Temporal trends of splenectomy in pediatric hospitalizations with hereditary spherocytosis from 2000 to 2019: A national survey.

BACKGROUND: Total and partial splenectomy are used in pediatric patients with hereditary spherocytosis to resolve anemia and hemolytic complications. PROCEDURE: Data from the Healthcare Cost and Utilization Project's Kid's Inpatient Database was used to profile and describe temporal trends in pediatric (≤18 years) hospital admissions in the United States from 2000 to 2019 data release years. Survey sampling methods were used to produce national estimates. RESULTS: From 2000 to 2019, the use of splenectomy declined overall, from 427 to 206 weighted procedures (difference = 222, 95% confidence interval [CI]: 124-320; p < .0001); the risk of undergoing splenectomy during admission also declined from 56.7% to 38.7% (risk difference = 17.9 percentage points [p.p.], 95% CI: 9.7-26.1; p < .0001). Total splenectomy was mostly used. Age at time of splenectomy increased 10.2 years (difference = 1.6 years, 95% CI: 0.6-2.7; p = .0018). The risk of splenectomy increased with age until 10 years, then leveled off until 18 years. The proportion of children aged ≤5 years undergoing splenectomy decreased from 27.7% to 11.2% in 2019 (risk difference: 16.5 p.p., 95% CI: 7.3-25.7; p = .0004). The strongest clinical predictors of splenectomy, adjusting for patient- and hospital-level characteristics, were a co-diagnosis of symptomatic cholelithiasis (adjusted odds ratio [aOR] = 3.18, 95% CI: 1.92-5.28; p < .0001) and splenomegaly or hypersplenism (aOR = 2.52, 95% CI: 1.74-3.65; p < .0001). Risk of splenectomy with splenomegaly or hypersplenism increased over time. CONCLUSION: Splenectomy was delayed until age greater than 10 years. Older age, co-diagnosis with splenomegaly or hypersplenism, or symptomatic cholelithiasis were strongest clinical predictors of splenectomy. Conservative management of hereditary spherocytosis appears to be more common.

[Clinical and genotypic analysis of hereditary spherocytosis combined with cholestasis among pediatric patients].

Objective: To understand the clinical and genetic characteristics of hereditary spherocytosis (HS) combined with cholestasis among pediatric patients. Methods: 12 cases of HS children accompanied by cholestasis at Hunan Children's Hospital were selected as the research subjects between January 2013 and December 2022. Clinical data were collected. Whole-exome sequencing was performed by second-generation sequencing. Suspected pathogenic mutation sites were verified by Sanger sequencing. Results: All pediatric patients were admitted to the hospital due to their yellow skin tone. Eight cases (66.67%) had a positive family history. The clinical manifestations were jaundice, splenomegaly (12/12), abdominal pain, anemia (4/12), and hepatomegaly (5/12). All pediatric patients had decreased hemoglobin, an increased reticulocyte ratio, total bilirubin and direct bilirubin, a positive erythrocyte fragility test, and remarkable spherical erythrocytes in their peripheral blood. Seven cases had elevated aminotransferase; four cases had severely elevated aminotransferase and bilirubin; eight cases had biliary calculi; and two cases had a dilated biliary tract. Liver pathological examination showed mild damage to the liver cells (G1S1) in three pediatric cases. Five children had a total of six unreported mutations: SPTB gene c.2431_2450del, c.4974-2A > G, c.2575G > A, and exon 22-35 deletion; ANK1 gene: c.2379-2380delC; and c .6dupC. Children still had abnormal bilirubin levels following treatment. Two pediatric cases underwent splenectomy. Bilirubin and hemoglobin levels returned to normal after surgery. Conclusion: Children with HS may experience cholestasis, and those with poor treatment results may consider undergoing a splenectomy. Six new types of variants have expanded the HS gene mutation spectrum.

Long-term haematological response and maintained immunological function after laparoscopic subtotal splenectomy in patients with hereditary spherocytosis.

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.

Splenectomy improves erythrocyte functionality in spherocytosis based on septin abundance, but not maturation defects.

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 ß-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 ß-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.

Treatment of asymptomatic gallstones in children with hereditary spherocytosis requiring splenectomy.

