Search Results (65)

Background: Beta-thalassemia is a hereditary hematological illness in which beta-globin chain synthesis is missing or decreased, resulting in inefficient erythropoiesis, persistent hemolysis, and anemia. It is most frequently observed in populations with a high rate of consanguineous marriages; affordability becomes a limiting factor for families with low income. Methods: In this study, we optimized Sanger sequencing of the whole HBB gene covering all three coding exons, two introns, and 5′ and 3′ UTRs. Eleven families were enrolled from Fatimid Foundation Peshawar, Khyber Pakhtunkhwa, Pakistan, with a total of 16 transfusion-dependent patients. An index patient in each family was Sanger sequenced for the HBB gene (n = 11). The variants were classified as per ACMG 2015 guidelines. Results: Sequencing analysis revealed five homozygous pathogenic variations, including three frameshifts: c.27_28dupG (p.Ser10Valfs*14), c.17_18delCT (p.Pro6Argfs17), c.126_129delCTTT (p.Phe42Leufs*19), and two splice-sites (c.92+1G>A, and c.92+5G>C) in nine families. However, two families remained unresolved. The mutation, c.27_28dupG (p.Ser10Valfs*14), was observed in several pedigrees, indicating a probable founder effect or high allele frequency within the affected population. Conclusions: The majority of detected variations in this study were classified as disease-causing, which reside in the first two coding exons and intron-1 of the HBB gene, highlighting its functional importance in the Khyber Pakhtunkhwa population. We recommend performing Sanger sequencing of exon-1-intron-1-exon-2 of the HBB gene with the optimized primers of this study. Full article

Background: β-haemoglobinopathies, including sickle cell disease and transfusion-dependent β-thalassaemia, are among the most common monogenic disorders worldwide and represent a major global health burden. Conventional treatments, such as blood transfusions, iron chelation, fetal haemoglobin induction, and allogeneic haematopoietic stem cell transplantation, have improved outcomes but remain limited by treatment-related toxicity, donor availability, and incomplete curative potential. Methods: A narrative literature review was conducted using PubMed up to 2025. Search terms included “sickle cell disease,” “sickle cell anemia,” “β-thalassemia,” “transfusion-dependent beta-thalassemia,” “gene therapy,” “gene addition,” “gene editing,” “CRISPR-Cas9,” “lentiviral vector,” “children,” “paediatric,” and “pediatric.” Relevant clinical trials, reviews, consensus statements, and guidelines were selected and qualitatively analysed. Results: Gene therapy for β-haemoglobinopathies is based mainly on two strategies: gene addition and gene editing. Gene addition uses lentiviral vectors to introduce functional or modified β-globin genes into autologous haematopoietic stem cells, whereas gene editing targets regulatory pathways, particularly BCL11A, to reactivate fetal haemoglobin synthesis or correct disease-causing mutations. Clinical studies have shown encouraging outcomes, including transfusion independence in many patients with β-thalassaemia and marked reduction or elimination of vaso-occlusive crises in sickle cell disease. Paediatric and adolescent data are increasingly promising, although still limited. Conclusions: Gene therapy is reshaping the treatment landscape of β-haemoglobinopathies by offering a personalised and potentially curative approach. However, long-term safety, conditioning toxicity, fertility preservation, accessibility, costs, and implementation in high-prevalence regions remain critical challenges. Further studies are needed to optimise patient selection and expand equitable access. Full article

