2 randomized clinical trial in multiple sclerosis
Castillo-Aleman YM, Villegas-Valverde CA, Ventura-Carmenate Y, Al-Kaabi FM, Lumame S, Castelo C, Mir R, Brylev L, Atieh M, Haider MT and Bencomo-Hernandez AA
Despite the routine clinical use of extracorporeal photopheresis (ECP) for the last decades, there has been no sufficient investigation on the intra-apheresis dynamics of mononuclear cells (MNCs).
The 2024 international survey of platelet products and practice
Ohto H, Flegel WA, van der Meer PF, Ngoma AM, Nollet KE, Choudhury N, Legler TJ and
Previously, two international surveys have addressed the wider application of platelet collection by apheresis technology and practical issues of platelet transfusion.
Immunoglobulin use - Helpful treatment or panacea?
Sibinga CTS
CAPRIN2 RNA-binding protein contributes to balance erythroid production: Implications in the fine-tuning of proteostasis during erythropoiesis
Jaiteh Z, van der Linden R, Kong-A-San J, Maas A, Philipsen S, Grosveld F and Gutiérrez L
Erythropoiesis is a process that requires tight control of gene transcription, mRNA stability, and protein synthesis and degradation. These regulatory layers adapt dynamically to developmental needs and physiological stresses, ensuring precise control of erythroid production. Ribosomopathies, such as Diamond-Blackfan anemia (DBA), are characterized by defects in ribosome function. Zooming in on erythroid precursors, ribosomopathies lead to dysregulated translation of mRNAs encoding specific and essential erythropoietic genes, including master transcription factors such as GATA1. This causes defective maturation and increased apoptosis of erythroid progenitors, and consequently, anemia. Beyond ribosomal proteins, RNA-binding proteins have been put forward as an additional and targeted checkpoint regulating cellular proteostasis. CAPRIN2, which is present in neurons and erythroid cells, is one such RNA-binding protein, involved in RNA translation regulation and its levels rise during terminal erythroid differentiation. Overexpression of CAPRIN2 in Chinese hamster ovary (CHO) cells causes reduced growth, cell cycle arrest, and apoptosis. Here, we demonstrate that GATA1 potentially regulates Caprin2 transcription, and that Caprin2 loss boosts erythroid production and maturation during gestation and adulthood, a phenomenon that is enhanced in situations of stress erythropoiesis. Our results provide new insight into the role of CAPRIN2 in erythropoiesis. We hypothesize that it regulates the translation of key mRNAs during erythropoiesis. We propose that CAPRIN2 is involved in the balance of erythroid production and that its manipulation may control erythroid production, offering a potential and promising approach to manage altered erythropoiesis.
Editorial commentary
Seghatchian J
Weak D testing might be discontinued for RhD-negative blood donors with C and E negative phenotypes in the Indian population
Sinha A, Basu S, Basu D, Reddy M, Rophina M, Scaria V and Datta SS
Although serological testing to determine weak D status using the antihuman globulin reagent has been phased out for RhD-negative donors in many countries after the availability of RHD genotyping, it is routinely performed in India. However, weak D testing is a resource-intensive and time-consuming process. We devised a new algorithm for weak D testing in RhD-negative blood donors by performing CcEe phenotyping followed by weak D testing in only C+ and/or E + samples and compared it with the existing protocol in terms of time and cost-effectiveness.
Prevalence of transfusion transmitted infections by mode of donation and remuneration status among blood donors in Georgia, 2018-2023
Shermadini K, Bloch EM, Shadaker S, Alkhazashvili M, Chitadze N, Surguladze S, Tskhomelidze I, Getia V, Adamia E, Tohme RA and Gabunia T
Global reform of blood transfusion services is underway in the country of Georgia. New legislation mandates exclusive collection of blood from non-remunerated blood donors in Georgia by July 2025. Retrospective data (2018-2023) from the National Blood Donor Registry were analyzed. The prevalence was calculated for human immunodeficiency virus (HIV) antigen/antibody (Ag/Ab), hepatitis C virus antibody (anti-HCV), hepatitis B surface antigen (HBsAg). Results were stratified by remuneration status and mode of donation. Descriptive analysis was performed to elucidate differences in positivity by year and donor type. During 2018-2023, there were a total of 548,530 donations from 221,492 blood donors in Georgia; 68.3 % of donors were male and the median age was 34 years (interquartile range: 2644). Overall, 17.0 % were paid, 24.9 % were replacement, 47.4 % were voluntary non-remunerated blood donors (VNRBD), and 10.7 % had ≥ 2 donations of varying remuneration type. Paid donors had an average of 2.5 donations per year, compared to 1.0 for replacement, and 1.1 for VNRBDs. During 2018-2023, the proportions of paid donors decreased (38.8-22.1 %); the proportions of replacement (19.1-26.0 %) and VNRBDs (38.7-48.3 %) increased. Among first-time donors, prevalence decreased during 2018-2023 for anti-HCV (2.0-0.9 %) but were stable for HBsAg (range: 1.9 %-2.1 %) and anti-HIV (range: 0.1 %-0.2 %). Among repeat donors, prevalence of anti-HCV decreased (from 0.3 % to 0.2 %) while rates were stable for anti-HIV (0.04 %-0.1 %), and HBsAg (0.1 % in all years). The findings underscore the importance of donor retention in concert with efforts to attain exclusive VNRBD.
Hidden in plain sight: Detecting rare naturally occurring anti-K antibody in a blood donor
Baldota R, Kakkar B, Ketkar S and Patil M
Red cell alloimmunisation is commonly reported among pregnant, transplant and multitransfused patients, whereas it is a fairly rare occurrence in the healthy general population. We report a rare case where we detected naturally occurring anti-K antibody in a healthy male whole blood donor during routine antibody screening.