BACKGROUND: Gallstones are common in hereditary spherocytosis (HS) and other chronic hemolytic diseases, with most affected patients being asymptomatic. Whether and how asymptomatic gallstones should be treated is controversial. METHODS: We conducted a retrospective cohort study of pediatric patients with HS and asymptomatic gallstones to compare the clinical outcomes between the observation group (followed up with gallstones in situ) and the intervention group (cholecystectomy or cholecystolithotomy). The primary outcome was the composite of adverse outcomes, including gallstone-associated, gallbladder surgery-associated, and splenectomy-associated events. Secondary outcomes included the changes in the size and number of gallstones and the recurrence of gallstones. RESULTS: Fifty-two patients were included (38 in the observation group and 14 in the intervention group), with a mean follow-up length of 5.2 years. Patients in the intervention group had a lower incidence of primary outcomes (7.1% vs. 42.1%) than patients in the observation group (OR, 0.12; 95%CI, 0.01-0.99). Patients with gallstones >5 mm in diameter had the highest risk of adverse events (47.4%). In the observation group, gallstone growth, disappearance, and stability were observed in 19.4%, 29.0%, and 51.6% of splenectomized HS patients, respectively. Small gallstones (diameter ≤5 mm) or sludge were more likely to be associated with disappearance (P = 0.04). CONCLUSIONS: Most asymptomatic gallstones grow or persist in splenectomized HS patients for an extended period. Surgical treatment of asymptomatic gallstones in HS patients requiring splenectomy is associated with a lower risk of adverse outcomes. LEVELS OF EVIDENCE: III (retrospective comparative study).

Hereditary spherocytosis before and after splenectomy and risk of hospitalization for infection.

BACKGROUND: The infectious burden in hereditary spherocytosis (HS) children before splenectomy has rarely been reported and the risk of severe postsplenectomy infection is controversial. METHODS: We conducted a retrospective study of pediatric patients with HS to evaluate the risk of infection presplenectomy and postsplenectomy. The primary outcome was any bacterial, Mycoplasma, or fungal infection that required hospitalization. The secondary outcomes were sepsis and septic shock. Appendectomized children were matched on age at surgery and enrolled as controls. RESULTS: In all, 232 patients were included. Before splenectomy, the primary outcome was identified in 51 (22.0%) patients, and the secondary outcome was identified in 1 (0.4%) patient. After splenectomy, the primary and secondary outcomes were detected in 8 (4.1%) and 1 (0.5%) patients, respectively. The risk of infection was higher presplenectomy than postsplenectomy (OR, 6.6; 95% CI, 3.0-14.2). HS patients had a higher risk of infection than the controls before surgery (OR, 3.7; 95% CI, 2.3-5.9) but not after surgery (OR, 1.4; 95% CI, 0.6-3.6). CONCLUSIONS: HS patients who require splenectomy later in life had a high incidence of hospitalization for infections. In contrast, postsplenectomy risk of hospitalization involving infection or severe infection was low. IMPACT: Patients with hereditary spherocytosis who require splenectomy later in life have a high risk of hospital admission for infections, especially those with severe hereditary spherocytosis. With vaccines or postoperative antibiotics, splenectomy does not increase the risk of infection or severe infections. Splenectomy may reduce the risk of hospitalization for infections by alleviating the complications of hereditary spherocytosis. With vaccines, prophylaxis, or advanced antibiotics, the benefits of splenectomy in children with hereditary spherocytosis and a heavy disease burden may outweigh the risks.

Immunological profile in a pediatric population of patients with spherocytosis. A single-center experience.

Spherocytosis is a hereditary disease caused by the deficiencies of different membrane proteins of red blood cells. Currently, splenectomy is the main therapeutic strategy available, although it is accompanied by an increased risk of sepsis. Several evidences have supported the hypothesis of spleen dysfunction in patients with spherocytosis that haven't yet undergone splenectomy. The aim of this study is to furtherly characterize this aspect, by describing the immune subpopulations in peripheral blood samples obtained from 41 pediatric patients with hereditary spherocytosis by flow cytometry, in order to evaluate changes in the composition of the immune populations compared to 16 healthy donors. Patients were divided in two groups: splenectomized and non-splenectomized. In the splenectomized population, data showed neutrophilic leukocytosis, thrombocytosis, increase in NK and reduction in CD4+ lymphocytes. However, we observed that most of the results obtained in the splenectomized group were found in the non-splenectomized patients as well (increase in neutrophils, in NK, reduction of CD19+, CD4+ lymphocytes and CD4+ and CD8+ naïve cells). The alterations of the immune system may be mainly due to the disease itself, regardless of splenectomy. Therefore, immunological criteria could be included in clinical phenotype assessment in order to better optimize the timing for splenectomy.