Background: As survival improves in transfusion-dependent β-thalassemia, long-term adult morbidity, including cognitive dysfunction, has become increasingly relevant. Adult data remain limited, particularly in Eastern Europe, and many studies rely on single screening tools with limited control for confounding. Methods: We conducted a single-center case–control study (2024–2025) at the Congenital Hemolytic Anemia Treatment Center, University Hospital “Sv. Georgi” Plovdiv, Bulgaria. Fifty adults with transfusion-dependent β-thalassemia (86% thalassemia major; 14% transfusion-dependent intermedia) and 30 frequency-matched healthy controls completed a multi-domain cognitive battery: Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Clock Drawing Test (CDT), Trail Making Test (TMT-A/B), and timed verbal fluency. Associations between thalassemia status and cognitive outcomes were estimated using three prespecified models: unadjusted, adjusted for age and sex, and a doubly robust model combining covariate balancing propensity score inverse probability weighting (balancing BMI, smoking, education, and comorbidity) with age/sex regression adjustment. Results: Patients performed worse than controls on global cognition and executive/visuospatial measures. MoCA scores were lower in patients (−2.26 unadjusted, p = 0.016; −2.83 doubly robust, p = 0.001), as were MMSE scores (−1.64, p = 0.015; −1.87, p = 0.002). CDT performance was consistently poorer (OR ≈ 0.28–0.30 across models). Patients were slower on TMT-B (time ratio 1.35 unadjusted, p = 0.003; 1.42 doubly robust, p < 0.001); TMT-A reached significance only after weighting (ratio 1.32, p = 0.001). Verbal fluency was modestly lower with borderline significance (p ≈ 0.05–0.06). Conclusions: Transfusion-dependent β-thalassemia in adults is associated with poorer cognitive performance, particularly in global cognition and executive/visuospatial domains, with results robust across adjustment strategies. Routine multi-domain cognitive screening may be warranted in adult thalassemia care. Full article

Background/Objectives: VEXAS (Vacuoles, E1-Enzyme, X-linked, Autoinflammatory, and Somatic) syndrome is a recently described adult-onset autoinflammatory disorder. It is characterized by somatic mutations in the UBA1 gene, systemic inflammation, macrocytic anemia, cytopenias, and bone marrow vacuolization and frequently overlaps with Sweet’s syndrome, relapsing polychondritis, and myelodysplastic syndrome (MDS). Because treatment options are evolving, we reviewed the current and latest evidence of clinical features and therapeutic methods. Methods: A comprehensive literature review was conducted using PubMed and MEDLINE for studies published between 1 January 2020 and 1 July 2025. Search terms included “VEXAS” and “treatment.” Eligible publications comprised clinical trials, multicenter and observational studies, and case reports containing therapeutic data. Findings were analyzed narratively with emphasis on treatment response, steroid-sparing effects, survival outcomes, and molecular responses. Results: Glucocorticoids remain the first-line therapy for acute management; however, this comes with near-universal steroid dependence. DMARDs and TNF-α inhibitors showed limited benefits. IL-6 inhibitors and JAK inhibitors showed improvement in overall response, with JAK inhibitors demonstrating a superior effect. Ruxolitinib showed a higher complete response rate and transfusion independence compared to other JAK inhibitors. Hypomethylating agents, particularly azacitidine, improved hematologic responses in patients with co-existing MDS and reduced UBA1 variant allele burden. Allogeneic hematopoietic stem cell transplantation may be the only current curative method, though with notable transplant-related mortality. Conclusions: JAK inhibitors and hypomethylating agents offer promising disease-modifying potential, while transplant may provide curative intent in selected patients. Ongoing clinical trials are taking place to dictate the treatment direction of VEXAS syndrome. Full article

Patient Blood Management (PBM) has evolved from a transfusion-centered practice to a structured, patient-focused perioperative strategy aimed at improving surgical outcomes while preserving blood resources. In the operating room, where bleeding risk is anticipated and modifiable, PBM requires proactive intervention rather than reactive transfusion. This review synthesizes current evidence on perioperative blood conservation strategies specifically relevant to surgeons and anesthesiologists. Preoperative optimization begins with systematic identification and correction of anemia, most commonly iron deficiency, using appropriately timed oral or intravenous iron therapy and, in selected cases, erythropoiesis-stimulating agents. Careful management of anticoagulant and antiplatelet therapies, early recognition of acquired or inherited coagulopathies, and protocol-driven reversal strategies further reduce perioperative hemorrhagic risk. Intraoperatively, blood conservation depends on meticulous surgical technique, respect for anatomical planes, minimally invasive approaches, and the judicious use of advanced energy devices and topical hemostatic agents. Pharmacologic interventions—particularly tranexamic acid administered with appropriate timing and dosing—have demonstrated consistent reductions in blood loss and transfusion requirements across multiple surgical disciplines. Goal-directed coagulation management guided by viscoelastic testing allows targeted correction of specific hemostatic deficits while minimizing unnecessary blood product exposure. Acute normovolemic hemodilution and intraoperative cell salvage provide additional benefit in selected high-blood-loss procedures. Collectively, these multimodal strategies shift perioperative care from product-driven transfusion toward physiology-based blood conservation. When embedded within institutional protocols and supported by multidisciplinary collaboration, perioperative PBM reduces transfusion exposure, decreases morbidity, shortens hospital stay, and promotes sustainable stewardship of blood resources without compromising patient safety. Full article

