RARE DISEASE
Hereditary spherocytosis
Hereditary spherocytosis
Hereditary spherocytosis
Synonyms: Minkowski-Chauffard disease
Synonyms: Minkowski-Chauffard disease
Synonyms: Minkowski-Chauffard disease
Drug discovery
0
drugs
With orphan designations
Overview
Hereditary spherocytosis (HS) is an autosomal dominant* congenital hemolytic anemia caused by defects in erythrocyte membrane proteins (spectrin, ankyrin, band 3), leading to spherical RBCs with reduced deformability and splenic sequestration [1][4][13]. Clinical presentation varies from asymptomatic carriers to severe anemia with jaundice, splenomegaly, and pigment gallstones [1][10]. Diagnosis relies on spherocytes on blood smear, elevated reticulocytes, negative DAT, and osmotic fragility testing [1][8]. Management includes folate supplementation, transfusions for crises, and splenectomy for severe cases ≥6 years [5][12].
Categories: rare genetic diseases, rare hematological diseases
Research Papers
414 drug discovery papers about Hereditary spherocytosis, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
414 drug discovery papers about Hereditary spherocytosis, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-07-12 | Heparin combined with urokinase therapy for the treatment of acute portal vein thrombosis in children.
Acute portal vein thrombosis (PVT) poses a significant threat to life, with mortality rates ranging from 20% to 50%. However, a clear consensus on the management of acute PVT in children is lacking, and treatment strategies often rely on protocols established for adults. This study summarizes our experience and results in treating acute PVT with heparin combined with urokinase, providing reference data for the diagnosis and treatment of pediatric acute PVT. From November 2017 to February 2026, 5 children (2 males and 3 females) experienced acute PVT after surgery in our hospital. The ages of these children ranged from 2 to 14 years (median: 13 years). Among the 5 patients, one had hereditary spherocytosis (HS), one had total splenic infarction caused by myeloproliferative neoplasms (MPNs), and three had Abernethy malformation. Splenectomy was performed in two patients with HS and MPN, and ligation of the portosystemic shunt was performed in the other three patients with Abernethy malformation. Abdominal ultrasound (US) and enhanced computed tomography (CT) were routinely performed at postoperative days 1-7 to detect PVT. An anticoagulant and thrombolytic treatment protocol involving the combined use of heparin and urokinase is implemented in cases of PVT involving the main portal vein and/or superior mesenteric vein (SMV); in this, intravenous heparin is administered continuously at an initial dosage of 20 U/kg per hour with an increased infusion rate to achieve APTT of 60-85 s, and intravenous urokinase is continuously administered at a dosage of 4400 U/kg per hour for 2-6 h every day. After the stabilization or disappearance of the PVT, oral medications, including aspirin and dipyridamole or rivaroxaban, were used for 6 months. The routine follow-up was performed after 1, 3, and 6 months, and every 6 months thereafter. The acute PVT was detected by US and CT in all patients at postoperative days 1-7 (median: 3 days). The thrombus was located in the main portal vein in 3 patients, in the SMV in 4 patients, in the IMV in 3 patients, and in the splenic vein in 4 patients. PVT occurred simultaneously in three or more branches of the portal vein system in 4 patients. One patient experienced severe abdominal pain caused by PVT, and there were no symptoms, including abdominal pain, hematochezia, nausea, or vomiting in the other 4 patients. When portal vein thrombosis is detected, there is a notable elevation in D-dimer levels. The level of D-dimer was gradually reduced, followed by the reduction of PVT after the anti-coagulation and thrombolysis therapy. The usage of heparin combined with urokinase therapy was successful in all patients; one patient developed CTPV but exhibited no symptoms of portal hypertension, whereas the PVT completely resolved in the remaining four patients between after 19 days to 6 months. There was no bleeding caused by anticoagulation or thrombolysis during therapy. The duration of hospitalization after surgery ranged from 15 to 34 days (median: 20 days). The duration of follow-up ranged from 2 months to 4 years (median: 1 year). There was no recurrence of PVT in all patients. The use of heparin combined with urokinase for the treatment of pediatric PVT is feasible and effective under the premise of ensuring safety. Nevertheless, further verification of its safety and effectiveness is still needed through increased sample size.
2026-07-10 | Role of Next-Generation Sequencing in Deciphering Congenital Hemolytic Anemia: A Case of Multiple Mutations Leading to Dual Congenital Hemolytic Anemia
Before the widespread availability of next-generation sequencing (NGS), the diagnosis of hereditary spherocytosis (HS) and dehydrated hereditary stomatocytosis (DHS) was predominantly clinical. Here, we describe a patient with both HS and DHS who was initially treated for HS until NGS revealed that she had concomitant HS and DHS, leading to a pivot in clinical management. A 21-year-old female patient presented for evaluation of hemolytic anemia during pregnancy. The patient was clinically diagnosed with HS and treated with as-needed transfusions, with a plan for splenectomy. NGS revealed both HS and DHS. Thus, splenectomy was canceled, and aspirin was started. While treatments for HS and DHS differ greatly, in this case, where the patient has both, it is critical that treatment for DHS is prioritized because of the high risk of thromboembolic events following splenectomy. Early genetic evaluation is critical to provide an accurate diagnosis and to guide appropriate management.
2026-07-01 | Pyruvate kinase activators in the context of erythropoiesis defects
Pyruvate kinase activators are a promising class of small molecules that boost glycolytic flux and influence cellular energy metabolism. This review covers the development of pyruvate kinase activation as a therapeutic strategy, its impact on conditions such as pyruvate kinase deficiency, thalassemia, sickle cell disease, myelodysplastic syndrome, and hereditary spherocytosis. The review focuses on the role of pyruvate kinase activity dysregulation in various metabolic and hematologic disorders, the pharmacologic activators that modulate these disease-related metabolic pathways, as well as the clinical evidence supporting its application in these diseases.
2026-05-18 | Targeting pyruvate kinase in rare anemias: a novel therapeutic strategy
Red blood cells (RBCs) are responsible for oxygen transport throughout the human body, which is necessary for the cellular processes in different tissues. For proper functionality and survival of RBCs, they are dependent on glycolysis, the process that generates energy within RBCs. A key enzyme in glycolysis is pyruvate kinase (PK). The aim of this thesis was to shed light on PK in RBCs of patients with different rare (RBC) disorders. These disorders are hereditary spherocytosis (HS), hereditary xerocytosis (HX), and the myelodysplastic syndromes (MDS). HS and HX are congenital diseases of the RBC, where RBCs are broken down more rapidly in the spleen, leading to anemia. MDS are a group of acquired bone marrow diseases, occurring more frequently in late adulthood. Patients with MDS suffer from impaired production of RBCs due to bone marrow dysplasia, resulting in anemia. We observe that in all three of these diseases, the enzyme PK is affected in the RBCs. Therefore, we investigated the ex vivo effects of PK activators on the RBCs of these patients. Our results show that the RBCs of all three patient groups respond to PK activation. PK activity increases, resulting in increased energy levels. This also has a beneficial effect on the functionality of the RBCs. This forms the basis for future research into whether these patients may also benefit from taking PK activators as therapeutic drugs. Additionally, the role of a diagnostic test, namely osmotic gradient ektacytometry, is further explored: this laboratory test may also be of value for understanding the disease mechanism and assessing the disease severity in patients with HS. This is important, as it may allow physicians to extract even more information from a standard diagnostic test.
