Introduction: Although the African Union Development Agency-New Partnership for Africa’s Development (AUDA-NEPAD) has initiated activities to support the establishment of a harmonized regulatory framework for in vitro diagnostics (IVDs), including those for testing blood and blood components, challenges such as limited infrastructure and insufficient technical expertise remain. The Global Health Protection Programme (GHPP) project BloodTrain, which seeks to strengthen regulatory systems for blood and blood products in Africa, addressed this by organizing an advanced workshop focused on IVD technical assessment. Data on national IVD regulatory systems were also collected through a structured questionnaire. Furthermore, a survey was conducted to evaluate both the perceived usefulness of the training and the applicability of the tools provided. Methods: An advanced training was conducted for personnel from 14 African national regulatory authorities who possessed prior knowledge and experience in the assessment of IVDs. The participants were also granted access to online courses on IVD technical file assessment. The workshop comprised theory and case study exercises by experts from TÜV Rheinland and BloodTrain, complemented by presentations from the participants on their national IVD regulatory systems. These presentations led to the development of a questionnaire to achieve a comparison of these regulatory systems. Results: In the survey, the workshop content resulted in a mean score of 4.5 on a 5-point scale. Lesser mean scores on workshop duration and previous knowledge to follow the workshop underline the need for additional training on IVD assessment. The comparative assessment of the regulatory criteria for IVDs collected by a post-workshop questionnaire showed the majority of the participating countries already had some level of regulation on IVDs, but there are still gaps that need to be addressed. Conclusion: The advanced IVD workshop provided well-appreciated training on IVD dossier assessment and also delivered understanding of the heterogenous regulatory landscape in the participating countries. While the questionnaire suggested that in most of the participating countries regulatory systems for IVDs are already in use, the survey painted a differentiated picture with heterogenous preexisting knowledge and the expectation that the trained content will be helpful in the future.
Introduction:Successful bone regeneration after dental and craniofacial reconstruction can present a significant clinical challenge. In this study, we investigated whether the regenerative potential of human periosteum-derived stromal progenitor cells (PDCs) depends on their anatomical origin. Methods:Paired periosteum samples were collected from jaw and appendicular bones (fibula, femur, or iliac crest) of five donors and expanded in a xeno-free, platelet lysate-supplemented medium. All cultures exhibited a typical fibroblastic morphology and a uniform stromal immunophenotype (≥95% CD73/90/105 and ≤2% CD45/14/19/HLA-DR). PDCs were tested in a 3D cartilage disc formation assay after seeding on collagen-coated transwell inserts or on transferrable porcine collagen membranes. Results:Appendicular-derived PDCs consistently formed stable, cartilage-like 3D discs with a mean weight of 14.7 mg and a range of 8.8-23.6 mg, whereas jaw-derived PDCs produced contracted, irregular aggregates. Histological and molecular analyses confirmed greater proteoglycan deposition and higher COL2A1 expression in appendicular-derived PDCs, indicating superior intrinsic chondrogenic potential. Culturing jaw-derived PDCs on porcine collagen membranes did not enhance their differentiation capacity. Conclusion:Our findings demonstrate that the chondrogenic potential of PDCs is strongly determined by their anatomical origin. Therefore, selecting the appropriate periosteal source, combined with optimized biomaterials, is crucial for achieving predictable and efficient bone regeneration.
Introduction: Von Willebrand disease (vWD) type 2N is a hereditary bleeding disorder that is based on a structural defect in the region of the von Willebrand factor (vWF) that binds to coagulation factor VIII with high affinity. The underlying mutations cause impaired adhesion of vWF to coagulation factor VIII, which becomes prematurely degraded in the blood circulation resulting in a coagulation factor VIII deficiency that can only be distinguished from mild hemophilia A using specialized assays. Therefore, the diagnosis of vWD type 2N can be challenging. Case Presentation: Here, we report on two sisters with reduced coagulation factor VIII activities of 20-30 % and a mild bleeding tendency. While both siblings presented with normal vWF activity and antigen, they were each diagnosed with a decreased vWF:FVIIIC binding activity. Subsequent genetic testing revealed the same two heterozygous variants of the VWF gene in each of the sisters, namely the common vWD type 2N mutation p.R854Q and a variant of uncertain significance p.S801N, both located in exon 18-20. The mother was heterozygous for the p.R854Q variant but did not carry the p.S801N variant while none of the 2 genetic variants were detectable in a third sister. Notably, both the mother and the third sister presented with a normal coagulation factor VIII activity. Conclusion: Our case report suggests a novel compound heterozygous form of vWD type 2N in two sisters based on a pathologic vWF:FVIIIC binding assay in combination with genetic testing that yielded the common p.R854Q variant as well as a novel genetic variant p.S801N.