Background/Objectives: Thalassemia and sickle cell anemia (SCA) patients require regular blood transfusions, a necessity that increases the risk of alloimmunization and complicates subsequent transfusion management. Methods: This retrospective cohort study, conducted at King Saud Medical City (KSMC) and King Fahad Medical City (KFMC) between 2018 and 2022, evaluated the frequency and risk factors of alloimmunization among 144 transfusion-dependent patients in Riyadh, Saudi Arabia. Results: By reviewing clinical and transfusion records alongside antibody screening results, the study found an overall alloimmunization prevalence of 20.1%. Notably, females exhibited a significantly higher rate (13.2%) compared to males (6.8%; p = 0.003), and younger patients (<20 years) showed a higher prevalence than older cohorts (p = 0.004). Analysis of ABO blood groups revealed that group A patients had a significantly lower alloimmunization rate (7.5%) compared to non-A patients (23.1%; p = 0.018), a finding that raises hypotheses about differential immune responsiveness but requires confirmation in larger studies. Group B showed the highest rate (35.3%), though this did not reach statistical significance after correction for multiple comparisons. RhD status was not significantly associated with alloimmunization. The most frequent alloantibodies identified were anti-E (31.3%), anti-K (12.5%), anti-D (10.4%), and anti-C (10.4%). Logistic regression further identified gender as a significant predictor (OR = 0.270; 95% CI: 0.113–0.646). Conclusions: Given that alloimmunization rates in Riyadh are moderately high—particularly among females and specific blood groups—and that the antibody profile (anti-E, anti-K, anti-C, anti-D) mirrors patterns seen in populations with recipient–donor ethnic mismatches, implementing extended blood group phenotyping for at least Rh (C, c, E, e) and Kell antigens prior to the first transfusion, and incorporating these findings into donor selection protocols, is critical to mitigating these risks. Full article

Background: Dieulafoy’s disease is a rare vascular anomaly of the gastrointestinal tract and an uncommon cause of acute upper gastrointestinal bleeding. Its occurrence during pregnancy is exceptionally rare, and the available literature is limited to isolated case reports that almost invariably describe acute and overt hemorrhagic presentations. As a result, atypical or clinically silent forms of the disease during pregnancy remain poorly characterized. Objective: To report an atypical case of Dieulafoy’s disease during pregnancy, presenting exclusively with severe progressive anemia in the absence of gastrointestinal symptoms and to contextualize this observation through a focused narrative review of the literature. Methods: An illustrative clinical case is presented, followed by a narrative review of the available literature on Dieulafoy’s disease in pregnancy. Particular attention was given to pregnancy-related physiological and hormonal adaptations, diagnostic challenges, therapeutic strategies, and reported maternal–fetal outcomes. All published cases identified in the literature were reviewed and summarized. Results: In the general population, Dieulafoy’s disease typically presents with sudden and overt gastrointestinal bleeding and is most commonly localized in the proximal stomach. In pregnancy, reported cases are rare and have almost exclusively involved acute hemorrhage occurring in the second or third trimester, frequently requiring urgent endoscopic intervention. Mechanical endoscopic hemostasis represents the treatment of choice and is generally associated with favorable maternal and fetal outcomes. In contrast, the illustrative case described herein demonstrates a clinically silent presentation, characterized by severe and progressive anemia without hematemesis, melena, or hematochezia, resulting in delayed diagnosis until upper gastrointestinal endoscopy identified multiple actively bleeding gastric Dieulafoy’s lesions. Conclusions: Dieulafoy’s disease should be considered in the differential diagnosis of severe, unexplained, or transfusion-dependent anemia during pregnancy, even in the absence of overt gastrointestinal bleeding. Pregnancy-related physiological adaptations may mask classic symptoms and complicate timely diagnosis. When clinically indicated, upper gastrointestinal endoscopy is safe and effective during pregnancy and remains central to both diagnosis and management. Increased awareness of atypical presentations may facilitate earlier recognition and improve maternal and fetal outcomes. Full article