A novel allele of B(A) blood group detected in a donor and a patient during a retrospective review of ABO group anomalies in a tertiary hospital
Suksard K, Millard GM, Teravichitchainan U, Permpikul P and Kittivorapart J
ABO discrepancies, inconclusive results between forward and reverse typing, are one of the significant challenges encountered in transfusion medicine. Their frequency and etiologies can vary among ethnicities. This study aimed to characterize ABO discrepancies in a Thai population.
The prevalence and pattern of alloimmunization in patients with sickle cell disease in Abuja, Nigeria
Chinedu O, Hezekiah IA, Akinloye OB, Samuel A, Ofakunrin AO, Ogbe OP, Amaechi R and Nnodu OE
One of the components of comprehensive care and interventions in managing patients with sickle cell disease (SCD) is red blood cell transfusion. This has helped in reducing the morbidity and mortality associated with SCD. Individuals who undergo multiple red cell transfusions are faced with alloimmunization which makes it difficult to source compatible blood for them. This often leads to haemolytic reactions and sometimes death of the patients. In this study, we determined the prevalence and pattern of alloimmunization in patients with SCD.
A serological and molecular study on a case of Rh blood group mosaicism
Yin M, Huang X, Pian J, Ma J, Hong X, Chen X and Xu X
Mosaicism refers to the presence of two or more genetically different cell lines within a single individual, the majority of which are accidentally discovered through routine blood group identification. Here, we report one case of Rh blood group mosaicism in a 10-year-old Chinese male.
eHealth technologies for enhancing blood donor knowledge and behaviour: A PRISMA scoping review
Dei EN and Leitch S
Blood donor information and education are pivotal in improving knowledge and encouraging positive behaviours towards blood donation. Their impact of utilizing eHealth technologies on self-efficacy presents new opportunities to improve knowledge and encourage people to donate blood.
Transfusion-associated circulatory overload: A retrospective audit of risk assessment practices in a large teaching hospital
Badu SA
Transfusion-associated circulatory overload (TACO) is a serious transfusion reaction and a leading cause of transfusion-related mortality. It is recommended that all patients requiring blood transfusion should be assessed for the risk of TACO. The 2022 Serious Hazards of Transfusion (SHOT) report indicated a TACO risk assessment compliance rate of 35.6 % across the United Kingdom. This retrospective audit evaluated the TACO risk assessment compliance of a large teaching hospital in Northwest England.
Precision diagnostics in Transfusion Medicine: Advancing accuracy in Bombay blood group typing through molecular methods
Shastry S, Chopra A, Liew YW, Millard G, Chenna D, Mohan G and Madkaiker D
Integration of precision diagnosis in Immunohaematology and Transfusion Medicine has led to the development of more refined blood typing and crossmatching techniques, ensuring improved accuracy of blood group determination, thereby reducing the incidence of transfusion reactions and enhancing patient safety. It can also help resolve complex discrepancies noted in serological testing methods.
Twenty years of the four-factor prothrombin complex concentrate Octaplex/Balfaxar: A narrative review
Karkouti K, Gareis M, Li C, Brandstätter H, Pichotta A, Shah TM and Goldstein JN
Prothrombin complex concentrate (PCC) is used to boost thrombin potential, support clot formation, and aid in the treatment and prophylaxis of bleeding. The two main forms of PCC are three-factor (3 F-PCC; comprising coagulation factors II, IX, and X) and four-factor (4F-PCC; factors II, VII, IX, X), which contain 25 times the clotting factors found in human plasma. This narrative review summarizes published efficacy and safety data on one 4F-PCC (Octaplex/Balfaxar, Octapharma) within its recognized uses and explores potential applications across different clinical contexts. Clinically available for > 20 years, Octaplex/Balfaxar is supplied as a freeze-dried powder for reconstitution and intravenous infusion. This 4F-PCC contains non-activated forms of coagulation factors as well as anticoagulant proteins C and S, potentially affording a balanced hemostatic effect and mitigating thrombosis risk. Production involves two virus inactivation/removal steps: solvent/detergent treatment and nanofiltration. 4F-PCC is approved for acquired deficiency of vitamin K-dependent clotting factors, such as those induced by vitamin K antagonists (VKAs, e.g., warfarin), and for congenital deficiency of factors II and X. Five published trials in 444 adult patients demonstrated the efficacy of 4F-PCC in VKA reversal, reducing the international normalized ratio (INR) with only two potentially treatment-related thrombotic events reported. While 4F-PCC dosing is currently indicated to be INR-guided, emerging evidence supports fixed dosing as an alternative to conventional weight-based dosing for VKA reversal. Recent guidelines support 4 F-PCC use for direct oral anticoagulant-associated bleeding, cardiac surgery and trauma/emergencies. Ongoing studies will further clarify the efficacy and safety of 4 F-PCC beyond its approved indications.
Etoposide + cytarabine + pegfilgrastim versus cyclophosphamide + G-CSF for stem cell mobilization in patients with poorly mobilized multiple myeloma and lymphoma
Cheng Y, Xu S, Pei R, Chen D, Du X, Li S, Zhuang X, Zhuang H, Fang Y, Wu M, Ye P and Lu Y
In multiple myeloma (MM) or lymphoma with poor mobilization, the combination of etoposide, cytarabine (Ara-C), and pegfilgrastim (EAP) appears to have higher mobilization efficacy than cyclophosphamide (Cy) plus granulocyte colony-stimulating factor (G-CSF) (CG) regimens. The purpose of this study was to examine whether there were differences in efficacy and toxicity between the two mobilization regimens.