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Clinical Case Reports Jun 2024When a person has both HS and beta-thalassemia, their clinical symptoms tend to be less severe. This is because these two conditions have contrasting features. If the...
KEY CLINICAL MESSAGE
When a person has both HS and beta-thalassemia, their clinical symptoms tend to be less severe. This is because these two conditions have contrasting features. If the clinical symptoms and laboratory results cannot be solely attributed to hemolytic anemia, it is important to consider the possibility of another form of hemolytic anemia coexisting.
ABSTRACT
We present a 26-year-old woman who has been experiencing abdominal pain, jaundice, and anemia for the past 15 years. Initially, she was diagnosed with gallstones and splenomegaly, but after a thorough hematology examination conducted by expert colleagues, it was discovered that she had both beta-thalassemia and hereditary spherocytosis. The osmotic fragility test confirmed this diagnosis. The patient was advised to undergo both splenectomy and cholecystectomy procedures. It is worth noting that the co-occurrence of these two conditions is rare.
PubMed: 38868122
DOI: 10.1002/ccr3.9080 -
Sisli Etfal Hastanesi Tip Bulteni 2023The objective of the study is to present the demographic characteristics, clinical and laboratory features and outcome of our patients with hereditary spherocytosis (HS).
OBJECTIVES
The objective of the study is to present the demographic characteristics, clinical and laboratory features and outcome of our patients with hereditary spherocytosis (HS).
METHODS
Demographic, clinical, and laboratory data; complications; and splenectomy results were analyzed retrospectively. The severity of the disease was scaled according to Eber's criteria.
RESULTS
Sixty-nine patients (42 boys, 27 girls, median age: 3 years) were eligible. Sixty-eight percent of the patients had a history of neonatal jaundice. The complaints at admission were jaundice (71%), fatigue (27.5%), fainting (4.3%), and pallor (4.3%). The median follow-up duration was 8.5 years. According to Eber's criteria, three (4.3%), 57 (82.6%), and nine (13.1%) patients had mild, moderate, and severe diseases, respectively. Thirty-six patients (52.1%) had a splenectomy. Following splenectomy, we observed a significant rise in hemoglobin levels and a decline in indirect bilirubin levels. Post-operative thrombocytosis was common, with a tendency to fall and stabilize after 1 month. There were no thromboembolic complications.
CONCLUSION
In spite of the high rate of consanguinity, familial history of HS, and neonatal jaundice in our study group, the majority of the HS patients were identified relatively late, about 3 years. This finding shows that HS might be insufficiently acknowledged by primary care. Splenectomy, in selected cases, may reduce the need for transfusions. Post-splenectomy transient thrombocytosis is common and has a benign course.
PubMed: 38268662
DOI: 10.14744/SEMB.2023.60370 -
JCI Insight Oct 2023Hereditary spherocytosis (HS) is the most common, nonimmune, hereditary, chronic hemolytic anemia after hemoglobinopathies. The genetic defects in membrane function...
Hereditary spherocytosis (HS) is the most common, nonimmune, hereditary, chronic hemolytic anemia after hemoglobinopathies. The genetic defects in membrane function causing HS lead to perturbation of the RBC metabolome, with altered glycolysis. In mice genetically lacking protein 4.2 (4.2-/-; Epb42), a murine model of HS, we showed increased expression of pyruvate kinase (PK) isoforms in whole and fractioned RBCs in conjunction with abnormalities in the glycolytic pathway and in the glutathione (GSH) system. Mitapivat, a PK activator, metabolically reprogrammed 4.2-/- mouse RBCs with amelioration of glycolysis and the GSH cycle. This resulted in improved osmotic fragility, reduced phosphatidylserine positivity, amelioration of RBC cation content, reduction of Na/K/Cl cotransport and Na/H-exchange overactivation, and decrease in erythroid vesicles release in vitro. Mitapivat treatment significantly decreased erythrophagocytosis and beneficially affected iron homeostasis. In mild-to-moderate HS, the beneficial effect of splenectomy is still controversial. Here, we showed that splenectomy improves anemia in 4.2-/- mice and that mitapivat is noninferior to splenectomy. An additional benefit of mitapivat treatment was lower expression of markers of inflammatory vasculopathy in 4.2-/- mice with or without splenectomy, indicating a multisystemic action of mitapivat. These findings support the notion that mitapivat treatment should be considered for symptomatic HS.
Topics: Animals; Mice; Disease Models, Animal; Spherocytosis, Hereditary; Erythrocytes; Anemia, Hemolytic
PubMed: 37676741
DOI: 10.1172/jci.insight.172656 -
International Journal of Molecular... Nov 2023Congenital defects of the erythrocyte membrane are common in northern Europe and all over the world. The resulting diseases, for example, hereditary spherocytosis (HS),...
Congenital defects of the erythrocyte membrane are common in northern Europe and all over the world. The resulting diseases, for example, hereditary spherocytosis (HS), are often underdiagnosed, partly due to their sometimes mild and asymptomatic courses. In addition to a broad clinical spectrum, this is also due to the occasionally complex diagnostics that are not available to every patient. To test whether next-generation sequencing (NGS) could replace time-consuming spherocytosis-specific functional tests, 22 consecutive patients with suspected red cell membranopathy underwent functional blood tests. We were able to identify the causative genetic defect in all patients with suspected HS who underwent genetic testing ( = 17). The sensitivity of the NGS approach, which tests five genes ( (gene product: ankyrin1), (erythrocyte membrane protein band4.2), (band3), (α-spectrin), and (β-spectrin)), was 100% (95% confidence interval: 81.5-100.0%). The major advantage of genetic testing in the paediatric setting is the small amount of blood required (<200 µL), and compared to functional assays, sample stability is not an issue. The combination of medical history, basic laboratory parameters, and an NGS panel with five genes is sufficient for diagnosis in most cases. Only in rare cases, a more comprehensive functional screening is required.