Sickle cell disease (SCD) is the most common monogenic disorder worldwide and remains a major cause of morbidity and mortality. Sickle cell anemia (SCA), the homozygous HbSS genotype, represents the most severe and frequent form within the spectrum of SCD. Hydroxyurea (HU), a ribonucleotide reductase inhibitor, represents the first and most widely used disease-modifying therapy for SCA. This review summarizes current evidence on the mechanisms of action, clinical efficacy, systemic effects, and long-term safety of chronic HU therapy in patients with SCA. A comprehensive literature search was conducted in PubMed up to 2025 using the terms “sickle cell disease,” “sickle cell anemia”, “hydroxyurea,” and “children” or “paediatric.” Eligible studies included randomized controlled trials, cohort studies, and systematic reviews evaluating HU therapy in SCA. Literature analysis showed that HU exerts pleiotropic effects by inducing fetal hemoglobin (HbF) synthesis, improving red blood cell deformability, reducing leukocyte and platelet counts, and enhancing nitric oxide bioavailability. These mechanisms lead to decreased vaso-occlusive crises, acute chest syndrome, transfusion requirements, and overall mortality. Beyond hematologic improvement, HU confers neuroprotective benefits, modulates inflammatory and immune pathways, and supports normal growth and endocrine development in children. Adverse events, primarily mild bone marrow suppression, are dose-dependent and reversible with appropriate monitoring. No evidence supports an increased risk of malignancy with long-term use. In conclusion, chronic HU therapy is a safe, effective, and multifaceted treatment that substantially improves survival and quality of life in patients with SCA. Early initiation and individualized dosing maximize its therapeutic benefits and help prevent irreversible organ damage. Full article

Erythropoietin (EPO) is a hormone mainly produced by the kidney. EPO stimulates red blood cell production in response to hypoxia. EPO represents one of the most compelling paradoxes in medical oncology. For decades, recombinant EPO has been prescribed as an effective therapy for cancer-related anemia and fatigue, significantly improving patients’ quality of life while reducing their dependence on blood transfusions. Yet, accumulating scientific evidence knowledge has highlighted the complex interactions between EPO and tumor biology that extend well beyond its hematopoietic functions. The putative expression of EPO receptors on tumor cells has raised concerns about a potential role of EPO in promoting tumor progression, although conclusive clinical evidence remains lacking. Recent studies have revealed that EPO may contribute to immunosuppressive mechanisms within the tumor microenvironment, thereby reshaping our understanding of its risk/benefit profile in oncology. This evolving body of evidence calls for an objective reassessment of EPO’s dual nature as both a therapeutic ally and a potential oncological threat, in order to bring more caution around decision-making in the current era of strongly evolving cancer care. Full article

Background/Objectives: Colorectal cancer (CRC) is among the most commonly reported malignancies globally, taking the third place in incidence among males as well as the second among females, with over 1.9 million new cases and 935,000 deaths estimated worldwide in 2020. One of the most common and clinically significant comorbidities in patients undergoing CRC surgery is preoperative anemia, with reported prevalence ranging from 23% to over 60% depending on the population and diagnostic criteria used. The objective of the current study is to systematically evaluate the current body of evidence on preoperative anemia management in adults undergoing surgery for non-metastatic CRC. This review aims to assess the clinical impact of different iron supplementation strategies, particularly IV versus oral iron in pre-operative hematologic optimization, transfusion requirements, postoperative complications, and recovery outcomes. Methods: The current systematic review was conducted based on the PRISMA for Systematic Reviews and Meta-analysis checklist. The study has been registered to PROSPERO with the ID CRD420251113455. Results: Across all studies, IV iron and erythropoiesis-stimulating agents emerged as safe and more efficient alternatives to iron per os, especially when initiated at least two weeks before surgery. Thus, highlighting the clinical value of proactive anemia management as a cornerstone of surgical prehabilitation, potentially reducing transfusion burden and improving recovery outcomes for CRC patients. Conclusions: It is observed that IV iron therapy offers a more effective strategy than per os supplementation for correcting preoperative anemia in non-metastatic colorectal cancer patients. Their hematologic benefits enhance surgical readiness and reduce postoperative intervention needs. Thus, supporting the integration of IV iron into preoperative optimization protocols. Full article

