Hereditary Spherocytosis

Table of Contents

  1. What is Hereditary Spherocytosis?
  2. Genetics and Inheritance Patterns
  3. Pathophysiology: Membrane Defects and Spherocyte Formation
  4. Clinical Presentation: The Classic Triad
  5. Aplastic Crisis and Parvovirus B19
  6. Diagnosis: Smear, EMA Binding, and Coombs Test
  7. Laboratory Findings and Distinguishing Features
  8. Treatment: Folate, Splenectomy, and Vaccination
  9. Splenectomy: Indications, Risks, and Timing
  10. Long-Term Outcomes and Monitoring
  11. Research Papers
  12. Connections
  13. Featured Videos

What is Hereditary Spherocytosis?

Hereditary spherocytosis (HS) is the most common inherited red blood cell (RBC) membrane disorder in individuals of Northern European ancestry, affecting approximately 1 in 2,000 people in that population. It is characterized by a defect in the proteins that anchor the red blood cell's outer lipid bilayer to its internal cytoskeletal network, causing the cells to lose their normal biconcave disc shape and adopt a spherical form — the defining spherocyte. These misshapen, rigid spherocytes cannot deform adequately to squeeze through the narrow sinusoids of the spleen, where they are trapped and destroyed, leading to hemolytic anemia, jaundice, and splenomegaly.

Unlike many hereditary anemias that are concentrated in malaria-endemic regions, hereditary spherocytosis is found predominantly in Northern and Central European populations, consistent with a founder effect rather than a malaria-protective advantage. The disorder spans a wide clinical spectrum — from a mild, well-compensated anemia that may not be diagnosed until adulthood, to a severe hemolytic anemia requiring early transfusion support in infancy. Most patients fall in the mild-to-moderate range and can lead normal lives with appropriate monitoring and, when needed, surgical intervention.

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Genetics and Inheritance Patterns

Hereditary spherocytosis arises from mutations in genes encoding key red cell membrane-cytoskeleton anchor proteins. Understanding which protein is affected helps predict disease severity and guides genetic counseling.

Autosomal Dominant Inheritance (75% of Cases)

The majority of hereditary spherocytosis cases follow an autosomal dominant inheritance pattern, meaning a single mutant allele from one parent is sufficient to cause disease. The affected genes include:

Autosomal Recessive Inheritance (25% of Cases)

Approximately 25% of HS cases follow an autosomal recessive pattern, requiring two mutant alleles (homozygous or compound heterozygous). Autosomal recessive HS tends to be more clinically severe, as both alleles of the affected gene are non-functional:

De Novo Mutations

Approximately 25% of HS cases represent new (de novo) mutations, occurring in patients with no family history of the disorder. This fraction is particularly relevant when evaluating an infant or child with unexplained hemolytic anemia and negative family history — hereditary spherocytosis should still be considered even without an affected parent.

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Pathophysiology: Membrane Defects and Spherocyte Formation

The red blood cell's ability to survive its 120-day lifespan while repeatedly deforming to pass through capillaries narrower than the cell itself depends on the structural integrity of its membrane skeleton. In hereditary spherocytosis, defects in this skeleton disrupt the vertical connections between the lipid bilayer and the underlying cytoskeleton, leading to progressive membrane loss and spherocyte formation.

The Normal Red Cell Membrane Architecture

The red cell membrane is a bilayer lipid membrane supported by a two-dimensional cytoskeletal network on its inner surface. The cytoskeleton is composed primarily of spectrin heterodimers (alpha-spectrin + beta-spectrin) that associate into tetramers, cross-linked by short actin filaments and protein 4.1 into a hexagonal lattice. This lattice is tethered to the lipid bilayer through two types of vertical connections:

The result is a membrane that is simultaneously strong (cytoskeleton resists deformation) and flexible (lipid bilayer can deform). This combination allows normal biconcave RBCs to squeeze through capillaries as narrow as 3 micrometers.

Membrane Vesiculation: How Spherocytes Form

In hereditary spherocytosis, mutations in ankyrin, spectrin, band 3, or protein 4.2 weaken the vertical connections between cytoskeleton and lipid bilayer. This weakness causes the outer lipid bilayer to spontaneously vesiculate — small lipid blebs pinch off from unsupported areas of the membrane and are released into the circulation. With each pass through the circulation, the cell loses surface area through membrane vesiculation while its internal volume remains relatively constant. The result is a progressive increase in the surface area-to-volume ratio imbalance: the cell becomes more spherical as it loses membrane, ultimately forming the classic spherocyte — a round, dense, small cell with no central pallor.