2026-01-28 | Hereditary Spherocytosis: Linking Ion Transport Defects to Osmotic Gradient Ektacytometry Profiles-A Review.
Hereditary spherocytosis (HS) is the most common inherited red blood cell (RBC) membrane disorder and has traditionally been attributed to defects in cytoskeletal proteins such as spectrin, ankyrin, band 3, and protein 4.2. Growing evidence, however, shows that disturbances in ion transport also contribute to HS pathophysiology. This review summarizes current understanding of HS by integrating membrane structural defects with abnormalities in ion homeostasis and highlights the diagnostic value of osmotic gradient ektacytometry (OGE). Beyond membrane instability, HS erythrocytes exhibit increased cation permeability with abnormal Na+ influx and K+ loss, leading to cellular dehydration, elevated mean corpuscular hemoglobin concentration (MCHC), and reduced deformability. Dysregulation of mechanosensitive and Ca2+-activated K+ channels (PIEZO1, KCNN4) may modulate disease expression. OGE-now the reference functional test for RBC deformability-identifies reproducible phenotypes reflecting hydration status, including dehydrated (HS1) and partially hydrated (HS2) HS profiles. When combined with next-generation sequencing (NGS), OGE improves differentiation between HS and overlapping membranopathies such as hereditary xerocytosis or stomatocytosis. In conclusion, HS is a multifactorial disorder resulting from the interplay between cytoskeletal fragility, oxidative stress, and dysregulated ion transport. Integrated diagnostic strategies that combine hematologic indices, OGE, and targeted NGS enhance diagnostic accuracy, support genotype-phenotype interpretation, and guide individualized clinical management. Future efforts should focus on ion-channel modulation and wider adoption of functional assays in precision hematology.
cell therapies
2024-03-20 | Artificial cells for in vivo biomedical applications through red blood cell biomimicry
Abstract Recent research in artificial cell production holds promise for the development of delivery agents with therapeutic effects akin to real cells. To succeed in these applications, these systems need to survive the circulatory conditions. In this review we present strategies that, inspired by the endurance of red blood cells, have enhanced the viability of large, cell-like vehicles for in vivo therapeutic use, particularly focusing on giant unilamellar vesicles. Insights from red blood cells can guide modifications that could transform these platforms into advanced drug delivery vehicles, showcasing biomimicry’s potential in shaping the future of therapeutic applications.
2021-07-07 | Case Report: Signal Transducer and Activator of Transcription 3 Gain-of-Function and Spectrin Deficiency: A Life-Threatening Case of Severe Hemolytic Anemia.
STAT3 gain-of-function (GOF) mutations can be responsible for an incomplete phenotype mainly characterized by hematological autoimmunity, even in the absence of other organ autoimmunity, growth impairment, or severe infections. We hereby report a case with an incomplete form of STAT3 GOF intensified by a concomitant hereditary hematological disease, which misleads the diagnosis. The patient presented with lymphadenopathy, splenomegaly, hypogammaglobulinemia, and severe autoimmune hemolytic anemia (AIHA) with critical complications, including stroke. A Primary Immune Regulatory Disorders (PIRD) was suspected, and molecular analysis revealed a de novo STAT3 gain-of-function mutation. The response to multiple immune suppressive treatments was ineffective, and further investigations revealed a spectrin deficiency. Ultimately, hematopoietic stem cell transplantation from a matched unrelated donor was able to cure the patient. Our case shows an atypical presentation of STAT3 GOF associated with hereditary spherocytosis, and how achievement of a good long-term outcome depends on a strict clinical and laboratory monitoring, as well as on prompt therapeutic intervention.
2016-10-06 | Erythrocytes as Carriers for Drug Delivery in Blood Transfusion and Beyond
Red blood cells (RBCs) are innate carriers that can also be engineered to improve the pharmacokinetics and pharmacodynamics of many drugs, particularly biotherapeutics. Successful loading of drugs, both internally and on the external surface of RBCs, has been demonstrated for many drugs including anti-inflammatory, antimicrobial, and antithrombotic agents. Methods for internal loading of drugs within RBCs are now entering clinical use. Although internal loading can result in membrane disruption that may compromise biocompatibility, surface loading using either affinity or chemical ligands offers a diverse set of approaches for the production of RBC drug carriers. A wide range of surface determinants is potentially available for this approach, although there remains a need to characterize the effects of coupling agents to these surface proteins. Somewhat surprisingly, recent data also suggest that red cell-mediated delivery may confer tolerogenic immune effects. Questions remaining before widespread application of these technologies include determining the optimal loading protocol, source of RBCs, and production logistics, as well as addressing regulatory hurdles. Red blood cell drug carriers, after many decades of progress, are now poised to enter the clinic and broaden the potential application of RBCs in blood transfusion.
2006-07-12 | Iron overload and prolonged ingestion of iron supplements: Clinical features and mutation analysis of hemochromatosis‐associated genes in four cases
Abstract We evaluated and treated four white adults (one man, three women) who had iron overload associated with daily ingestion of iron supplements for 7, 15, 35, and 61 years, respectively. We performed HFE mutation analysis to detect C282Y, H63D, and S65C in each patient; in two patients, HFE exons were sequenced. In two patients, direct sequencing was performed to detect coding region mutations of TFR 2 , HAMP , FPN 1 , HJV , and ALAS 2 . Patients 1–4 ingested ˜153, 547, 1,341, and 4,898 g of inorganic iron as supplements. Patient 1 had hemochromatosis, HFE C282Y homozygosity, and β‐thalassemia minor. Patient 2 had spherocytosis and no HFE coding region mutations. Patient 3 had no anemia, a normal HFE genotype, and no coding region mutations in HAMP , FPN 1 , HJV , or ALAS 2 ; she was heterozygous for the TFR 2 coding region mutation V583I (nt 1,747 G→A, exon 15). Patient 4 had no anemia and no coding region mutations in HFE , TFR 2 , HAMP , FPN 1 , HJV , or ALAS 2. Iron removed by phlebotomy was 32.4, 10.4, 15.2, and 4.0 g, respectively. There was a positive correlation of log 10 serum ferritin and the quantity of iron removed by phlebotomy ( P = 0.0371). Estimated absorption of iron from supplements in patients 1–4 was 20.9%, 1.9%, 1.1%, and 0.08%. We conclude that the clinical phenotypes and hemochromatosis genotypes of adults who develop iron overload after ingesting iron supplements over long periods are heterogeneous. Therapeutic phlebotomy is feasible and effective, and would prevent complications of iron overload. Am. J. Hematol., 2006. © 2006 Wiley‐Liss, Inc.
