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European Journal of Haematology Nov 2023Subtotal or total splenectomy are recommended in severe and should be considered in intermediate forms of hereditary spherocytosis (HS). Data on laparoscopic subtotal...
INTRODUCTION
Subtotal or total splenectomy are recommended in severe and should be considered in intermediate forms of hereditary spherocytosis (HS). Data on laparoscopic subtotal splenectomy (LSTS) in HS patients are sparse.
METHODS
Thirty three patients with HS (median age 10.7 years (yrs), range 1.8-15.5) underwent LSTS. Baseline and follow-up investigation included haematological parameters, microscopic analysis of pitted erythrocytes (pitE), and B-cell subpopulations assessed by flow cytometry. Results were compared to those of non-splenectomised HS patients, HS patients after total splenectomy (TS), and healthy individuals.
RESULTS
After LSTS, haemoglobin levels were normalised in all patients. During median long-term follow-up of 3.9 yrs (range 1.1-14.9), only four patients presented mild anaemia. Despite re-growing of the remnant spleen none of the patients required a second surgical intervention. As compared to TS, PitE in LSTS patients were significantly lower and indicated normal to only moderately decreased spleen function. Relative but not absolute IgM memory B-cell counts were reduced in both LSTS and TS patients.
CONCLUSIONS
LSTS is effective for the treatment of patients with HS. A small remnant spleen is sufficient to provide adequate phagocytic function and to induce a pool of IgM memory B-cells.
Topics: Humans; Child; Splenectomy; Spleen; Spherocytosis, Hereditary; Laparoscopy; Immunoglobulin M
PubMed: 37700575
DOI: 10.1111/ejh.14077 -
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 -
Clinica Chimica Acta; International... Aug 2023Osmotic gradient ektacytometry is an important method for diagnosis of red blood cell membrane disorders. For interpretation of the osmoscan parameters on the...
BACKGROUND AND AIMS
Osmotic gradient ektacytometry is an important method for diagnosis of red blood cell membrane disorders. For interpretation of the osmoscan parameters on the ektacytomety, an age-matched control sample drawn at the same time is recommended for direct comparison. However, this can be challenging for laboratories to fulfil, especially when ektacytometry is performed in children. Therefore, the aim of this study was to evaluate the influence of age and sex on the osmoscan parameters.
MATERIALS AND METHODS
Blood samples from 231 subjects were analyses on a LoRRca MaxSIS. Data were investigated for need of partitioning by age and sex. After outlier detection, reference intervals (RIs) for osmoscan parameters were estimated.
RESULTS
For all parameters except EImin, lower values were observed in infants < 3 month (N = 50) than in all other age group. Hence, RIs were calculated separately for this age group. For EImin, a unified RI was calculated. No difference between sexes was observed for any of the parameters.
CONCLUSION
Lower RIs and a left shift in the osmoscan curves were observed in infants < 3 months compared with older subjects. Hence, age-matched controls are necessary when evaluating ektacytometry in newborns, but can be ignored in older children and adults. This will ease the laboratory workflow when performing ektacytometry.
Topics: Infant, Newborn; Adult; Child; Infant; Humans; Osmosis; Erythrocyte Membrane; Laboratories; Workflow
PubMed: 37659465
DOI: 10.1016/j.cca.2023.117532 -
Blood Cells, Molecules & Diseases Nov 2023Reaching a precise diagnosis in rare inherited anemia is extremely difficult and challenging, especially in areas with limited use of genetic studies, which makes...
BACKGROUND
Reaching a precise diagnosis in rare inherited anemia is extremely difficult and challenging, especially in areas with limited use of genetic studies, which makes undiagnosed anemia a unique clinical entity in tertiary hematology centers. In this study, we aim at plotting a stepwise diagnostic approach in children with undiagnosed anemia while identifying indications for genetic testing.
PATIENTS AND METHODS
A one-year cross-sectional study involved 44 children and adolescents with undiagnosed anemia after undergoing an initial routine panel of investigations. They were classified based on mean corpuscular volume (MCV) into 3 groups: microcytic (n = 19), normocytic (n = 14) and macrocytic (n = 11). An algorithm that included four levels of investigations was devised for each category.