Background: Hereditary hemorrhagic telangiectasia (HHT) is an inherited vascular bleeding disorder. The most common symptoms are recurrent, severe nosebleeds that occasionally necessitate intervention by an ENT (Ear, Nose, and Throat) specialist, as well as iron-deficiency anemia. Telangiectasia is typically located in the nasal cavity, lips, tongue, fingertips, and the gastrointestinal mucosa. Arteriovenous malformations (AVMs) are located in internal organs (brain, lungs, liver, etc.). The family history is positive for HHT. The diagnosis is based on the Curacao criteria. The endoglin and activin receptor-like kinase 1 genes (ENG and ACVRL1) are the most common mutation sites, leading to elevated endothelial growth factor (VEGF) levels. Methods: We conducted a retrospective analysis in the Department of Internal Medicine, Division of Hematology, and Center of Expertise for Rare Diseases at the University of Debrecen, spanning the period from 2010 to 2025. Records of patients referred with HHT were reviewed concerning demographic data, clinical presentations, laboratory findings, and treatment approaches. To evaluate management options, epistaxis severity was assessed using the Epistaxis Severity Score (ESS). Results: 48 HHT patients (21 male and 27 female) were included in this retrospective study. Genetic testing was positive in each case, showing mutations in the ENG (HHT1 subgroup) or ACVRL1 (HHT2 subgroup) genes. Most of the patients are followed-up with in our department. ESS was calculated at baseline and 6 months after antiangiogenic treatment by two independent physicians. Detailed computed tomography (CT) was performed in all patients. Seven patients were administered desmopressin, a synthetic analog of antidiuretic hormone (ADH), based on our previous experience in reducing bleeding in von Willebrand disease. Antiangiogenic therapy with thalidomide (50 mg oral tablets) was used in 24 patients, while bevacizumab was administered to 5 patients. Most patients experienced a remarkable decrease in epistaxis severity and a reduction in the need for transfusions (ESS before treatment: HHT1 patients, 4.15 ± 1.91 vs. ESS after treatment, 2.62 ± 0.99; HHT2 patients, 3.79 ± 3.19 vs. 2.02 ± 1.91). Subgroup analysis using paired ESS data showed a significant reduction in ESS in both HHT1 and HHT2 patients (p = 0.003 and p = 0.043, respectively). Bevacizumab further reduced the ESS, but the few cases were not suitable for statistical analysis. Serum iron levels significantly increased after antiangiogenic treatment in the HHT2 group (p = 0.01). Conclusions: HHT is a rare vascular bleeding disorder. Daily nosebleeds impair the patients’ quality of life and sometimes lead to severe transfusion-dependent iron-deficient anemia. Frequent hospitalization places a significant burden on the healthcare system. Thus, we have used treatment options for HHT patients that primarily act by inhibiting VEGF, and these treatment modalities have yielded successful results in our hands. Full article

Background: Pyruvate kinase deficiency (PKD) is the most prevalent enzymatic defect of the glycolytic pathway, causing chronic congenital non-spherocytic hemolytic anemia. Clinical severity ranges from mild anemia to transfusion-dependent diseases. Severe neonatal presentations, including liver failure, have rarely been reported. Case presentation: We report a preterm female neonate with PKD who developed early-onset hemolytic anemia, conjugated hyperbilirubinemia, hepatosplenomegaly, coagulopathy, and progressive transaminitis. Imaging demonstrated hepatomegaly with diffuse parenchymal involvement. Whole-genome sequencing identified compound heterozygous pathogenic mutations in the PKLR gene, confirming the diagnosis of PKD. The patient required continuous transfusion support and was discharged following clinical stabilization. Discussion: Although PKD most often manifests as isolated hemolytic anemia, this case illustrates a rare neonatal phenotype with concurrent liver dysfunction. We investigated the potential underlying mechanism. Recognition of hepatic involvement in PKD is essential because liver failure is associated with considerable morbidity and mortality, and it may necessitate interventions such as liver transplantation. Conclusions: This case highlights the importance of considering PKD in neonates presenting with hemolysis and liver failure. Early genetic confirmation enables timely management, including transfusion support, iron overload surveillance, and anticipatory guidance for potential hepatic complications. Full article