2003-04-01 | Allogeneic bone marrow transplantation for severe post‐splenectomy thrombophilic state in leaky red cell membrane haemolytic anaemia of the stomatocytosis class
Summary. The tendency for thrombosis to occur if haemolysis persists after splenectomy is especially marked in ‘hereditary stomatocytosis’, in which the red cell membrane ‘leaks’ Na and K. A 21‐year‐old woman, who was splenectomized in childhood for a congenital haemolytic state, presented with major pulmonary embolism that recurred despite anticoagulation. Tests showed a significant cation leak with a ‘shallow‐slope’ abnormality in temperature dependence. Allogeneic bone marrow transplantation caused the thrombophilic state to cease and subsequently anticoagulation was stopped without recurrence of thromboembolism. However, she died 9 months after transplantation: iron overload, intensified by the transfusion demands of the transplant, was a major factor.
proteins
2024-10-25 | Biomechanics of phagocytosis of red blood cells by macrophages in the human spleen.
The clearance of senescent and altered red blood cells (RBCs) in the red pulp of the human spleen involves sequential processes of prefiltration, filtration, and postfiltration. While prior work has elucidated the mechanisms underlying the first two processes, biomechanical processes driving the postfiltration phagocytosis of RBCs retained at interendothelial slits (IES) are still poorly understood. We present here a unique computational model of macrophages to study the role of cell biomechanics in modulating the kinetics of phagocytosis of aged and diseased RBCs retained in the spleen. After validating the macrophage model using in vitro phagocytosis experiments, we employ it to probe the mechanisms underlying the kinetics of phagocytosis of mechanically altered RBCs, such as heated RBCs and abnormal RBCs in hereditary spherocytosis (HS) and sickle cell disease (SCD). Our simulations show pronounced deformation of the flexible and healthy RBCs in contrast to minimal shape changes in altered RBCs. Simulations also show that less deformable RBCs are engulfed faster and at lower adhesive strength than flexible RBCs, consistent with our experimental measurements. This efficient sensing and engulfment by macrophages of stiff RBCs retained at IES are expected to temper splenic congestion, a common pathogenic process in malaria, HS, and SCD. Altogether, our combined computational and in vitro experimental studies suggest that mechanical alterations of retained RBCs may suffice to enhance their phagocytosis, thereby adapting the kinetics of their elimination to the kinetics of their mechanical retention, an equilibrium essential for adequately cleaning the splenic filter to preserve its function.
2021-09-28 | Tangential flow filtration of haptoglobin.
Haptoglobin (Hp) is a plasma glycoprotein that scavenges cell-free hemoglobin (Hb). Hp has various potential therapeutic applications, but it has been mainly studied for treatment of acute hemolytic conditions that can arise from situations such as massive blood transfusion, infusion of stored red blood cells, severe burns, trauma, sepsis, radiation injury, and others. Therefore, Hp may also be beneficial during chronic hemolytic disease states such as hereditary spherocytosis, nocturnal hemoglobinuria, sickle-cell anemia, and malaria. Various methods have been developed to purify Hp from plasma or plasma fractions. However, none of these methods have exploited the large molecular weight (MW) range distribution of Hp polymers to easily isolate Hp from other plasma proteins. The present study used tangential flow filtration (TFF) to isolate polymeric Hp from plasma proteins using human Fraction IV (FIV) as the starting material. After removal of insoluble material from a suspension of FIV paste, the protein mixture was clarified on a 0.2 μm hollow fiber (HF) TFF filter. The clarified protein solution was then bracketed based on protein MW using HF filters with MW cut-offs (MWCOs) of 750, 500, and 100 kDa. Using untreated FIV, the Hp purity of the main bracket was ~75% with a total Hb binding capacity (HbBC) yield of 1.2 g starting from 500 g of FIV paste. However, pretreatment of FIV with fumed silica to remove lipoproteins increased Hp purity to >95% with a HbBC yield of 1.7 g per 500 g of FIV. Taken together this study provides a novel and scalable method to purify Hp from plasma or plasma fractions.
2021-04-06 | Successful Splenectomy Management in a Patient With Moderate Factor VII Deficiency and Concomitant Severe Hereditary Spherocytosis.
By the advent of the effective therapies for many coagulation diseases and hereditary spherocytosis (HS), patient's survival has been improved significantly; however, if patients are diagnosed late or left untreated, both diseases could ominously be life threatening. Concurrent occurring of factor VII (FVII) deficiency and HS is extremely rare and there is no literature report that explain this condition, thus far. In this study, we confronted a 9-year-old female patient diagnosed with HS and enlarged spleen as a result of this blood disorder. Given to her sever signs and symptoms of splenomegaly, she was candidate for emergent splenectomy. However, assessment of coagulation tests revealed a prolonged prothrombin time, suggesting the moderate FVII deficiency. With a multidisciplinary consultation, we decided to performed total splenectomy with prophylaxis administration of totally 6 doses of active recombinant FVII, initiated 1 hour before surgery and followed until 30 hours postoperation. As a result of cautious undertaken in Mofid Children's Hospital, the patient did not experience any hemostatic defect. Patient is now 14-year-old, generally well-being under regular surveillance of FVII deficiency.
2020-03-01 | Linkage of typically cytosolic peroxidases to erythrocyte membrane – A possible mechanism of protection in Hereditary Spherocytosis
Hereditary Spherocytosis (HS) is a non-immune hemolytic anemia associated to oxidative stress (OS), namely to the linkage of cytosolic antioxidant enzymes to the erythrocyte membrane.Our aims were to evaluate erythrocyte OS changes and the membrane linkage of peroxiredoxin 2 (Prx2), glutathione peroxidase (GPx) and catalase (CAT) in unsplenectomized (unspl) and splenectomized (spl) HS patients and to search for associations with clinical severity (in unspl HS patients).We studied 114 HS patients (74 unspl and 40 spl) and 30 healthy individuals and we evaluated membrane bound hemoglobin (MBH), membrane lipid-peroxidation (LPO), enzymatic activities of GPx and CAT and the amounts of membrane bound Prx2, GPx and CAT, as well as, clinical and analytical parameters for characterization of HS.We found that unspl HS patients showed clear signs of anemia and in spl HS, a correction to this anemia was observed; the latter patients presented higher levels of OS biomarkers, namely, MBH and LPO.CAT was detected in the membrane of all individuals (control and HS groups), while GPx and Prx2 were only present in HS patients; moreover, their linkage to the membrane (in HS) appears to be cumulative since membrane bound peroxidases amount was higher as the number of peroxidases detected increased.MBH increased with the number/amount of membrane bound peroxidases, however LPO levels remained similar.In conclusion, our data suggest that the binding of these typically cytosolic peroxidases to erythrocyte membrane may be part of a mechanism of membrane protection to maintain its integrity by possibly regulating LPO.