Introduction:Accurate prediction of blood product demand is essential for maintaining adequate supply while minimizing wastage. Artificial intelligence (AI) and machine learning (ML) approaches have emerged as promising tools for transfusion demand forecasting across multiple scales, ranging from individual patients to regional supply chains. This review provides a structured overview of AI applications in blood banking, organized by prediction scope and clinical objective. Methods:We conducted a systematic review following PRISMA 2020 guidelines, searching PubMed and Scopus for studies published between January 2015 and December 2025. Studies applying AI or ML to transfusion demand prediction were included. We organized findings into a four-tier framework based on prediction scope and clinical goal and systematically compared technical approaches. Results:Out of 535 identified records, supplemented by a targeted search during peer review, 24 studies met inclusion criteria. The four-tier framework revealed distinct prediction challenges: (1) patient-individual prediction (goal: improve individual care quality) achieved areas under the curve (AUCs) of 0.45-0.97 across five studies for 24-h to 72-h prediction, (2) procedure-specific models (goal: optimize surgical blood ordering) achieved AUCs of 0.70-0.91 across six studies, (3) facility-level optimization (goal: reduce wastage and shortages) approximately halved platelet outdating rates and achieved mean absolute percentage errors as low as 4.18% across eight studies for daily to weekly forecasting, and (4) regional forecasting (goal: secure long-term supply) achieved R 2 values up to 0.85 across five studies for monthly forecasting. Deep learning excelled for temporal patterns in individual patients, while traditional statistical methods (ARIMA, SARIMA) proved effective for aggregated regional forecasting, where deep learning approaches showed no consistent advantage over simpler models. Prediction horizons varied by blood product: 3-7 days for platelets versus weekly to monthly for red blood cells. Conclusion:AI-driven demand prediction offers substantial potential to improve blood supply management across all tiers of the blood supply chain. The choice of modeling approach should be guided by the prediction scope, available data infrastructure, and specific clinical objectives. Standardized external validation remains critical for clinical deployment.
Background: The transfusion of blood is an indispensable and irreplaceable component of contemporary medicine. Nevertheless, particularly in patients with very rare blood groups, the lack of blood products still represents a significant health problem on a global scale. In order to address this shortage, strategies for producing artificial blood substitutes have been pursued for a period of time exceeding 60 years. Summary: This overview synthesizes the latest advancements in the field of erythropoiesis, encompassing the expansion strategies for erythrocyte cells, the diverse sources of ex vivo-expanded erythrocytes, the impediments to clinical implementation, the prospective applications, and alternative blood products. Conclusions: Ex vivo generation of red blood cells (RBCs) has advanced from proof-of-concept to early clinical testing, yet scalable, cost-effective manufacturing remains unresolved. Continued optimization of cell sources, immortalized progenitor lines, and bioreactor technologies, alongside deeper mechanistic insights into terminal erythropoiesis and enucleation, will be key. Integrating these advances within rigorous regulatory frameworks could ultimately enable standardized, universally compatible RBC products.