Changing trends of splenectomy in hereditary spherocytosis: The experience of a reference Centre in the last 40 years.

We describe the clinical/haematological characteristics of 446 patients with hereditary spherocytosis diagnosed in the last 40 years in a reference centre. The frequency of splenectomy decreased over time (44% before 1990 to 7% in 2011-2020), notwithstanding a confirmed good efficacy. Age at splenectomy progressively increased (63% in children before 1990 to 88% in patients aged ≥20 years in 2011-2020). Our real-life experience showed that even a fraction of patients in the trait/mild categories (19/92, 21%) were splenectomised, whilst 30/78 (38%) in the moderate/severe groups were not. Overall, these data pinpoint to the increasing awareness about post-splenectomy thromboses and infections.

Case report: A follow up of a major pelvic splenosis.

The authors present a case of a young female with extensive pelvic splenosis, which was complicated by torsion of one of the splenosis nodules operated by laparoscopy. She has been followed during several years. The diagnosis was made on the basis of the history, imaging (ultrasound, CT scan, MRI, and Technetium 99m-labeled embrittled red blood cell scans), and blood workup. The diagnosis of splenosis can be made via complications such as torsion, infarction, hemorrhage, or most often incidentally. The treatment without symptoms is abstention.

Efficacy of cytochemical tests in gene analysis of hereditary spherocytosis: a case study of six patients with different disease subtypes.

OBJECTIVES: In this study, clinical and biochemical methods were utilized to predict the final diagnosis of hereditary spherocytosis (HS), correlate the diagnosis with splenectomy, and examine the usefulness of this approach. METHODS: We biochemically and cytochemically analysed erythrocyte membrane proteins before making a final HS diagnosis based on gene analysis to compare diagnostic approaches. The clinical features of six patients with various subtypes of HS and symptoms were observed by blood analysis using eosin-5'-maleimide staining, biochemical analysis using sodium dodecyl sulphate - polyacrylamide gel electrophoresis with western blotting, and mass spectrometry. Finally, diagnostic membrane gene analysis was performed. RESULTS: Five of the six patients showed mild to moderate or severe anaemia, and the other patient was non-anaemic; all six patients showed faint eosin-5'-maleimide staining. In western blotting of erythrocyte membrane proteins, all six patients (three with ß-spectrin, two with ankyrin, and one with SLC4A1 anomalies) showed low-molecular-weight peptide fragments, which were confirmed by mass spectrometry in the region corresponding to the band 3 protein. The two patients with an ankyrin gene anomaly exhibited severe anaemia, and two patients with simultaneous SLC4A1, SPTB, and UGT1A1 anomalies exhibited mild anaemia and hyperbilirubinemia. DISCUSSION: We determined the relationship among clinical features, cytochemical parameters, and gene anomalies in six patients with newly diagnosed HS while referring to previously published cases. CONCLUSION: These findings reveal a close relationship between clinical features and membrane characteristics in HS, which can facilitate diagnosis and inform treatment.

The Successful Use of an Exchange Transfusion in a Child with Hereditary Spherocytosis Undergoing Congenital Cardiac Surgery.

Little is reported in the literature regarding hereditary spherocytosis (HS) and cardiopulmonary bypass (CPB). We present a case of a 19-month-old girl child who was referred for an atrioventricular septal defect (AVSD) and HS. The patient underwent surgical repair, and an exchange transfusion was performed at the initiation of CPB. No significant hemolysis or events attributed to HS were observed during or after CPB. The surgical repair of an AVSD in a pediatric patient with HS and total volume exchange transfusion is herein reported.

The Alexis® system for laparoscopic splenectomy in pediatric patients.

The laparoscopic splenectomy in pediatric patients is performed worldwide but often the disproportion between size of patients and size of organs requires an extra laparotomic access for spleen removal. The aim of the present study was to evaluate the safety and effectiveness of the Alexis® system to retrieve the spleen without additional laparotomic access. The charts of all patients who underwent splenectomy at our center during the last 5 years were retrieved. In all the cases the Alexis® system was placed in the umbilicus, thru which a 10 mm camera was inserted. Three additional 5 mm standard trocars were inserted. Seven patients, affected by spherocytosis (3), epidermoid cyst (2), idiopathic thrombocytopenic purpura (2) and thalassemia (1), underwent laparoscopic splenectomy at a median age of 10 years (range: 8-17). Median patients' weight was 32.5 kg (range: 25-71) and spleen size 15 cm (11-18). In all the cases, upon removal of the camera, the retrieval bag was inserted thru the umbilicus under direct view, the spleen retrieved, morcellated, and removed. No conversion nor enlargement of one of the ports nor an extra laparotomic access were required. The patients were discharged on the fifth post-operative day and the cosmetic results were excellent. Removal of the spleen can be safely performed without any additional laparotomy thru the Alexis® system placed in the umbilicus. This system is effective also in case of major patient/organ size disproportion and the final cosmetic aspect is excellent.