2019-09-10 | Treatment of a Child With Submassive Pulmonary Embolism Associated With Hereditary Spherocytosis Using Ultrasound-Assisted Catheter-Directed Thrombolysis
Background: The clinical presentation of hereditary spherocytosis varies from no symptoms to severe hemolytic anemia requiring splenectomy. Splenectomy imposes the risk of hypercoagulability and acute pulmonary embolism. Catheter-directed thrombolysis is an established treatment for submassive pulmonary embolism in adults. However, the literature regarding its use in children is limited. Case Report: We present the case of a 12-year-old male with hereditary spherocytosis who was diagnosed with pulmonary embolism and successfully treated with catheter-directed thrombolysis. The patient was initially treated with 10.5 mg of recombinant tissue plasminogen activator (r-tPA) delivered over 8 hours. However, because of minimal clinical and hemodynamic improvement, a second course of thrombolytic was administered for an additional 24 hours (25 mg of r-tPA), and the treatment resulted in marked clinical and hemodynamic improvement. Clot resolution was confirmed via angiography. The patient was discharged on enoxaparin and with regular follow-up. One year later, the patient was asymptomatic on enoxaparin. Conclusion: This case demonstrates that catheter-based treatment of submassive pulmonary embolism restores hemodynamic stability and thus is an alternative to surgery or systemic thrombolysis, even in the pediatric setting. While catheter-directed thrombolysis is a safe and effective alternative to systemic thrombolysis, further research is needed to establish appropriate dosing and indications in the adolescent population.
gene therapies
2026-07-23 | Hereditary Spherocytosis in a Child due to a Deletion in β‐Spectrin Detected by Low‐Input DNA Long‐Read Whole‐Genome Sequencing
The authors declare no conflicts of interest. Relevant data are available from the corresponding author upon reasonable request. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
2026-03-19 | Symptomatic Recurrent Splenomegaly Following Partial Splenectomy in Patients With Hereditary Spherocytosis.
Hereditary spherocytosis (HS) is an inherited hematologic disorder characterized by spherical erythrocytes that are prematurely destroyed in the spleen. Total splenectomy (TS) and partial splenectomy (PS) are surgical interventions used to manage HS, but long-term outcomes, including recurrence of splenomegaly and splenomegaly-related symptoms, remain poorly understood. This study aims to evaluate the long-term recurrence of splenomegaly and splenomegaly-related symptoms in children with HS who underwent PS versus TS at a single institution between 2008 and 2020. A retrospective chart review of children with HS who underwent TS or PS was performed. The primary end point was the long-term recurrence of splenomegaly and splenomegaly-related symptoms. Variables collected included age, sex, surgical method (PS vs. TS), postoperative hematologic markers, splenic volume, postoperative complications, length of hospital stay, recurrence of splenomegaly, and need for completion splenectomy. Symptomatic recurrent splenomegaly is defined as splenic volume > 450 mL and the presence of symptoms directly attributable to the spleen and its effects on adjacent organs or hemolysis. Statistical analysis included comparisons of continuous variables using a Kruskal-Wallis test and categorical variables using a Fisher's exact test. Forty-four patients with HS met the inclusion criteria for the study. Of these, 31 (71%) patients underwent laparoscopic PS and 13 (30%) patients underwent laparoscopic TS. TS was associated with significantly less intraoperative blood loss (p = 0.003), shorter hospital stays (p = 0.01), and greater reduction in hemolysis compared to PS, as evidenced by lower postoperative bilirubin levels and reticulocyte counts (both p < 0.001). Eighteen (58%) PS patients experienced recurrent splenomegaly, and six (19%) PS patients experienced splenomegaly-related symptoms leading to completion splenectomy. Among the six patients who required completion splenectomy, intraoperative hemorrhage requiring conversion to open procedure occurred in half. The median time to need completion splenectomy was 10.5 years (range, 3-15 years). TS offers more significant long-term hematologic improvements but comes with the loss of immune function and increased risk of overwhelming post-splenectomy infection (OPSI). PS, while preserving some splenic function and theoretically reducing OPSI risk, carries a higher risk of recurrent symptomatic splenomegaly and may require additional surgeries. These findings highlight the importance of long-term follow-up for HS patients who undergo PS and the need to balance the advantages and risks of both surgical approaches.
2026-03-05 | A novel variant of the erythrocyte spectrin-beta gene (SPTB) causing hereditary spherocytosis in a Sri Lankan child
No abstract available
2026-02-13 | Frequency and characterization of Parvovirus B19 infections in children with hematologic diseases: a single-center retrospective analysis
Introduction: Parvovirus B19 (PVB19) represents a clinically relevant pathogen in individuals with hematologic disorders. While infection may remain clinically silent, it can also precipitate significant hematologic complications, including severe anemia or aplastic crisis. This study aimed to evaluate the prevalence of PVB19 infection in pediatric patients hospitalized for hematologic diseases and to delineate the clinical profile of active infections. Material and methods: The cohort consisted of 103 children admitted to the Department of Pediatric Hematology, Oncology, and Transplantology at the Children’s University Hospital in Lublin between 2023 and 2025. Serological testing for IgM and IgG antibodies against PVB19 was performed using enzyme-linked immunosorbent assay (ELISA). Patients were stratified into two groups: those with active infection, defined as IgM ≥ 1.1, and those with negative IgM titers. Analyses included demographic characteristics, laboratory indices, hospitalization duration, transfusion requirements, and infection-related complications. Results: IgM seropositivity was identified in 13 patients (12.6%). The most frequent underlying hematologic disorder was hereditary spherocytosis (n = 3). Hospitalization ranged from 1 to 113 days. Eight patients required red blood cell transfusions. The most frequent clinical features included fever (n = 6) and upper respiratory tract infection (n = 3). Statistical analysis revealed differences in infection prevalence across age categories (P = 0.02), with the highest incidence in the 4–6-year age group (n = 7). Conclusions: The clinical spectrum of PVB19 infection varied from mild disease to severe hematologic complications. No correlation between sex and susceptibility to PVB19 infection was observed. The results suggest a predominance of infections in early childhood; however, confirmation requires validation in larger study cohorts.
2026-01-01 | Decoding hereditary spherocytosis: Unveiling the genes as a potential causative agent
Hereditary spherocytosis (HS) is the most common inherited hemolytic anemia in populations of northern European descent, arising from mutations in genes encoding key erythrocyte membrane proteins, including ANK1 , SPTB , SLC4A1 , SPTA1 , and EPB42 . These genetic defects disrupt the vertical linkages between the red blood cell (RBC) plasma membrane and its underlying cytoskeleton, reducing RBC deformability and leading to characteristic spherocytosis, premature hemolysis, and accelerated splenic clearance. Inheritance is predominantly autosomal dominant, although autosomal recessive forms occur, particularly involving SPTA1 and EPB42. Clinically, HS manifests with anemia, jaundice, splenomegaly, and complications such as cholelithiasis. This study aimed to identify and characterize pathogenic variants in primary HS genes, establish genotype–phenotype correlations, and enhance diagnostic accuracy to guide personalized management within a defined cohort. Diagnostic advancements, notably the tests of next-generation sequencing and the eosin-5-maleimide binding test, have improved the detection of genetic heterogeneity, yet regional underdiagnosis persists. A comprehensive understanding of the HS genetic spectrum is therefore critical not only for precise diagnosis and optimized patient care but also for informing the development of future gene-targeted therapies, including CRISPR-based approaches. Regional epidemiological investigations, including limited data from Iraq, suggest that HS remains underdiagnosed despite its significant clinical impact. A comprehensive understanding of the HS genetic spectrum is imperative for accurate diagnosis, optimized personalized management, and the eventual development of gene-based therapeutic interventions.
small molecules
2026-07-12 | Heparin combined with urokinase therapy for the treatment of acute portal vein thrombosis in children.
