Paeds · haematology-oncology-and-transfusion
Hereditary spherocytosis and membrane disorders
Also known as Hereditary spherocytosis · HS · Hereditary elliptocytosis · Hereditary pyropoikilocytosis · Hereditary stomatocytosis · Red cell membrane disorders
Fellowship guide to hereditary spherocytosis and the inherited red cell membrane disorders: the pale jaundiced child with splenomegaly, the spherocyte on the blood film, the eosin-5-maleimide binding test, the severity spectrum from compensated to transfusion-dependent, folate supplementation and transfusion support, splenectomy timing and technique (total versus partial), the pre-splenectomy vaccination and post-splenectomy antibiotic prophylaxis bundle, the post-splenectomy sepsis risk, and the membrane disorders that must not be splenectomised (hereditary stomatocytosis).
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- A child with hereditary spherocytosis who develops sudden pallor with reticulocytopenia has a parvovirus B19 aplastic crisis — transfuse urgently and isolate, because the haemoglobin can fall to life-threatening levels within days
- Splenectomy is the only curative treatment for the haemolysis of hereditary spherocytosis, but it converts a child to an asplenic host with a lifelong risk of overwhelming post-splenectomy infection — complete the vaccination bundle and antibiotic prophylaxis before and after surgery, and defer splenectomy until at least six years where possible
- Hereditary stomatocytosis must be distinguished from hereditary spherocytosis before any splenectomy, because splenectomy in stomatocytosis carries a high risk of fatal thromboembolism — check the blood film and the EMA binding test carefully
- A neonate with early-onset or prolonged jaundice and a falling haemoglobin may have hereditary spherocytosis — investigate aggressively, because undiagnosed severe HS can cause bilirubin encephalopathy and require exchange transfusion
- Any splenectomised child who presents with fever is having overwhelming post-splenectomy infection until proven otherwise — give parenteral antibiotics immediately without waiting for investigation results
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- Haematology
- Inherited haemolytic anaemia
- Hereditary spherocytosis
- Paediatric Haematology — hereditary spherocytosis and membrane disorders
- General Paediatrics learning goal — recognise and manage hereditary spherocytosis
- Pre-splenectomy vaccination and post-splenectomy prophylaxis bundle
- Clinical Applications
- Haemolytic anaemia
- Long Cases
- Short Cases
- Communication scenarios
- Haematology and oncology: recognises and manages hereditary spherocytosis
- Safe splenectomy pathway and asplenic precautions
- Foundation of Practice (FOP)
- Applied Knowledge in Practice (AKP)
- Hereditary spherocytosis and membrane disorders
- Clinical
- History
- Communication
- Abdominal examination
- General Pediatrics Content Outline — Domain: Haematology
- Subspecialty: Pediatric Hematology — inherited haemolytic anaemia
- Patient Care 1: History and Physical Examination
- Patient Care 4: Clinical Reasoning
- Medical Knowledge 1: Clinical Knowledge of hereditary spherocytosis
- Systems-Based Practice 1: multidisciplinary haematology and surgical care
- Medical Expert
- Collaborator
- Pediatrics: Core EPA — recognise and manage inherited haemolytic anaemia
Overview & Definition
Picture the six-year-old who has always been a little pale and yellow, sent to you because the teacher noticed she tires easily, and whose blood film shows small dense round cells without central pallor scattered among otherwise normal red cells. Her mother had her gallbladder out at twenty-five and her grandmother was always told she had a fragile blood condition. That family story is hereditary spherocytosis, and the blood film has just handed you the diagnosis. [1]
Hereditary spherocytosis is a group of inherited disorders of the red blood cell membrane in which a quantitative or qualitative deficiency of one or more membrane skeleton proteins destabilises the vertical interactions that tether the lipid bilayer to the underlying spectrin-based cytoskeleton. The membrane blebs off in small fragments, the cell loses surface area without losing volume, and the resulting decrease in the surface-to-volume ratio forces the biconcave disc into a sphere. The spherocyte is rigid and lacks the deformability to pass through the splenic cords, so it is trapped and destroyed by splenic macrophages — the extravascular haemolysis that defines the clinical picture. [1] [4]
The inherited red cell membrane disorders form a family defined by which protein interaction is defective and what shape the cell takes. Hereditary spherocytosis, the commonest and most examinable, is a vertical interaction defect producing spherocytes. Hereditary elliptocytosis is a horizontal skeleton defect producing elliptocytes, usually mild or asymptomatic. Hereditary pyropoikilocytosis is the severe neonatal form. Hereditary stomatocytosis is a cation-leak disorder producing stomatocytes, and it carries the critical caveat that splenectomy is dangerous. Together these disorders share the themes of inherited haemolysis, membrane morphology on the blood film, and splenic destruction — but they diverge sharply in management, which is why distinguishing them matters enormously. [3] [4]
References10ShowHide
- [1]Perrotta S, Gallagher PG, Mohandas N Hereditary spherocytosis. Lancet, 2008.PMID 18940465
- [2]Bolton-Maggs PH, Langer JC, Iolascon A, Tittensor P, King MJ Guidelines for the diagnosis and management of hereditary spherocytosis--2011 update. Br J Haematol, 2012.PMID 22055020
- [3]Da Costa L, Galimand J, Fenneteau O, et al. Hereditary spherocytosis, elliptocytosis, and other red cell membrane disorders. Blood Rev, 2013.PMID 23664421
- [4]Gallagher PG Abnormalities of the erythrocyte membrane. Pediatr Clin North Am, 2013.PMID 24237975
- [5]Christensen RD, Yaish HM, Gallagher PG A pediatrician's practical guide to diagnosing and treating hereditary spherocytosis in neonates. Pediatrics, 2015.PMID 26009624
- [6]Iolascon A, Andolfo I, Russo R Advances in understanding the pathogenesis of red cell membrane disorders. Br J Haematol, 2019.PMID 31364155
- [7]Andolfo I, Russo R, Gambale A, et al. Hereditary stomatocytosis: An underdiagnosed condition. Am J Hematol, 2018.PMID 28971506
- [8]Casale M, Perrotta S Splenectomy for hereditary spherocytosis: complete, partial or not at all? Expert Rev Hematol, 2011.PMID 22077527
- [9]Tang X, Xue J, Zhang J, et al. The efficacy of partial versus total splenectomy in the treatment of hereditary spherocytosis in children: a systematic review and meta-analysis. Pediatr Surg Int, 2024.PMID 39470805
- [10]Liu Y, Jin S, Xu R, et al. Hereditary spherocytosis before and after splenectomy and risk of hospitalization for infection. Pediatr Res, 2023.PMID 35915237