Introduction:"Wrong blood in tube" (WBIT) describes the discrepancy of patient identity between tube label and tube content. WBIT events can lead to an incompatible transfusion and may have serious consequences for the patient. There are currently no comprehensive evaluations or analyses of WBIT events in Germany. This study is conducted as a feasibility study. The detected WBIT (dWBIT) events from 2020 to 2023 were retrospectively recorded and analyzed. Methods:The reporting of this study is guided by the Checklist for Reporting of Survey Studies (CROSS). It is not mandatory to report WBIT events to a central supervisory authority in Germany. Therefore, a cooperation with four blood establishments (BEs) took place. The data were collected using a data collection form. The survey contains a total of 14 questions about each dWBIT event. A database was created in FileMaker 2023 for data storage and plausibility checks. Results:In the 4 years under review, there were a total of 125 dWBIT events in the four cooperating BEs. The rate of dWBIT events results in an overall rate of one dWBIT per 4,530 blood group determinations. Frequencies varied between emergency room (1:6,897), outpatient ward (1:3,866), regular ward (1:2,564), and intensive care unit (1:863). The main reason for the error was incorrect labeling of the collection tube (19%) and blood sample taken from the wrong patient (32%). In most cases, the error was noticed in the laboratory (94%), and in 5% directly after the sample was taken. dWBIT events occurred in 87% of patients with a known blood group and in 13% of patients with a first blood group determination. The time of sampling for blood typing (time of day, day of the week, or weekend) had no influence on the dWBIT rate. None of these WBIT cases led to an ABO-incompatible transfusion. Conclusion:The study examines the frequency of dWBIT incidents in Germany for the first time and shows that these cases continue to represent a relevant risk, especially with regard to incompatible transfusions. Measures to minimize risk could include improving the training of transfusion staff in combination with IT-based identification and two independent blood samples for blood group typing.
Introduction:While neonates may suffer from alloimmune or secondary autoimmune diseases caused by placental transfer of maternal antibodies, primary neonatal autoimmune disease is extremely rare. Case Presentation:We present a newborn girl with fetal-onset autoimmune disease, featuring prenatal hydrothorax, progressive Coombs-positive autoimmune hemolytic anemia, and autoimmune thrombocytopenia secondary to autoantibodies against glycoprotein IIb/IIIa, which were not present in the mother. Red blood cells and platelets were repeatedly transfused during the first 5 weeks after birth. At 6 months of life, the infant displayed elevated liver enzymes and vitamin K deficiency coagulopathy due to giant cell hepatitis. There was a partial response to systemic steroids, intravenous immunoglobulins, and anti-CD20 antibodies. Complete genome analysis failed to detect a genetic cause. Conclusion:This rare case indicates that infantile Evans syndrome can already evolve during fetal development.
Introduction:The objective of this study was to compare the efficacy and safety of amotosalen/ultraviolet A pathogen-reduced platelet components (PRPCs) with conventional platelets for transfusion of term and preterm neonates who are vulnerable to transfusion-transmitted infections and transfusion associated graft vs. host disease. Safety and efficacy of concomitant use of PRPC and phototherapy (PT) treatment with a specific focus on a large cohort of premature neonates have not been investigated before. Methods:In this retrospective cohort study, medical records were audited for gestational age, birth weight, number of transfusions, platelet count and transfusion increments, maximum bilirubin, PT, and transfusion-related adverse events. Term and preterm neonates were transfused with conventional PC (CPC) during a period of 72 months (2005-2010) before PRPC and during 57 months after PRPC implementation (2011-2015). Fresh frozen plasma (FFP) and red blood cells (RBCs) were used as surrogate hemostasis indicators. Results:In the first cohort, 92 neonates received 180 CPC and in the second cohort 99 neonates received 225 PRPC. Similar proportions of patients in each cohort had bleeding (central nervous system 18% vs. 19%, pulmonary 3.0% vs. 3.3%). The gestational ages and birth weights were similar (33.1 vs. 33.0 weeks and 1.8 kg for both). The proportion of multiple births (twins, triplets) was significantly higher in the PRPC cohort (27 vs. 6). Neonates treated with PRPC received more concomitant PT treatments (3.8 vs. 2.4). There were no differences in PC, FFP, or RBC units transfused. Mean platelet count increments were not different (PRPC: 82.9 ± 45.1 vs. CPC: 95.9 ± 53.0). No patients had transfusion-related phototoxicity. Conclusion:The study demonstrated PRPC efficacy and safety for term and preterm neonates with or without concurrent PT.