Acute portal vein thrombosis (PVT) poses a significant threat to life, with mortality rates ranging from 20% to 50%. However, a clear consensus on the management of acute PVT in children is lacking, and treatment strategies often rely on protocols established for adults. This study summarizes our experience and results in treating acute PVT with heparin combined with urokinase, providing reference data for the diagnosis and treatment of pediatric acute PVT. From November 2017 to February 2026, 5 children (2 males and 3 females) experienced acute PVT after surgery in our hospital. The ages of these children ranged from 2 to 14 years (median: 13 years). Among the 5 patients, one had hereditary spherocytosis (HS), one had total splenic infarction caused by myeloproliferative neoplasms (MPNs), and three had Abernethy malformation. Splenectomy was performed in two patients with HS and MPN, and ligation of the portosystemic shunt was performed in the other three patients with Abernethy malformation. Abdominal ultrasound (US) and enhanced computed tomography (CT) were routinely performed at postoperative days 1-7 to detect PVT. An anticoagulant and thrombolytic treatment protocol involving the combined use of heparin and urokinase is implemented in cases of PVT involving the main portal vein and/or superior mesenteric vein (SMV); in this, intravenous heparin is administered continuously at an initial dosage of 20 U/kg per hour with an increased infusion rate to achieve APTT of 60-85 s, and intravenous urokinase is continuously administered at a dosage of 4400 U/kg per hour for 2-6 h every day. After the stabilization or disappearance of the PVT, oral medications, including aspirin and dipyridamole or rivaroxaban, were used for 6 months. The routine follow-up was performed after 1, 3, and 6 months, and every 6 months thereafter. The acute PVT was detected by US and CT in all patients at postoperative days 1-7 (median: 3 days). The thrombus was located in the main portal vein in 3 patients, in the SMV in 4 patients, in the IMV in 3 patients, and in the splenic vein in 4 patients. PVT occurred simultaneously in three or more branches of the portal vein system in 4 patients. One patient experienced severe abdominal pain caused by PVT, and there were no symptoms, including abdominal pain, hematochezia, nausea, or vomiting in the other 4 patients. When portal vein thrombosis is detected, there is a notable elevation in D-dimer levels. The level of D-dimer was gradually reduced, followed by the reduction of PVT after the anti-coagulation and thrombolysis therapy. The usage of heparin combined with urokinase therapy was successful in all patients; one patient developed CTPV but exhibited no symptoms of portal hypertension, whereas the PVT completely resolved in the remaining four patients between after 19 days to 6 months. There was no bleeding caused by anticoagulation or thrombolysis during therapy. The duration of hospitalization after surgery ranged from 15 to 34 days (median: 20 days). The duration of follow-up ranged from 2 months to 4 years (median: 1 year). There was no recurrence of PVT in all patients. The use of heparin combined with urokinase for the treatment of pediatric PVT is feasible and effective under the premise of ensuring safety. Nevertheless, further verification of its safety and effectiveness is still needed through increased sample size.
2026-07-10 | Role of Next-Generation Sequencing in Deciphering Congenital Hemolytic Anemia: A Case of Multiple Mutations Leading to Dual Congenital Hemolytic Anemia
Before the widespread availability of next-generation sequencing (NGS), the diagnosis of hereditary spherocytosis (HS) and dehydrated hereditary stomatocytosis (DHS) was predominantly clinical. Here, we describe a patient with both HS and DHS who was initially treated for HS until NGS revealed that she had concomitant HS and DHS, leading to a pivot in clinical management. A 21-year-old female patient presented for evaluation of hemolytic anemia during pregnancy. The patient was clinically diagnosed with HS and treated with as-needed transfusions, with a plan for splenectomy. NGS revealed both HS and DHS. Thus, splenectomy was canceled, and aspirin was started. While treatments for HS and DHS differ greatly, in this case, where the patient has both, it is critical that treatment for DHS is prioritized because of the high risk of thromboembolic events following splenectomy. Early genetic evaluation is critical to provide an accurate diagnosis and to guide appropriate management.
2026-07-01 | Pyruvate kinase activators in the context of erythropoiesis defects
Pyruvate kinase activators are a promising class of small molecules that boost glycolytic flux and influence cellular energy metabolism. This review covers the development of pyruvate kinase activation as a therapeutic strategy, its impact on conditions such as pyruvate kinase deficiency, thalassemia, sickle cell disease, myelodysplastic syndrome, and hereditary spherocytosis. The review focuses on the role of pyruvate kinase activity dysregulation in various metabolic and hematologic disorders, the pharmacologic activators that modulate these disease-related metabolic pathways, as well as the clinical evidence supporting its application in these diseases.
2026-05-18 | Targeting pyruvate kinase in rare anemias: a novel therapeutic strategy
Red blood cells (RBCs) are responsible for oxygen transport throughout the human body, which is necessary for the cellular processes in different tissues. For proper functionality and survival of RBCs, they are dependent on glycolysis, the process that generates energy within RBCs. A key enzyme in glycolysis is pyruvate kinase (PK). The aim of this thesis was to shed light on PK in RBCs of patients with different rare (RBC) disorders. These disorders are hereditary spherocytosis (HS), hereditary xerocytosis (HX), and the myelodysplastic syndromes (MDS). HS and HX are congenital diseases of the RBC, where RBCs are broken down more rapidly in the spleen, leading to anemia. MDS are a group of acquired bone marrow diseases, occurring more frequently in late adulthood. Patients with MDS suffer from impaired production of RBCs due to bone marrow dysplasia, resulting in anemia. We observe that in all three of these diseases, the enzyme PK is affected in the RBCs. Therefore, we investigated the ex vivo effects of PK activators on the RBCs of these patients. Our results show that the RBCs of all three patient groups respond to PK activation. PK activity increases, resulting in increased energy levels. This also has a beneficial effect on the functionality of the RBCs. This forms the basis for future research into whether these patients may also benefit from taking PK activators as therapeutic drugs. Additionally, the role of a diagnostic test, namely osmotic gradient ektacytometry, is further explored: this laboratory test may also be of value for understanding the disease mechanism and assessing the disease severity in patients with HS. This is important, as it may allow physicians to extract even more information from a standard diagnostic test.
2026-01-28 | Hereditary Spherocytosis: Linking Ion Transport Defects to Osmotic Gradient Ektacytometry Profiles-A Review.