Background/Objectives: Thalassemias, a hereditary condition commonly linked to chronic anemia, require regular blood transfusions and repeated blood draws for assessments of hemoglobin (Hb) content, which can be uncomfortable. A promising substitute for laboratory hemoglobin testing is non-invasive spectrophotometric hemoglobin (SpHb) monitoring; however, its applicability particularly among blood transfusion-dependent thalassaemic patients needs to be investigated. This study’s primary goal was to investigate the relationships and agreements between SpHb, g/dL, and an automated hematology analyzer (Hb, g/dL) in this particular patient population. The secondary goal was to track how blood transfusions affect SpHb, g/dL, laboratory Hb, and pleth variability index (PVI, %). Methods: In this study, sixty patients were included. A Masimo Radical-7 pulse CO-oximeter was used to measure the SpHb, and a Sysmex XN-1000 hematological analyzer measured the laboratory Hb. Results: The results revealed a significant correlation between SpHb and laboratory Hb (n = 108, r = 0.587, p < 0.001) but also demonstrated that SpHb consistently overestimated laboratory Hb levels, with a mean bias of −1.18 g/dL (95% CI: −1.4344 to −0.9267). The Bland–Altman analysis showed a good degree of reliability between this bias (SpHb–Hb) and laboratory Hb (g/dL), with an Intra Class Correlation (ICC) of 0.613 but with a wide 95% CI ranging from 0.557 to 0.736 (t = 3.817, p < 0.001). The 95% limits of agreement ranged from −3.7893 to +1.4228 g/dL. Conclusions: This significant bias restricted the application of SpHb as a trustworthy method for assessing hemoglobin levels in patients with blood transfusion-dependent thalassemia. Nonetheless, the capability to monitor SpHb and PVI variations during blood transfusions offered a real-time assessment of the impact of transfusions on patients’ hemoglobin levels and volume status. Full article

Cardiac iron overload is a rare but important adverse consequence of systemic iron overload, marked by the abnormal accumulation of iron in the myocardium. It is most typically caused by hereditary hemochromatosis (mutations in the HFE gene) or secondary iron overload conditions, such as transfusion-dependent anemias. Excess iron in the myocardium causes oxidative stress, cardiomyocyte damage, and progressive fibrosis, ultimately leading to cardiomyopathy. Clinical manifestations are diverse and may include heart failure, arrhythmias, and restrictive or dilated cardiomyopathy. Given the worsened prognosis with cardiac involvement, timely diagnosis and management are essential to improve clinical outcomes. This review provides a contemporary overview of the cardiovascular complications associated with iron overload, including clinical manifestations, diagnostic approaches, and treatment options. Full article

Background/Objectives: Chronic anemia and iron overload in thalassemia lead to organ failures, including the heart, liver, endocrine glands, and spleen. Comprehensive multidisciplinary management is pivotal in improving patients’ clinical outcomes and well-being. The report aims to present a rare case of improved clinical condition in a transfusion-dependent thalassemia patient. Methods: Medical summaries were collected to compare patients’ conditions at various time frames. Furthermore, the report was composed in chronological order. Results: A 31-year-old male diagnosed with beta-thalassemia major and multiple comorbidities, including diabetes with a history of diabetic ketoacidosis, heart failure with a history of cardiac arrest, hepatomegaly, severe thoracolumbar scoliosis, and depression, exhibited a high physical endurance. The patient managed to maintain a strong treatment adherence and undergo intensive regular multidisciplinary follow-ups. The patient gained cardiac function improvement and metabolic stabilization, leading to completing a 5 k marathon without complication. Conclusions: Intensive management of iron overload through double oral chelation allows organ function improvement. Better mental health attenuates the patient’s overall well-being and is attributed to the ability to gain high physical endurance. Full article