Introduction:Autologous serum eye drops (ASEDs) are used to treat patients with dry eye syndrome. ASED is manufactured by fractionation of autologous whole blood of concerned patients and usually stored under home freezing conditions. Methods:We analyzed sterility, particle number, protein concentration, and stability of 14 growth factors in ASED for 148 days at -10°C. Results:Total protein concentration was constant showing no significant degradation as assessed by 1D-SDS-PAGE. Slightly increased concentrations of angiopoietin-2, vascular endothelial growth factor, platelet-derived growth factor, and hepatocyte growth factor were observed, while stem cell factor concentration showed only a modest decrease. Conclusion:Our data support the feasibility to store ASED for patient use under usual home freezing conditions for up to 148 days.
Introduction Although the African Union Development Agency–New Partnership for Africa’s Development (AUDA-NEPAD) has initiated activities to support the establishment of a harmonized regulatory framework for in vitro diagnostics (IVDs) including those for testing blood and blood components, challenges such as limited infrastructure and insufficient technical expertise remain. The Global Health Protection Programme (GHPP) project BloodTrain, which seeks to strengthen regulatory systems for blood and blood products in Africa, addressed this by organizing an advanced workshop focused on IVD technical assessment. Data on national IVD regulatory systems were also collected through a structured questionnaire. Furthermore, a survey was conducted to evaluate both the perceived usefulness of the training and the applicability of the tools provided. Methods An advanced training was conducted for personnel from 14 African national regulatory authorities who possessed prior knowledge and experience in the assessment of in vitro diagnostics (IVDs). The participants were also granted access to online courses on IVD technical file assessment. The workshop comprised theory and case study exercises by experts from TÜV Rheinland and BloodTrain, complemented by presentations from the participants on their national IVD regulatory systems. These presentations led to the development of a questionnaire to achieve a comparison of these regulatory systems. Results In the survey, the workshop content resulted in a mean score of 4.5 on a 5-point scale. Lesser mean scores on workshop duration and previous knowledge to follow the workshop underline the need for additional training on IVD assessment. The comparative assessment of the regulatory criteria for IVDS collected by a post-workshop questionnaire showed the majority of the participating countries had already some level of regulation on IVDs, but there are still gaps that need to be addressed. Discussion The IVD workshop provided well-appreciated training on IVD dossier assessment, and also delivered understanding of the heterogenous regulatory landscape in the participating countries. While the questionnaire suggested that in most of the participating countries regulatory systems for IVDs are already in use, the survey painted a differentiated picture with heterogenous preexisting knowledge and the expectation that the trained content will be helpful in the future.
Introduction:The aim of this study was to investigate the clinical consequences of anti-D and non-anti-D antibodies undetected at screening in the first trimester for hemolytic disease of the fetus and newborn (HDFN). Methods:This prospective study (conducted from 2010 to 2024) included pregnant women with negative first-trimester antibody screening for red blood cell (RBC) antibodies but positive later in pregnancy for clinically significant antibodies anti-D and non-anti-D. We analyzed the incidence of antibodies, DAT of the newborn, and the treatment and outcomes of HDFN. Results:In study period, 61,200 pregnant women were tested, of which 11,000 were RhD-. In 32 cases, anti-D antibodies were initially detected at the repeated screening (28th/34th week of pregnancy or to 24 h post-delivery). All women have given birth to D+ child, of which 50% had a positive DAT. Four of them had early jaundice. In two cases, blood transfusion was required due to anemia. The incidence of anti-D antibody undetected at first trimester was 29/10,000 in D- women. Anti-D antibody caused severe HDFN in 1.8/10,000. Non-anti-D antibodies have been detected on repeated screening in seven cases, anti-c (N = 5), anti-E (N = 1), anti-C (N = 1). All seven neonates were antigen positive, three of which had positive DAT due to anti-c antibodies. The neonates with positive DAT had early jaundice and needed phototherapy, but there were no cases of severe HDFN in this group. Conclusion:First-trimester screening for RBC antibodies detected all cases of severe HDFN caused by non-anti-D antibodies out of 61,000 pregnant women tested.