RESULTS
After applying a systematic diagnostic approach, 33 patients (75 %) were diagnosed of whom 7 (15 %) had combined diagnoses, while 11 (25 %) patients remained undiagnosed. Based on the first, second, third and fourth levels of investigations, patients were diagnosed, respectively, as follows: of the 11 patients, 7 were microcytic, 3 normocytic and 1 macrocytic; of the 7 patients, 2 were microcytic, 2 normocytic, and 3 macrocytic; of 10 patients, 5 were microcytic, 4 normocytic and 1 macrocytic; finally, of the 16 patients, 8 were microcytic, 6 normocytic and 2 macrocytic. Numbers recorded appear higher than the actual number of the patients because some of them were diagnosed by more than one level of investigation. The diagnoses obtained in the microcytic group showed hemoglobinopathies, iron refractory iron deficiency anemia (IRIDA), membrane defects, sideroblastic anemia, hypo-transferrinemia, a combined diagnosis of sickle cell trait and pyropoikilocytosis. The diagnoses also showed a combined diagnosis of hereditary spherocytosis (HS) and alpha thalassemia minor, and a combined diagnosis of iron deficiency anemia and beta thalassemia minor, while 15 % remained undiagnosed. In the normocytic group, the diagnosis revealed autosomal recessive (AR) HS, vitamin B12 deficiency, pyruvate kinase deficiency (PKD), congenital dyserythropoietic anemia (CDA) type I, Diamond Blackfan anemia and beta thalassemia major. In addition, it showed a combined diagnosis of AR HS and CDA type II, a combined diagnosis of AR HS and PKD, and a combined diagnosis of dehydrated stomatocytosis (DHS) and G6PD carrier, meanwhile 20 % remained undiagnosed. Finally, the macrocytic group was diagnosed by vitamin B12 deficiency, sideroblastic anemia, PKD, a combined diagnosis of PKD and G6PD deficiency carrier, while 45 % remained undiagnosed.
CONCLUSION
Conducting a stepwise approach with different levels of investigations may help reach the diagnosis of difficult anemia without having to resort to unnecessary investigations. Combined diagnosis is an important cause of undiagnosed anemia, especially in countries with high frequency of consanguinity. The remaining 25 % of the patients continued to be undiagnosed, requiring more sophisticated investigations.
Topics: Adolescent; Humans; Child; Anemia, Iron-Deficiency; Anemia, Sideroblastic; beta-Thalassemia; Cross-Sectional Studies; Developing Countries; Vitamin B 12 Deficiency
PubMed: 37558589
DOI: 10.1016/j.bcmd.2023.102779 -
Blood Cells, Molecules & Diseases Nov 2023We report here an instructive case referred at 16 months-old for exploration of hemolysis without anemia (compensated anemia with reticulocytosis). The biology tests...
Next generation sequencing (NGS) interest in deciphering erythrocyte molecular defects' association in red cell disorders: Clinical and erythrocyte phenotypes of patients with mutations inheritance in PIEZO1, Spectrin ß1, RhAG and SLC4A1.
We report here an instructive case referred at 16 months-old for exploration of hemolysis without anemia (compensated anemia with reticulocytosis). The biology tests confirmed the hemolysis with increased total and indirect bilirubin. The usual hemolysis diagnosis tests were normal (DAT, G6PD, PK, Hb electrophoresis) except cytology and ektacytometry suggesting an association of multiple red blood cell (RBC) membrane disorders. This led us to propose a molecular screening analysis using targeted-Next Generation Sequencing (t-NGS) with a capture technique on 93 genes involved in RBC and erythropoiesis defects. We identified 4 missense heterozygous allelic variations, all of them were described without any significance (VUS) in the SLC4A1, RhAG, PIEZO1 and SPTB genes. The study of the familial cosegregation and research functional tests allowed to decipher the role of at least two by two genes in the phenotype and the hemolytic disease of this young patient. Specialized t-NGS panel (or virtual exome/genome sequencing) in a disease-referent laboratory and the motivated collaboration of clinicians, biologists and scientists should be the gold standard for improving the diagnosis of the patients affected with RBC diseases or rare inherited anemias.
Topics: Humans; Spherocytosis, Hereditary; Spectrin; High-Throughput Nucleotide Sequencing; Hemolysis; Mutation; Erythrocytes; Hematologic Diseases; Phenotype; Anion Exchange Protein 1, Erythrocyte; Ion Channels
PubMed: 37516005
DOI: 10.1016/j.bcmd.2023.102780 -
Veterinary Sciences Jun 2023The immunodiagnostic assessment of dogs suspected of having immune-mediated hemolytic anemia (IMHA) is based on persistent autoagglutination of erythrocytes (after three...
The Indirect Antiglobulin (Coombs') Test Is Specific but Less Sensitive Than the Direct Antiglobulin Test for Detecting Anti-Erythrocytic Autoantibodies and Thereby Immune-Mediated Hemolytic Anemia in Dogs.
The immunodiagnostic assessment of dogs suspected of having immune-mediated hemolytic anemia (IMHA) is based on persistent autoagglutination of erythrocytes (after three saline washes), marked spherocytosis, and a positive direct antiglobulin (Coombs') test (DAT). However, the value of using the indirect antiglobulin test (IAT) for the detection of anti-erythrocytic autoantibodies in serum from dogs suspected of having IMHA is unclear. To evaluate the IAT, leftover serum samples from a large cohort of 94 dogs suspected of having IMHA and for which DAT results were known were incubated with DAT- erythrocytes, and five IAT techniques were performed (in part with different reagents and temperatures): microtiter plate (MICRO), microcapillary, laboratory gel column, gel minitube kit (GEL KIT), and immunochromatographic strip kit. Two IAT techniques (MICRO at 37 °C and GEL KIT with rabbit anti-dog polyvalent reagent) detected autoantibodies against erythrocytes in serum from 53% and 57% of DAT+ dogs, respectively, while other IATs performed less well. Moreover, while the analytic specificity of the IAT methods compared to the DAT ranged from 96-100%, the sensitivity range was only 9-57%. Thus, we still recommend DAT for diagnosis and monitoring of IMHA in dogs but conclude that a positive IAT result may aid diagnostically when serum is available, but fresh red blood cells are not.