Hereditary spherocytosis (HS) is the most common inherited red blood cell (RBC) membrane disorder and has traditionally been attributed to defects in cytoskeletal proteins such as spectrin, ankyrin, band 3, and protein 4.2. Growing evidence, however, shows that disturbances in ion transport also contribute to HS pathophysiology. This review summarizes current understanding of HS by integrating membrane structural defects with abnormalities in ion homeostasis and highlights the diagnostic value of osmotic gradient ektacytometry (OGE). Beyond membrane instability, HS erythrocytes exhibit increased cation permeability with abnormal Na+ influx and K+ loss, leading to cellular dehydration, elevated mean corpuscular hemoglobin concentration (MCHC), and reduced deformability. Dysregulation of mechanosensitive and Ca2+-activated K+ channels (PIEZO1, KCNN4) may modulate disease expression. OGE-now the reference functional test for RBC deformability-identifies reproducible phenotypes reflecting hydration status, including dehydrated (HS1) and partially hydrated (HS2) HS profiles. When combined with next-generation sequencing (NGS), OGE improves differentiation between HS and overlapping membranopathies such as hereditary xerocytosis or stomatocytosis. In conclusion, HS is a multifactorial disorder resulting from the interplay between cytoskeletal fragility, oxidative stress, and dysregulated ion transport. Integrated diagnostic strategies that combine hematologic indices, OGE, and targeted NGS enhance diagnostic accuracy, support genotype-phenotype interpretation, and guide individualized clinical management. Future efforts should focus on ion-channel modulation and wider adoption of functional assays in precision hematology.
cell therapies
2024-03-20 | Artificial cells for in vivo biomedical applications through red blood cell biomimicry
Abstract Recent research in artificial cell production holds promise for the development of delivery agents with therapeutic effects akin to real cells. To succeed in these applications, these systems need to survive the circulatory conditions. In this review we present strategies that, inspired by the endurance of red blood cells, have enhanced the viability of large, cell-like vehicles for in vivo therapeutic use, particularly focusing on giant unilamellar vesicles. Insights from red blood cells can guide modifications that could transform these platforms into advanced drug delivery vehicles, showcasing biomimicry’s potential in shaping the future of therapeutic applications.
2021-07-07 | Case Report: Signal Transducer and Activator of Transcription 3 Gain-of-Function and Spectrin Deficiency: A Life-Threatening Case of Severe Hemolytic Anemia.
STAT3 gain-of-function (GOF) mutations can be responsible for an incomplete phenotype mainly characterized by hematological autoimmunity, even in the absence of other organ autoimmunity, growth impairment, or severe infections. We hereby report a case with an incomplete form of STAT3 GOF intensified by a concomitant hereditary hematological disease, which misleads the diagnosis. The patient presented with lymphadenopathy, splenomegaly, hypogammaglobulinemia, and severe autoimmune hemolytic anemia (AIHA) with critical complications, including stroke. A Primary Immune Regulatory Disorders (PIRD) was suspected, and molecular analysis revealed a de novo STAT3 gain-of-function mutation. The response to multiple immune suppressive treatments was ineffective, and further investigations revealed a spectrin deficiency. Ultimately, hematopoietic stem cell transplantation from a matched unrelated donor was able to cure the patient. Our case shows an atypical presentation of STAT3 GOF associated with hereditary spherocytosis, and how achievement of a good long-term outcome depends on a strict clinical and laboratory monitoring, as well as on prompt therapeutic intervention.
2016-10-06 | Erythrocytes as Carriers for Drug Delivery in Blood Transfusion and Beyond
Red blood cells (RBCs) are innate carriers that can also be engineered to improve the pharmacokinetics and pharmacodynamics of many drugs, particularly biotherapeutics. Successful loading of drugs, both internally and on the external surface of RBCs, has been demonstrated for many drugs including anti-inflammatory, antimicrobial, and antithrombotic agents. Methods for internal loading of drugs within RBCs are now entering clinical use. Although internal loading can result in membrane disruption that may compromise biocompatibility, surface loading using either affinity or chemical ligands offers a diverse set of approaches for the production of RBC drug carriers. A wide range of surface determinants is potentially available for this approach, although there remains a need to characterize the effects of coupling agents to these surface proteins. Somewhat surprisingly, recent data also suggest that red cell-mediated delivery may confer tolerogenic immune effects. Questions remaining before widespread application of these technologies include determining the optimal loading protocol, source of RBCs, and production logistics, as well as addressing regulatory hurdles. Red blood cell drug carriers, after many decades of progress, are now poised to enter the clinic and broaden the potential application of RBCs in blood transfusion.
2006-07-12 | Iron overload and prolonged ingestion of iron supplements: Clinical features and mutation analysis of hemochromatosis‐associated genes in four cases
Abstract We evaluated and treated four white adults (one man, three women) who had iron overload associated with daily ingestion of iron supplements for 7, 15, 35, and 61 years, respectively. We performed HFE mutation analysis to detect C282Y, H63D, and S65C in each patient; in two patients, HFE exons were sequenced. In two patients, direct sequencing was performed to detect coding region mutations of TFR 2 , HAMP , FPN 1 , HJV , and ALAS 2 . Patients 1–4 ingested ˜153, 547, 1,341, and 4,898 g of inorganic iron as supplements. Patient 1 had hemochromatosis, HFE C282Y homozygosity, and β‐thalassemia minor. Patient 2 had spherocytosis and no HFE coding region mutations. Patient 3 had no anemia, a normal HFE genotype, and no coding region mutations in HAMP , FPN 1 , HJV , or ALAS 2 ; she was heterozygous for the TFR 2 coding region mutation V583I (nt 1,747 G→A, exon 15). Patient 4 had no anemia and no coding region mutations in HFE , TFR 2 , HAMP , FPN 1 , HJV , or ALAS 2. Iron removed by phlebotomy was 32.4, 10.4, 15.2, and 4.0 g, respectively. There was a positive correlation of log 10 serum ferritin and the quantity of iron removed by phlebotomy ( P = 0.0371). Estimated absorption of iron from supplements in patients 1–4 was 20.9%, 1.9%, 1.1%, and 0.08%. We conclude that the clinical phenotypes and hemochromatosis genotypes of adults who develop iron overload after ingesting iron supplements over long periods are heterogeneous. Therapeutic phlebotomy is feasible and effective, and would prevent complications of iron overload. Am. J. Hematol., 2006. © 2006 Wiley‐Liss, Inc.
2003-04-01 | Allogeneic bone marrow transplantation for severe post‐splenectomy thrombophilic state in leaky red cell membrane haemolytic anaemia of the stomatocytosis class
Summary. The tendency for thrombosis to occur if haemolysis persists after splenectomy is especially marked in ‘hereditary stomatocytosis’, in which the red cell membrane ‘leaks’ Na and K. A 21‐year‐old woman, who was splenectomized in childhood for a congenital haemolytic state, presented with major pulmonary embolism that recurred despite anticoagulation. Tests showed a significant cation leak with a ‘shallow‐slope’ abnormality in temperature dependence. Allogeneic bone marrow transplantation caused the thrombophilic state to cease and subsequently anticoagulation was stopped without recurrence of thromboembolism. However, she died 9 months after transplantation: iron overload, intensified by the transfusion demands of the transplant, was a major factor.
proteins
2024-10-25 | Biomechanics of phagocytosis of red blood cells by macrophages in the human spleen.