Background: Platelet products derived from whole blood include platelet-rich plasma (PRP), platelet-rich fibrin (PRF), platelet lysate (PL), and platelet-derived extracellular vesicles (pEVs). Such products have been utilized for hemostatic purposes and regenerative medicine. Poor shelf life, high cost of storage, immune risk, and constant need for adequate donors have led to the desire for biomaterials that mimic platelet function. Artificial platelets, such as platelet-membrane coated nanoparticles (NPs), platelet-like particles, SynthoPlate, and GRGDS-PEG-coated polyurethane NPs, have been designed to mimic platelet functionality and aid in hemostasis. Summary: Platelet product and artificial platelet function can be further leveraged for regenerative medicine and wound healing as they interact with activated platelets and fibrin at the region of interest, highlighting their therapeutic potential. Example regenerative applications of both platelet products and artificial platelets include osteogenesis, angiogenesis, soft tissue and dermal healing, and drug or cell delivery. Key Messages: Some platelet products have reached clinical trials, but most of the biomaterial based approaches are still in preclinical testing. Research into their regenerative and wound healing capabilities is novel for the field, but the products show tremendous promise in biomedical applications beyond hemostasis.
Introduction: Twin Anaemia Polycythaemia Sequence (TAPS) is a recognised complication of monochorionic (MC) twins due to abnormal placental vasculature. Determining the rheology involved within the abnormal placental vasculature may help in identifying the optimum treatment option. Case Presentation: We describe a case of TAPS which was treated via intrauterine transfusions (IUTs) with partial exchange transfusions (PETs) in which additional haemoglobin electrophoresis (HbEp) testing was performed on cordocentesis samples taken before and after intrauterine transfusions and partial exchange transfusions for the donor and recipient twin, respectively. The aim was to assess the flow dynamics from the donor to recipient twin. No differences in hemoglobin A were found in the polycythemic twin after 30 minutes of IUT of the anemic co-twin but within 13 days of first transfusion greater than a 3-fold rise in adult Hemoglobin A was apparent. Within 5 days of second treatment a further 9% rise in Adult Hemoglobin A was encountered. Conclusion: The use of HbEp testing in this case provided preliminary insights into the fluid dynamics involved in TAPS, however, further studies are required to achieve better understanding.
Introduction: Hemolytic disease of the fetus and newborn (HDFN) is a potentially life-threatening condition caused by maternal alloimmunization against fetal red blood cell (RBC) antigens. While most cases involve well-characterized antibodies such as anti-D, anti-c, or anti-K, antibodies against low-prevalence antigens (LPAs) — particularly those within the MNS blood group system — remain underrecognized and underreported. Case Presentation: We report a case of maternal alloimmunization against the paternally inherited low-prevalence antigen MUT (MNS35), carried on a hybrid glycophorin (GYPA*19, GP.Hut), across three pregnancies. The first pregnancy ended in fetal demise due to severe anemia at 33 weeks of gestation (WG). In a subsequent twin pregnancy, both neonates presented with severe HDFN after emergency cesarean section at 31 WG. Anti-MUT antibodies were identified in maternal plasma and neonatal eluates, with a high monocyte index observed in functional testing using paternal and GP.Mur-positive RBCs. Sequencing demonstrated the presence of the GYPA*19 (GYPA*Hut) allele in both infants. The two neonates had favorable outcome after exchange transfusion and intensive phototherapy. A third pregnancy was closely monitored. Anti-MUT antibodies remained stable at 1/32 between 20 and 36 WG. The patient delivered a healthy newborn without anemia. After birth, the child was tested GP.Hut negative. Conclusion: This case supports the pathogenicity of anti-MUT as a cause of severe HDFN. It underscores the diagnostic challenges posed by antibodies against LPAs and highlights the importance of extended serological, molecular, and functional testing. Crossmatching maternal plasma with paternal RBCs and systematic evaluation of serological discrepancies can reveal otherwise undetectable alloantibodies. Early identification, functional assessment, and multidisciplinary management are key to optimizing outcomes in pregnancies complicated by rare RBC alloimmunization. Anti-MUT should be considered a clinically significant antibody with the potential to cause severe HDFN, warranting proactive perinatal surveillance.
