Laparoscopic splenectomy: how minimal can we make it?

Aims Laparoscopic splenectomy (LS) is routinely performed in children, however, a large spleen in a small child can pose significant operative challenges. We instigated a highly standardised surgical and anaesthetic approach to LS to minimise surgical trauma and enhance recovery. The aim of this study was to assess the outcomes of this programme. Methods Prospective study of all LS’s performed 2018–2021. Surgical approach was via one 10 mm and three 5 mm ports. Early hilar control was accomplished with Hem-o-loks. Splenic retrieval via the 10 mm incision used finger morcellation within an Espiner EcoSac. Anaesthesia utilised a standardised regime of agents and bupivacaine was infiltrated to the splenic bed and wound sites. Post-operative opiates were minimised. Data are presented as median [IQR]. Results Twenty consecutive children were included. Indications for LS were hereditary spherocytosis (n = 12), sickle cell disease (n = 6), beta-thalassaemia (n = 1) and splenic haemangiomatosis (n = 1). Age at surgery was 101 months [75–117] and weight 30 kg [21–37]. Splenic size was 13.4 cm [12–14.4]. Operative time was 178 min [156–185]. There were no open conversions and no significant intra or post-operative bleeding. One patient developed pancreatitis. Median post-operative pain score was 1 [1–3]. Median length of stay was 2 days [2–3]. Conclusion LS is feasible, safe and efficient in smaller children with large spleens. This standardised programme of anaesthesia and surgery based around a core team reliably results in few complications, good analgesia and short length of stay.

Clinical and genetic diagnosis of thirteen Japanese patients with hereditary spherocytosis

Hereditary spherocytosis is the most frequent cause of hereditary hemolytic anemia and is classified into five subtypes (SPH1-5) according to OMIM. Because the clinical and laboratory features of patients with SPH1-5 are variable, it is difficult to classify these patients into the five subtypes based only on these features. We performed target capture sequencing in 51 patients with hemolytic anemia associated with/without morphological abnormalities in red blood cells. Thirteen variants were identified in five hereditary spherocytosis-related genes (six in ANK1 [SPH1]; four in SPTB [SPH2]; and one in each of SPTA1 [SPH3], SLC4A1 [SPH4], and EPB42 [SPH5]). Among these variants, seven were novel. The distribution pattern of the variants was different from that reported previously in Japan but similar to those reported in other Asian countries. Comprehensive genomic analysis would be useful and recommended, especially for patients without a detailed family history and those receiving frequent blood transfusions due to chronic hemolytic anemia.

Title: Malnutrition from anorexia nervosa triggers severe complications of hereditary spherocytosis in an adolescent girl: A case report. Running Title: Anorexia Nervosa causes complications of hemoglobinopathy

Hemolytic crises and aplastic crises in hereditary spherocytosis (HS) are typically triggered by viral infections. We present the case of an adolescent with HS who developed unexpected and life threatening consequences of her hemoglobinopathy as a consequence of anorexia nervosa and severe malnutrition.

Role of Surgical Intervention in Hereditary Spherocytosis with Haemolytic Anaemia, Splenomegaly and Jaundice

haemolytic anaemia, splenomegaly and jaundice, admitted in Chettinad hospital and research institute during one year period from January 2019 to January 2020. Surgical intervention is indicated for selected patients with hereditary spherocytosis with haemolytic anaemia and jaundice to abate the hemolytic process after correction of anaemia with blood transfusion. Pigmented gallstones are seen in more than 50% cases for which incidence increases with severity of hemolysis and with age. Complications include aplastic anemia (most common after parvovirus B19 infection), haemolytic crisis during inter-current infection, megaloblastic crisis – during folic acid deficiency, cardiomyopathy, hematological malignancies.

Bursting the bubble: hereditary spherocytosis masking poor glycemic control

Hemoglobin A1c (HbA1c) is a very common measure utilized to diagnose diabetes and to monitor the level of glycemic control during the course of management. Despite the high utility of HbA1c, it has some limitations. Physiological conditions that affect the lifespan of red blood cells (RBCs) can falsely elevate or lower HbA1c results. In this case report, we present a case of a patient who was found to have hereditary spherocytosis (HS) after developing nephrotic range proteinuria. The patient had diabetes that was previously thought to be well controlled, but his HS was masking his poor glycemic control. This case highlights the importance of understanding the limitations of the HbA1c in managing patients with diabetes.