The clearance of senescent and altered red blood cells (RBCs) in the red pulp of the human spleen involves sequential processes of prefiltration, filtration, and postfiltration. While prior work has elucidated the mechanisms underlying the first two processes, biomechanical processes driving the postfiltration phagocytosis of RBCs retained at interendothelial slits (IES) are still poorly understood. We present here a unique computational model of macrophages to study the role of cell biomechanics in modulating the kinetics of phagocytosis of aged and diseased RBCs retained in the spleen. After validating the macrophage model using in vitro phagocytosis experiments, we employ it to probe the mechanisms underlying the kinetics of phagocytosis of mechanically altered RBCs, such as heated RBCs and abnormal RBCs in hereditary spherocytosis (HS) and sickle cell disease (SCD). Our simulations show pronounced deformation of the flexible and healthy RBCs in contrast to minimal shape changes in altered RBCs. Simulations also show that less deformable RBCs are engulfed faster and at lower adhesive strength than flexible RBCs, consistent with our experimental measurements. This efficient sensing and engulfment by macrophages of stiff RBCs retained at IES are expected to temper splenic congestion, a common pathogenic process in malaria, HS, and SCD. Altogether, our combined computational and in vitro experimental studies suggest that mechanical alterations of retained RBCs may suffice to enhance their phagocytosis, thereby adapting the kinetics of their elimination to the kinetics of their mechanical retention, an equilibrium essential for adequately cleaning the splenic filter to preserve its function.
2021-09-28 | Tangential flow filtration of haptoglobin.
Haptoglobin (Hp) is a plasma glycoprotein that scavenges cell-free hemoglobin (Hb). Hp has various potential therapeutic applications, but it has been mainly studied for treatment of acute hemolytic conditions that can arise from situations such as massive blood transfusion, infusion of stored red blood cells, severe burns, trauma, sepsis, radiation injury, and others. Therefore, Hp may also be beneficial during chronic hemolytic disease states such as hereditary spherocytosis, nocturnal hemoglobinuria, sickle-cell anemia, and malaria. Various methods have been developed to purify Hp from plasma or plasma fractions. However, none of these methods have exploited the large molecular weight (MW) range distribution of Hp polymers to easily isolate Hp from other plasma proteins. The present study used tangential flow filtration (TFF) to isolate polymeric Hp from plasma proteins using human Fraction IV (FIV) as the starting material. After removal of insoluble material from a suspension of FIV paste, the protein mixture was clarified on a 0.2 μm hollow fiber (HF) TFF filter. The clarified protein solution was then bracketed based on protein MW using HF filters with MW cut-offs (MWCOs) of 750, 500, and 100 kDa. Using untreated FIV, the Hp purity of the main bracket was ~75% with a total Hb binding capacity (HbBC) yield of 1.2 g starting from 500 g of FIV paste. However, pretreatment of FIV with fumed silica to remove lipoproteins increased Hp purity to >95% with a HbBC yield of 1.7 g per 500 g of FIV. Taken together this study provides a novel and scalable method to purify Hp from plasma or plasma fractions.
2021-04-06 | Successful Splenectomy Management in a Patient With Moderate Factor VII Deficiency and Concomitant Severe Hereditary Spherocytosis.
By the advent of the effective therapies for many coagulation diseases and hereditary spherocytosis (HS), patient's survival has been improved significantly; however, if patients are diagnosed late or left untreated, both diseases could ominously be life threatening. Concurrent occurring of factor VII (FVII) deficiency and HS is extremely rare and there is no literature report that explain this condition, thus far. In this study, we confronted a 9-year-old female patient diagnosed with HS and enlarged spleen as a result of this blood disorder. Given to her sever signs and symptoms of splenomegaly, she was candidate for emergent splenectomy. However, assessment of coagulation tests revealed a prolonged prothrombin time, suggesting the moderate FVII deficiency. With a multidisciplinary consultation, we decided to performed total splenectomy with prophylaxis administration of totally 6 doses of active recombinant FVII, initiated 1 hour before surgery and followed until 30 hours postoperation. As a result of cautious undertaken in Mofid Children's Hospital, the patient did not experience any hemostatic defect. Patient is now 14-year-old, generally well-being under regular surveillance of FVII deficiency.
2020-03-01 | Linkage of typically cytosolic peroxidases to erythrocyte membrane – A possible mechanism of protection in Hereditary Spherocytosis
Hereditary Spherocytosis (HS) is a non-immune hemolytic anemia associated to oxidative stress (OS), namely to the linkage of cytosolic antioxidant enzymes to the erythrocyte membrane.Our aims were to evaluate erythrocyte OS changes and the membrane linkage of peroxiredoxin 2 (Prx2), glutathione peroxidase (GPx) and catalase (CAT) in unsplenectomized (unspl) and splenectomized (spl) HS patients and to search for associations with clinical severity (in unspl HS patients).We studied 114 HS patients (74 unspl and 40 spl) and 30 healthy individuals and we evaluated membrane bound hemoglobin (MBH), membrane lipid-peroxidation (LPO), enzymatic activities of GPx and CAT and the amounts of membrane bound Prx2, GPx and CAT, as well as, clinical and analytical parameters for characterization of HS.We found that unspl HS patients showed clear signs of anemia and in spl HS, a correction to this anemia was observed; the latter patients presented higher levels of OS biomarkers, namely, MBH and LPO.CAT was detected in the membrane of all individuals (control and HS groups), while GPx and Prx2 were only present in HS patients; moreover, their linkage to the membrane (in HS) appears to be cumulative since membrane bound peroxidases amount was higher as the number of peroxidases detected increased.MBH increased with the number/amount of membrane bound peroxidases, however LPO levels remained similar.In conclusion, our data suggest that the binding of these typically cytosolic peroxidases to erythrocyte membrane may be part of a mechanism of membrane protection to maintain its integrity by possibly regulating LPO.