Introduction: Cold agglutinin disease is a rare autoimmune hemolytic anemia, a low-grade lymphoproliferative disease. Our objective was to determine the occurrence of cold agglutinin disease among patients with autoimmune hemolytic anemia and to map its specific characteristics, with a particular focus on thromboembolic complications. Methods: In a Hungarian hematology center, we retrospectively studied clinical data, laboratory parameters, and therapy of 84 patients with autoimmune hemolytic anemia. Results: A total of 17% of patients had cold autoimmune hemolytic anemia, with 8 patients fulfilling the criteria for cold agglutinin disease and 7 patients having cold agglutinin syndrome. Most patients were older than 70 years, and the disease was more common in women (49 women, 35 men). Here, 71% of patients with CAD were administered rituximab, while some received additional chemotherapy. The 10-year survival rate was significantly worse in cold-type hemolytic anemia than in warm-type autoimmune hemolytic anemia (66.7% vs. 82.4%). Congenital and acquired causes of thrombophilia were examined in patients with severe hemolysis (hemoglobin <60 g/L, LDH >1.5× the upper limit of normal) and in cases with thromboembolic complications. Conclusion: This is the first case series from a country in Central Eastern Europe with a four-season climate, demonstrating the occurrence of cold autoimmune hemolytic anemia. Overall survival was influenced by age, type of hemolytic anemia, and total bilirubin level during presentation. Inherited and acquired thrombophilia risk factors and antiphospholipid antibodies were detected in more patients with cold autoimmune hemolytic anemia than those with warm autoimmune hemolytic anemia.
Background: Recent advances in haemophilia A and B treatment, including extended half-life (EHL) factor concentrates, factor VIII (FVIII)-mimetic antibodies, gene therapies, and rebalancing agents, have substantially improved prophylaxis and bleed prevention. However, these therapeutic innovations have also introduced significant analytical challenges for laboratory monitoring. Conventional coagulation assays, particularly one-stage clotting assays and chromogenic substrate assays, frequently show assay-dependent discrepancies when applied to modified factor molecules, transgene-derived coagulation factors, or nonfactor therapies. In addition, antidrug antibodies (ADAs) against replacement products and novel biologics require adapted diagnostic strategies. Summary: This review discusses current laboratory challenges associated with modern haemophilia therapies. The effects of EHL factor concentrates on FVIII/FIX activity measurements, assay discrepancies in gene therapy, and assay interferences caused by FVIII-mimetic antibodies are summarized. Furthermore, analytical considerations for rebalancing therapies targeting antithrombin or tissue factor pathway inhibitor are addressed. The review also outlines current approaches for inhibitor and ADA testing in the setting of modified factor products and nonfactor therapies. In addition, the role of global haemostatic assays, particularly thrombin generation assays (TGAs), as emerging tools for integrative assessment of coagulation potential is discussed. Key Messages: Modern haemophilia therapies substantially affect the performance and interpretation of conventional coagulation assays and require therapy-specific analytical strategies. Reliable laboratory monitoring depends on detailed knowledge of assay characteristics, therapy-associated interferences, and appropriate methodological adaptations. Although global assays such as TGAs are increasingly investigated as integrative monitoring tools, further harmonization and clinical validation are required before widespread routine implementation.
Introduction: Preterm neonates are at high risk for complications, and inflammation has been implicated in many of these pathologies. ABO incongruency occurs when the maternal and neonatal blood types are different and may cause complications when the mother creates antibodies against neonatal blood type antigens. In this study, we investigated whether preterm neonates with type A or B blood born to mothers with type O blood (ABO incongruent) had higher rates of neonatal complications than neonates with type O blood born to mothers with type O blood (ABO congruent). We hypothesized that preterm neonates who were ABO incongruent would have a higher incidence of neonatal morbidity. Methods: This was a population-based single-center retrospective cohort study of 371 preterm neonates whose mothers had O blood type, were born between 21 0/7 and 32 6/7 weeks gestation, and admitted to University of Iowa Health Care Neonatal Intensive Care Unit between January 2018 and December 2022. Neonates were grouped by ABO incongruent versus congruent as well as by gestational age (GA) (22-26 and 27-32 weeks GA). Demographics data were collected. Outcomes included bronchopulmonary dysplasia, pulmonary hypertension, patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC), packed red blood cell transfusions, intraventricular hemorrhage (IVH), periventricular leukomalacia, and survival to discharge. Results: ABO incongruent neonates between 27 and 32 weeks GA were more likely to have NEC and had a trend toward an increased incidence of early pulmonary hypertension. There were trends toward more heart dysfunction and severity of IVH in neonates between 22 and 26 weeks GA. Conclusion: ABO incongruency is associated with neonatal complications in the preterm population. This study is underpowered to adequately evaluate all neonatal morbidities. More studies are required to evaluate the effects of ABO incongruency on neonatal outcomes, particularly on NEC and pulmonary hypertension.