Genetic Spectrum of Inherited/Congenital Hemolytic Anemias in Indian Patients

Introduction Hemolytic anemias are a group of disorders caused by the premature destruction of red blood cells with reticulocytosis. Common causes of inherited/congenital hemolysis are hemoglobinopathies and thalassemia syndromes, red blood cell membrane, and enzyme disorders. Most of the common causes (thalassemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis, etc.) are diagnosed based on laboratory testing; however, for remaining causes laboratory tests are either inaccessible or cumbersome. We follow a stepwise diagnostic pipeline and red cell morphology is helpful with membrane disorders. Phenotypes vary from severe hemolysis (transfusion-dependent) to mild/asymptomatic patients. Undiagnosed haemolytic anemias are taken up for multi-gene panel-based targeted resequencing which is rapid, accurate, and cost-effective. The use of these panels expedites the diagnoses of inherited hemolytic anemias and is eventually helpful for evidence-based genetic counseling. Objectives This study aimed to determine the genetic defects in inherited/congenital hemolytic anemias which remained unexplained after routine laboratory tests. Methods Seventy-five families were enrolled based on the clinical and laboratory features of inherited/congenital hemolytic anemias. Common causes of inherited hemolysis are G6PD deficiency, hemoglobinopathies and thalassemia syndromes, autoimmune hemolytic anemias, hereditary spherocytosis, and pyruvate kinase (PK) deficiency were excluded on the basis of biochemical and molecular tests. DNA extraction was done QIAamp DNA Blood Mini Kit. Quantity and quality of DNA were verified using NanoDrop and Qubit Fluorometer respectively. DNA libraries were prepared using Amplicon custom panels for genes implicated in hemolytic anemias and sequenced on Illumina MiSeq Sequencer. Alignment and variant calling were done in Illumina Local run Manager and Variant annotation was done in Basespace VariantInterpretor. Sanger sequencing was done as orthogonal validation in the index case. Predictive testing was performed for the family members. Results After targeted resequencing of the total 75 index cases, 19 patients were found to have red blood cell enzymopathies, 15 patients had stomatocytosis, 13 had membranopathies and three patients had unstable hemoglobins. In 8 patients cause was not established either only heterozygous variant was found for autosomal recessive or due to the lack of samples of family members for screening. Seventeen cases remained unexplained even after next-generation sequencing. Out of 19 patients, unexpected PK deficiency was found in 12 patients and G6PD deficiency was found in 3 patients; despite the enzyme assay being normal in these cases. We also found 2 patients with glucose-6-phosphate isomerase deficiency. One case each with hexokinase deficiency and glutathione synthetase deficiency was found. Among 15 patients with stomatocytosis, 8 had Mediterranean stomatocytosis/macrothrombocytopenia (ABCG5/ABCG8). These 8 patients showed the presence of stomatocytosis along with giant platelets on peripheral smear evaluation. Of the remaining 7 cases , 2 were found to have overhydrated hereditary stomatocytosis (RHAG) and dehydrated Stomatocytosis/xerocytosis was found in 5 (PIEZO1/KCNN4). We also found 13 cases of hemolytic anemia to have a genetic defect in red blood cell membrane protein-coding genes. Of these 5 had probably pathogenic variants in the ANK1 gene, 5 had a pathogenic variant in SPTA1, 2 had SPTB 2, and 1 patient SLC4A1. We also encountered 3 cases of unstable hemoglobins where no abnormality was noted in Hb-HPLC patterns. A total of seven patients underwent splenectomy and are transfusion free. Conclusions Our cohort of 75 families of hemolytic anemia of unexplained etiology showed a highly heterogeneous genetic spectrum. Of the total cases, the confirmed diagnosis was achieved in 67% of the patients. This approach of using a multi-gene panel is cost-effective and can provide a rapid and accurate diagnosis. Unexpected PK deficiency, G6PD deficiency, and unstable hemoglobins suggest that such cases can be missed. Providing accurate diagnosis in such cases provides evidence-based counseling and saves the families from inappropriate treatments. Disclosures No relevant conflicts of interest to declare.