2019-09-10 | Treatment of a Child With Submassive Pulmonary Embolism Associated With Hereditary Spherocytosis Using Ultrasound-Assisted Catheter-Directed Thrombolysis
Background: The clinical presentation of hereditary spherocytosis varies from no symptoms to severe hemolytic anemia requiring splenectomy. Splenectomy imposes the risk of hypercoagulability and acute pulmonary embolism. Catheter-directed thrombolysis is an established treatment for submassive pulmonary embolism in adults. However, the literature regarding its use in children is limited. Case Report: We present the case of a 12-year-old male with hereditary spherocytosis who was diagnosed with pulmonary embolism and successfully treated with catheter-directed thrombolysis. The patient was initially treated with 10.5 mg of recombinant tissue plasminogen activator (r-tPA) delivered over 8 hours. However, because of minimal clinical and hemodynamic improvement, a second course of thrombolytic was administered for an additional 24 hours (25 mg of r-tPA), and the treatment resulted in marked clinical and hemodynamic improvement. Clot resolution was confirmed via angiography. The patient was discharged on enoxaparin and with regular follow-up. One year later, the patient was asymptomatic on enoxaparin. Conclusion: This case demonstrates that catheter-based treatment of submassive pulmonary embolism restores hemodynamic stability and thus is an alternative to surgery or systemic thrombolysis, even in the pediatric setting. While catheter-directed thrombolysis is a safe and effective alternative to systemic thrombolysis, further research is needed to establish appropriate dosing and indications in the adolescent population.
gene therapies
2026-07-23 | Hereditary Spherocytosis in a Child due to a Deletion in β‐Spectrin Detected by Low‐Input DNA Long‐Read Whole‐Genome Sequencing
The authors declare no conflicts of interest. Relevant data are available from the corresponding author upon reasonable request. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
2026-03-19 | Symptomatic Recurrent Splenomegaly Following Partial Splenectomy in Patients With Hereditary Spherocytosis.
Hereditary spherocytosis (HS) is an inherited hematologic disorder characterized by spherical erythrocytes that are prematurely destroyed in the spleen. Total splenectomy (TS) and partial splenectomy (PS) are surgical interventions used to manage HS, but long-term outcomes, including recurrence of splenomegaly and splenomegaly-related symptoms, remain poorly understood. This study aims to evaluate the long-term recurrence of splenomegaly and splenomegaly-related symptoms in children with HS who underwent PS versus TS at a single institution between 2008 and 2020. A retrospective chart review of children with HS who underwent TS or PS was performed. The primary end point was the long-term recurrence of splenomegaly and splenomegaly-related symptoms. Variables collected included age, sex, surgical method (PS vs. TS), postoperative hematologic markers, splenic volume, postoperative complications, length of hospital stay, recurrence of splenomegaly, and need for completion splenectomy. Symptomatic recurrent splenomegaly is defined as splenic volume > 450 mL and the presence of symptoms directly attributable to the spleen and its effects on adjacent organs or hemolysis. Statistical analysis included comparisons of continuous variables using a Kruskal-Wallis test and categorical variables using a Fisher's exact test. Forty-four patients with HS met the inclusion criteria for the study. Of these, 31 (71%) patients underwent laparoscopic PS and 13 (30%) patients underwent laparoscopic TS. TS was associated with significantly less intraoperative blood loss (p = 0.003), shorter hospital stays (p = 0.01), and greater reduction in hemolysis compared to PS, as evidenced by lower postoperative bilirubin levels and reticulocyte counts (both p < 0.001). Eighteen (58%) PS patients experienced recurrent splenomegaly, and six (19%) PS patients experienced splenomegaly-related symptoms leading to completion splenectomy. Among the six patients who required completion splenectomy, intraoperative hemorrhage requiring conversion to open procedure occurred in half. The median time to need completion splenectomy was 10.5 years (range, 3-15 years). TS offers more significant long-term hematologic improvements but comes with the loss of immune function and increased risk of overwhelming post-splenectomy infection (OPSI). PS, while preserving some splenic function and theoretically reducing OPSI risk, carries a higher risk of recurrent symptomatic splenomegaly and may require additional surgeries. These findings highlight the importance of long-term follow-up for HS patients who undergo PS and the need to balance the advantages and risks of both surgical approaches.
2026-03-05 | A novel variant of the erythrocyte spectrin-beta gene (SPTB) causing hereditary spherocytosis in a Sri Lankan child
No abstract available
2026-02-13 | Frequency and characterization of Parvovirus B19 infections in children with hematologic diseases: a single-center retrospective analysis
Introduction: Parvovirus B19 (PVB19) represents a clinically relevant pathogen in individuals with hematologic disorders. While infection may remain clinically silent, it can also precipitate significant hematologic complications, including severe anemia or aplastic crisis. This study aimed to evaluate the prevalence of PVB19 infection in pediatric patients hospitalized for hematologic diseases and to delineate the clinical profile of active infections. Material and methods: The cohort consisted of 103 children admitted to the Department of Pediatric Hematology, Oncology, and Transplantology at the Children’s University Hospital in Lublin between 2023 and 2025. Serological testing for IgM and IgG antibodies against PVB19 was performed using enzyme-linked immunosorbent assay (ELISA). Patients were stratified into two groups: those with active infection, defined as IgM ≥ 1.1, and those with negative IgM titers. Analyses included demographic characteristics, laboratory indices, hospitalization duration, transfusion requirements, and infection-related complications. Results: IgM seropositivity was identified in 13 patients (12.6%). The most frequent underlying hematologic disorder was hereditary spherocytosis (n = 3). Hospitalization ranged from 1 to 113 days. Eight patients required red blood cell transfusions. The most frequent clinical features included fever (n = 6) and upper respiratory tract infection (n = 3). Statistical analysis revealed differences in infection prevalence across age categories (P = 0.02), with the highest incidence in the 4–6-year age group (n = 7). Conclusions: The clinical spectrum of PVB19 infection varied from mild disease to severe hematologic complications. No correlation between sex and susceptibility to PVB19 infection was observed. The results suggest a predominance of infections in early childhood; however, confirmation requires validation in larger study cohorts.
2026-01-01 | Decoding hereditary spherocytosis: Unveiling the genes as a potential causative agent
Hereditary spherocytosis (HS) is the most common inherited hemolytic anemia in populations of northern European descent, arising from mutations in genes encoding key erythrocyte membrane proteins, including ANK1 , SPTB , SLC4A1 , SPTA1 , and EPB42 . These genetic defects disrupt the vertical linkages between the red blood cell (RBC) plasma membrane and its underlying cytoskeleton, reducing RBC deformability and leading to characteristic spherocytosis, premature hemolysis, and accelerated splenic clearance. Inheritance is predominantly autosomal dominant, although autosomal recessive forms occur, particularly involving SPTA1 and EPB42. Clinically, HS manifests with anemia, jaundice, splenomegaly, and complications such as cholelithiasis. This study aimed to identify and characterize pathogenic variants in primary HS genes, establish genotype–phenotype correlations, and enhance diagnostic accuracy to guide personalized management within a defined cohort. Diagnostic advancements, notably the tests of next-generation sequencing and the eosin-5-maleimide binding test, have improved the detection of genetic heterogeneity, yet regional underdiagnosis persists. A comprehensive understanding of the HS genetic spectrum is therefore critical not only for precise diagnosis and optimized patient care but also for informing the development of future gene-targeted therapies, including CRISPR-based approaches. Regional epidemiological investigations, including limited data from Iraq, suggest that HS remains underdiagnosed despite its significant clinical impact. A comprehensive understanding of the HS genetic spectrum is imperative for accurate diagnosis, optimized personalized management, and the eventual development of gene-based therapeutic interventions.
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