Background: Hemophilia A and B are X-linked inherited bleeding disorders resulting from factor VIII or IX deficiency and are associated with substantial morbidity beginning in early childhood. Recurrent musculoskeletal bleeding can lead to hemophilic arthropathy and long-term disability. Intracranial hemorrhage, especially in early infancy, remains a life-threatening complication with high risks of mortality and neurological sequelae. As treatment decisions in early life decisively influence lifetime outcomes, the optimal timing and mode of prophylaxis are central aspects of pediatric hemophilia care. Summary: This review summarizes the current evidence and expert opinions regarding the initiation of prophylaxis in children with hemophilia, focusing on early diagnosis, perinatal management, the timing of and indications for prophylaxis, therapeutic options, inhibitor development, and psychosocial aspects. Prophylaxis is recommended as early as possible in children with severe hemophilia and in those with moderate disease and a severe bleeding phenotype, ideally before the first joint bleed, to prevent future bleeds and microbleeds and to therefore preserve joint health. The choice of therapy (nonfactor replacement therapy, factor concentrate) should be individualized on the basis of the type and severity of hemophilia, patient age, venous access, risk of inhibitor development, clinical presentation, and family circumstances. For hemophilia A, the early use of nonfactor therapy (emicizumab) in newborns and toddlers represents an efficacious and safe therapeutic option. Data on FVIII inhibitor development in children on nonfactor prophylaxis with infrequent exposure to FVIII are still lacking. In the course of life with improved venous access, switching to FVIII prophylaxis may be beneficial in cases of bleeding despite prophylaxis with nonfactor therapy in daily life or based on parental choice. The psychosocial impact on patients and their families, especially related to treatment burden and venous access, highlights the need for shared decision-making and multidisciplinary care. Key Message: Early individualized prophylaxis is the cornerstone of modern pediatric hemophilia management. For children with hemophilia, prompt initiation after diagnosis, tailored therapeutic approaches, and close interdisciplinary support are essential for preventing life-threatening bleeding, preserving musculoskeletal and neurodevelopmental health, and ensuring a normal quality of life and participation in daily activities.
Introduction: Hemolytic disease of the fetus and newborn (HDFN), caused by the transplacental passage of maternal alloantibodies, can lead to progressive fetal organ failure and death from hydrops fetalis. Because serological tests often have limitations in predicting the clinical severity of these antibodies, in vitro assays have become promising tools, allowing the evaluation of the IgG-mediated extravascular hemolysis mechanism via macrophage Fc receptors. We aim to evaluate the monocyte monolayer assay (MMA), considered the most clinically validated tool for predicting in vivo survival in incompatible transfusion situations, as an early predictor of the severity of HDFN in sensitized pregnant women. Methods: A retrospective cohort study was conducted in sensitized pregnant women at the Hospital Italiano in Buenos Aires. The MMA was performed on all patients, dividing reactivity into four groups, G1: MMA >20%, G2: MMA between 10 and 20%, G3: MMA between 5 and 10%, and G4: MMA <5%, and the results were correlated with the degree of fetal involvement. Results: Thirty-one patients with an MMA index >20% had a significantly higher rate of serious complications, including a 100% need for intrauterine transfusion (IUT). This group also experienced six fetal deaths. In contrast, the 29 patients with an MMA index <20%, including groups 2-4, did not require IUT or postnatal transfusions. Conclusion: MMA results showed a strong correlation with the degree of fetal involvement and may be an early, highly sensitive and specific predictor of the hemolytic potential of maternal alloantibodies.
