bims-conane 2025-10-26 papers

J Investig Med High Impact Case Rep. 2025 Jan-Dec;13:13 23247096251385364

Congenital Anemia Due to Erythropoietin Gene Mutation Presenting With Diamond-Blackfan Anemia-like features.

Ibrahim AboGhayyada, Mohammad Zeidan, Dalya Abusnaina, Saja Abouodeh, Mosab Ghnimat, Mohammad Najajreh.

Diamond-Blackfan anemia (DBA) is an inherited hypoplastic anemia, caused by mutations in ribosomal protein genes. Other mutations such as mutations in the erythropoietin (EPO) gene can lead to DBA-like (DBAL) through impairment of erythropoiesis. We present a 9-year-old patient with normocytic, normochromic, transfusion-dependent anemia since birth and reticulocytopenia. Bone marrow biopsies showed erythroid hypoplasia thereby excluding myelodysplasia and iron deficiency. Whole-exome sequencing revealed a homozygous mutation (c.530G>A; p.R177Q) in the EPO gene, which encodes a protein involved in erythroid progenitor-cell proliferation, confirmed the diagnosis of the DBAL. Diagnosis of congenital anemias has been complicated by their similar characteristics with DBA, but genetic testing is important in detecting rare causes of these disorders. This diagnosis enabled us to use recombinant human EPO therapy which reduced the need for blood transfusion.

Keywords: Diamond–Blackfan anemia-like (DBAL); congenital hypoplastic anemia; erythropoietin (EPO) mutation; recombinant EPO therapy; whole-exome sequencing

DOI: https://doi.org/10.1177/23247096251385364

Blood Adv. 2025 Oct 20. pii: bloodadvances.2025017090. [Epub ahead of print]

Short- and long-term effects of transfusion in beta-thalassemia: a longitudinal study of transfusion efficiency factors.

The complex interplay between donor and recipient factors likely influences transfusion outcomes in transfusion-dependent thalassemia (TDT). We investigated physiological responses to transfusion shortly after it and one week later, focusing on Hb increment (ΔHb) and its determinants, using longitudinal data from 36 TDT subjects and 58 red blood cell (RBC) units. Immediate anemia correction post-transfusion was associated with decreases in platelets and nucleated RBCs, increases in ADAMTS13:Ag and plasma amino acid levels, and temporary rises in hemolysis and phthalates. One-week post-transfusion, at the peak of erythroid suppression, plasma antioxidants and mechanical hemolysis decreased, while proteasome activity at the RBC membrane increased. Leukocyte levels declined, markers of thrombotic risk and endothelium dysfunction improved, and hepcidin, as well as plasma glutamine and deoxyadenosine, increased. In addition to female sex and anemia, ΔHb was influenced by recipient baseline monocyte levels, hypercoagulability, and plasma metabolites, such as methionine, adenosine, acyl-carnitines, and bile acids. Donor RBC unit factors, including residual platelet levels, RBC proteasome activity, arginine metabolism, and catecholamine content also had significant correlations. Notably, the baseline neutrophil-to-lymphocyte ratio strongly affected ΔHb soon after transfusion, after adjusting for confounders. At the one-week mark, ΔHb correlated with storability markers, like oxidative hemolysis and phthalates, a first-ever described connection. Importantly, the percentage of phosphatidylserine-exposing donor RBCs and the uric acid-dependent antioxidant capacity of the RBC units significantly influenced ΔHb at the one-week timepoint. These findings enhance our understanding of transfusion dynamics, paving the way for more personalized and effective care strategies in TDT management.

DOI: https://doi.org/10.1182/bloodadvances.2025017090

Sci Rep. 2025 Oct 23. 15(1): 37142

Serum erythropoietin and its determinants and associations in patients with haemoglobin E β-thalassaemia.

Dinusha Amarasingha, Shiromi Perera, Anuja Premawardhena, Sachith Mettananda.