Laparoscopic Partial Splenectomy: A Critical Appraisal of an Emerging Technique. A Review of the First 457 Published Cases.

Background: Laparoscopic partial splenectomy (LPS) may allow avoiding total splenectomy (TS) complications and maximizing the advantages of mini-invasive approach. The objective of this review is to assess feasibility and safety of LPS, to compare this approach with alternative options. Materials and Methods: A literature review of articles reporting LPS is performed. Several parameters, including age, indication, surgical technique, devices used for splenic section/hemostasis, adverse outcomes, including morbidity/mortality, conversions to open surgery, conversions to TS, operative time (OT), and hospital stay (HS), are analyzed. Articles comparing LPS' results with those of open partial splenectomy and laparoscopic TS are also analyzed. Results: Fifty-nine articles reporting 457 LPS were included. Patients' characteristics varied widely, concerning age and indications, including hematological disease (hereditary spherocytosis, drepanocytosis), splenic focal masses, and trauma. Several technical options are reported. Mean OT and HS are 128 ± 43.7 minutes and 4.9 ± 3.8 days, respectively. No mortality and 5.7% morbidity are reported. Conversion rates to open surgery and to TS are 3.9% and 3.7%, respectively. Conclusions: In conclusion LPS is feasible and safe, with no mortality, low morbidity, and low conversion rates to laparotomy and to TS. LPS may be accomplished by various techniques and tools. Major complications are sporadically reported, thus potential risks should not be underestimated.

Partial splenectomy in children: Long-term reoperative outcomes☆.

PURPOSE: Partial, or subtotal, splenectomy (PS) has become an accepted alternative to total splenectomy (TS) for management of hematologic disorders in children, but little is known about its long-term outcomes. Here, we present our institutional experience with partial splenectomy, to determine rate of subsequent TS or cholecystectomy and identify if any factors affected this need. METHODS: All patients who underwent partial splenectomy at a single tertiary children's hospital were retrospectively reviewed from 2002 through 2019 after IRB approval. Primary outcome of interest was rate of reoperation to completion splenectomy (CS) and rate of cholecystectomy. Secondary outcome were positive predictor(s) for these subsequent procedures. RESULTS: Twenty-four patients underwent PS, at median age 6.0 years, with preoperative spleen size of 12.7 cm by ultrasound. At median follow up time of 8.0 years, 29% of all patients and 24% of hereditary spherocytosis (HS) patients underwent completion splenectomy at median 34 months and 45 months, respectively. Amongst HS patients who did not have a cholecystectomy with or prior to PS, 39% underwent a delayed cholecystectomy following PS. There were no significant differences in age at index procedure, preoperative splenic volume, weight of splenic specimen removed, transfusion requirements, preoperative or postoperative hematologic parameters (including hemoglobin, hematocrit, total bilirubin, and reticulocyte count) amongst patients of all diagnoses and HS only who underwent PS alone compared to those who went on to CS. There were no cases of OPSS or deaths. CONCLUSION: Partial splenectomy is a safe alternative to total splenectomy in children with hematologic disease with theoretical decreased susceptibility to OPSS. However, families should be counseled of a 29% chance of reoperation to completion splenectomy, and, in HS patients, a 39% chance of delayed cholecystectomy if not performed prior to or with PS. Further studies are needed to understand predictors of these outcomes.

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.

Open heart surgery in an infant with hereditary spherocytosis and a review of literature.

Hemolytic anemia often challenges congenital heart surgery. Hereditary spherocytosis is a rare familial hemolytic anemia. When associated with congenital heart disease, the safe performance of cardiopulmonary bypass becomes a priority. The increased risk of hemolysis during cardiopulmonary bypass could potentially lead to significant secondary organ damage. Till now, only very few reports of successful repair of a congenital heart defect in patients with hereditary spherocytosis have been reported. We report the only case of successful repair of a congenital heart defect in an infant with hereditary spherocytosis.