PubMed: 37505821
DOI: 10.3390/vetsci10070415 -
Hematology (Amsterdam, Netherlands) Dec 2023Severe autoimmune hemolytic anemia complicating hereditary spherocytosis is life threatening and has not been described in a case report. Here, we report a case in which...
BACKGROUND
Severe autoimmune hemolytic anemia complicating hereditary spherocytosis is life threatening and has not been described in a case report. Here, we report a case in which this intractable disease was treated successfully with glucocorticoids and cyclosporine.
CASE PRESENTATION
A 25-year-old female patient with hereditary spherocytosis developed severe autoimmune hemolytic anemia after respiratory syncytial virus infection. Her hemoglobin level was 26 g/L and various anti-red blood cell antibodies were detected in her serum, making blood matching difficult. Glucocorticoid monotherapy was ineffective. With the addition of cyclosporine (50 mg/12 h), the patient's hemoglobin level increased significantly and the symptoms associated with anemia were greatly relieved.
CONCLUSION
In patients with severe autoimmune hemolytic anemia, especially when the presence of multiple anti-red blood cell antibodies and alloantibodies interferes with blood matching, a glucocorticoid-cyclosporine regimen may be tried.
Topics: Female; Humans; Adult; Anemia, Hemolytic, Autoimmune; Glucocorticoids; Cyclosporine; Spherocytosis, Hereditary; Hemoglobins; Anemia, Hemolytic
PubMed: 37504499
DOI: 10.1080/16078454.2023.2235832 -
JPMA. the Journal of the Pakistan... Apr 2023To evaluate Hem-o-Lok polymer clips' feasibility, safety and cost-effectiveness in controlling the splenic pedicle during paediatric laparoscopic splenectomy.
OBJECTIVES
To evaluate Hem-o-Lok polymer clips' feasibility, safety and cost-effectiveness in controlling the splenic pedicle during paediatric laparoscopic splenectomy.
METHOD
The prospective study was conducted from May 2019 to December 2021 at Kafrelsheikh University Hospital, Egypt, and comprised children of either gender aged <18 years who had benign haematological diseases and were indicated for laparoscopic splenectomy. During the procedure, Hem-o-Lok clips were used for controlling the splenic pedicle. Patients were encouraged to ambulate the same day, and the drain was removed 24hours postoperatively. The cases were followed up for three months postoperatively.
RESULTS
Of the 23 subjects, 11(47.8%) were boys and 12(52.2%) were girls. The overall mean age was 8.74±3.44 years (range: 4-15 years). There were 6(26%) cases of spherocytosis, 1(4.3%) immune thrombocytopenic purpura and 16(69.6%) with thalassemia major. The mean operative time was 93.43±29.87 minutes(range: 65-180 minutes). There was no conversion to open splenectomy and no mortality. There were 2(8.7%) cases of minor and 1(4.3%) of major intraoperative bleeding. All the 3(100%) cases were controlled laparoscopically. No postoperative bleeding occurred and no cases required postoperative blood transfusion.
CONCLUSIONS
Controlling both the splenic artery and vein using Hem-o-Lok clips was found to be feasible, safe and cost-effective.
Topics: Male; Female; Humans; Child; Child, Preschool; Splenectomy; Prospective Studies; Spleen; Laparoscopy; Postoperative Hemorrhage
PubMed: 37482863
DOI: 10.47391/JPMA.EGY-S4-45 -
Indian Journal of Nephrology 2023In this case study, we report an adult patient presenting with generalized weakness, marked anemia, spherocytosis, and no features of thalassemia. The patient was...
In this case study, we report an adult patient presenting with generalized weakness, marked anemia, spherocytosis, and no features of thalassemia. The patient was treated for suspicion of autoimmune hemolytic anemia but was recalcitrant to treatment. Genetic analysis revealed the patient to be homozygous for c.2573C>A (p.Ala858Asp). Distal renal tubular acidosis (dRTA) can be caused by mutations in , which encodes the Cl/HCO exchanger of the renal type A intercalated cell, kidney AE1. variants have been reported in dRTA patients from North America, Europe, and Southeast Asia. In some rare instances, dRTA can present with hemolytic anemia resulting in marked anemia that is not responsive to standard interventions. This report identifies an autosomal recessive inheritance pattern for variants in a patient presenting with dRTA and hemolytic anemia.
PubMed: 37448902
DOI: 10.4103/ijn.ijn_210_21 -
IDCases 2023
PubMed: 37434610
DOI: 10.1016/j.idcr.2023.e01820