Erythropoietin is a hormone that stimulates erythropoiesis. The role of erythropoietin in the pathophysiology of HbE β-thalassaemia, a subtype of thalassaemia, is understudied. Here, we aim to evaluate the determinants and associations of erythropoietin in HbE β-thalassaemia patients. We conducted a cross-sectional study in Thalassaemia Centres of Colombo North Teaching Hospital, Sri Lanka, from September to December 2024. All patients with HbE β-thalassaemia were recruited. Clinical details were collected using an interviewer schedule. Haemoglobin, ferritin and erythropoietin were measured using standard laboratory methods. Serum samples of non-thalassaemia healthy volunteers were used as controls for erythropoietin measurements. Fifty-two patients (male-42.3%; mean age 24.5 ± 13.4 years) were recruited. The mean erythropoietin of HbE β-thalassaemia patients [137 (± 127) mIU/mL] was significantly higher than that of controls [21.2 (± SD16.3) mIU/mL, p < 0.001]. Among HbE β-thalassaemia patients, erythropoietin showed a gradual and significant decline with age (r = - 0.34, p < 0.05) irrespective of the haemoglobin level. Patients who underwent splenectomy had a significantly lower median erythropoietin level compared to those who did not (40 vs. 129 mIU/mL, p < 0.001). Patients with haemolysis and anaemia-related complications, especially gallstones, had significantly lower median erythropoietin level compared to those without (69.2 vs. 125.9 mIU/mL, p = 0.039). Erythropoietin response in HbE β-thalassaemia decreased gradually with age, irrespective of the degree of anaemia. Splenectomised patients had significantly lower erythropoietin levels compared to non-splenectomised patients. Lower erythropoietin level, which could be due to age-related decline or splenectomy, was positively associated with a high prevalence of haemolysis and anaemia-related complications.

Keywords: Erythropoietin; Gallstones; Haemoglobin E β-thalassaemia; Splenectomy; Thalassaemia

DOI: https://doi.org/10.1038/s41598-025-21010-9

Pediatr Cardiol. 2025 Oct 18.

Association Between G6PD Deficiency and Congenital Heart Disease Incidence and Hospital Outcomes.

Alana M Hendrickson, Natalie E Caryl, Omar Meziab, Jennifer G Andrews, Brent J Barber, Michael D Seckeler.

G6PD deficiency classically presents with hemolytic anemia, but associations have been described with atherogenesis and coronary artery disease secondary to increased oxidative stress. There are limited data that also suggest a link between G6PD deficiency and the development of congenital heart disease (CHD), possibly through the same mechanism. We hypothesize a higher incidence of CHD among individuals with G6PD deficiency as well as worse hospital outcomes for those with CHD and G6PD deficiency. We performed a retrospective review of a national administrative database from 10/2019 to 3/2024 for admissions of individuals aged 0-25 years with ICD-10 codes for moderate-to-severe CHD with and without G6PD deficiency (D55.0, D75.A). Additional data included demographics, hospital outcomes, and costs. Hospital outcomes were compared. There were 213,708 admissions with CHD and <1% had G6PD deficiency. Of the 6,363 admissions with G6PD, 289 (4.5%) had CHD and of 11,179,670 without G6PD, 213,419 (1.9%) had CHD (p < 0.001). Admissions with CHD and G6PD deficiency were predominantly Black/African American and male (consistent with G6PD deficiency epidemiology), with a longer length of stay and higher hospital costs than those without G6PD deficiency. Our findings support a higher incidence of CHD associated with G6PD deficiency as well as worse hospital outcomes for those with CHD and comorbid G6PD deficiency. More work is needed to identify a potential causative link to further understand mechanisms for CHD development.

Keywords: Congenital heart disease; G6PD deficiency; Hypoplastic left heart syndrome; Pulmonary artery stenosis; Tetralogy of fallot

DOI: https://doi.org/10.1007/s00246-025-04071-5