Topics: Humans; Child; Ankyrins; Mutation; Spherocytosis, Hereditary; Spectrin; Cytoskeletal Proteins; High-Throughput Nucleotide Sequencing
PubMed: 38069343
DOI: 10.3390/ijms242317021 -
Cureus Feb 2024Hereditary spherocytosis/elliptocytosis is a non-immune hemolytic anemia caused by an alteration in the erythrocyte membrane that predisposes the cell to its lysis. This...
Hereditary spherocytosis/elliptocytosis is a non-immune hemolytic anemia caused by an alteration in the erythrocyte membrane that predisposes the cell to its lysis. This report presents a case of a 42-year-old woman with a history of spontaneous abortion, associated with postpartum bleeding, chronic anemia, and premature menopause. After five years, she consulted due to alterations in the state of consciousness and severe symptomatic hyponatremia, with a diagnosis of hypopituitarism, explained by a late Sheehan syndrome. During hospitalization, she developed non-immune hemolytic anemia associated with a positive osmotic fragility test. A diagnosis of hereditary spherocytosis/elliptocytosis was made. We correlate blood hypoosmolarity as a trigger with the in vitro hypotonic solution of the osmotic fragility test for the diagnosis of this disease. This association is not reported in the literature; in our case, we show the concomitant improvement of anemia with the increase in sodium levels and hormonal replacement.
PubMed: 38435165
DOI: 10.7759/cureus.53417 -
Frontiers in Pediatrics 2024
PubMed: 38633330
DOI: 10.3389/fped.2024.1403651 -
Perioperative Medicine (London, England) Jun 2024Due to the distinctive nature of cardiac surgery, patients suffering from hereditary spherocytosis (HS) are potentially at a high risk of perioperative complications... (Review)
Review
BACKGROUND
Due to the distinctive nature of cardiac surgery, patients suffering from hereditary spherocytosis (HS) are potentially at a high risk of perioperative complications resulting from hemolysis. Despite being the most prevalent cause of hereditary chronic hemolysis, the standards of surgical management are based solely on expert opinion.
OBJECTIVE
We analyze the risk of hemolysis in HS patients after cardiac surgery based on a systematic review of the literature. We also describe a case of a patient with hereditary spherocytosis who underwent aortic valve repair.
METHODS
This systematic review was registered in the PROSPERO international prospective register of systematic reviews (CRD42023417666) and included records from Embase, MEDLINE, Web of Science, and Google Scholar databases. The case study investigates a 38-year-old patient who underwent surgery for an aortic valve defect in mid-2022.
RESULTS
Of the 787 search results, 21 studies describing 23 cases of HS undergoing cardiac surgery were included in the final analysis. Hemolysis was diagnosed in five patients (one coronary artery bypass graft surgery, two aortic valve bioprosthesis, one ventricular septal defect closure, and one mitral valve plasty). None of the patients died in the perioperative period. Also, no significant clinical hemolysis was observed in our patient during the perioperative period.
CONCLUSIONS
The literature data show that hemolysis is not common in patients with HS undergoing various cardiac surgery techniques. The typical management of a patient with mild/moderate HS does not appear to increase the risk of significant clinical hemolysis. Commonly accepted beliefs about factors inducing hemolysis during cardiac surgery may not be fully justified and require further investigation.
PubMed: 38858770
DOI: 10.1186/s13741-024-00411-w -
Blood Advances Sep 2023Splenectomy improves the clinical parameters of patients with hereditary spherocytosis, but its potential benefit to red blood cell (RBC) functionality and the mechanism...
Splenectomy improves the clinical parameters of patients with hereditary spherocytosis, but its potential benefit to red blood cell (RBC) functionality and the mechanism behind this benefit remain largely overlooked. Here, we compared 7 nonsplenectomized and 13 splenectomized patients with mutations in the β-spectrin or the ankyrin gene. We showed that hematological parameters, spherocyte abundance, osmotic fragility, intracellular calcium, and extracellular vesicle release were largely but not completely restored by splenectomy, whereas cryohemolysis was not. Affected RBCs exhibited decreases in β-spectrin and/or ankyrin contents and slight alterations in spectrin membrane distribution, depending on the mutation. These modifications were found in both splenectomized and nonsplenectomized patients and poorly correlated with RBC functionality alteration, suggesting additional impairments. Accordingly, we found an increased abundance of septins, small guanosine triphosphate-binding cytoskeletal proteins. Septins-2, -7, and -8 but not -11 were less abundant upon splenectomy and correlated with the disease severity. Septin-2 membrane association was confirmed by immunolabeling. Except for cryohemolysis, all parameters of RBC morphology and functionality correlated with septin abundance. The increased septin content might result from RBC maturation defects, as evidenced by (1) the decreased protein 4.2 and Rh-associated glycoprotein content in all patient RBCs, (2) increased endoplasmic reticulum remnants and endocytosis proteins in nonsplenectomized patients, and (3) increased lysosomal and mitochondrial remnants in splenectomized patients. Our study paves the way for a better understanding of the involvement of septins in RBC membrane biophysical properties. In addition, the lack of restoration of septin-independent cryohemolysis by splenectomy may call into question its recommendation in specific cases.
Topics: Humans; Spectrin; Septins; Splenectomy; Ankyrins; Spherocytosis, Hereditary; Erythrocytes
PubMed: 36753606
DOI: 10.1182/bloodadvances.2022009114