Splenic Trapping and Destruction

The spleen is the primary site of spherocyte destruction. Normal red cells easily pass through the narrow interendothelial slits of the splenic sinusoids (2–3 µm diameter, smaller than the 8 µm diameter of a normal RBC), deforming their flexible biconcave disc shape to squeeze through. Spherocytes, having lost surface area relative to volume and being more rigid, cannot deform adequately. They become entrapped in the splenic red pulp cords and sinusoids, where macrophages recognize and phagocytose them — this is extravascular hemolysis. The spleen also worsens spherocyte formation by exposing trapped cells to acidic, glucose-deprived, oxidatively stressed conditions that accelerate membrane vesiculation. Splenectomy, therefore, removes the primary destruction site and dramatically improves anemia even though spherocytes remain present on the blood smear after surgery.

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Clinical Presentation: The Classic Triad

The classic clinical triad of hereditary spherocytosis — anemia, jaundice, and splenomegaly — reflects the consequences of chronic extravascular hemolysis. The severity of each component correlates with the degree of hemolysis, which in turn reflects the severity of the underlying membrane defect.

Anemia

Anemia in HS ranges from fully compensated (hemoglobin within normal range due to adequate erythropoietic compensation) to moderately severe (hemoglobin 8–11 g/dL), with rare severe cases requiring transfusion. Most patients with mild-to-moderate HS have chronic, stable anemia with reticulocytosis reflecting the bone marrow's compensatory increased red cell production. Fatigue, pallor, reduced exercise tolerance, and exertional dyspnea are the dominant symptoms. Many patients with mild HS are not diagnosed until adulthood, when routine blood work reveals unexplained mild anemia with an elevated MCHC (mean corpuscular hemoglobin concentration) — a laboratory finding that is virtually unique to HS among the hemolytic anemias.

Jaundice

Jaundice in HS is caused by the overproduction of unconjugated (indirect) bilirubin from hemoglobin released during red cell destruction. The liver conjugates bilirubin and excretes it into bile, but when hemolysis exceeds hepatic conjugating capacity, indirect bilirubin accumulates in the blood, causing scleral icterus and skin jaundice. In HS, jaundice is typically low-grade and chronic, often described as a faint yellow tinge of the sclerae rather than the deep yellow jaundice of hepatic or biliary disease. Parents of infants with HS often report persistent neonatal jaundice extending beyond the usual 2 weeks. Episodic worsening of jaundice — particularly during intercurrent viral illnesses — reflects transient increases in hemolysis.

Splenomegaly

Splenomegaly — an enlarged spleen palpable on abdominal examination — is present in the majority of patients with HS. The spleen enlarges because it is overworking: increased reticuloendothelial activity from constant trapping and phagocytosis of spherocytes drives splenic hyperplasia. In severe HS, the spleen can become massive, causing left upper quadrant discomfort, early satiety, and occasionally hypersplenism (exacerbating the anemia through sequestration). The enlarged spleen is also at risk for traumatic rupture in contact sports or accidents, a consideration in management decisions about activity restriction and splenectomy timing.

Pigment Gallstones

A major long-term complication of chronic hemolysis in HS is the formation of pigment gallstones (bilirubin gallstones). Excess bilirubin secreted into bile precipitates as calcium bilirubinate, forming black pigment stones in the gallbladder. The cumulative incidence of gallstones in HS is substantial: approximately 20–30% of adolescents and 50% or more of adults with untreated moderate-to-severe HS develop cholelithiasis. Gallstones can cause biliary colic, cholecystitis, choledocholithiasis, and cholangitis. When symptomatic cholelithiasis develops in a patient already requiring splenectomy for HS, laparoscopic cholecystectomy is typically performed simultaneously, avoiding a second operation.

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Aplastic Crisis and Parvovirus B19

Among the most dangerous acute complications of hereditary spherocytosis is the aplastic crisis — a temporary but profound suppression of red blood cell production triggered by parvovirus B19 infection. Understanding this complication is critical because it is potentially life-threatening and requires immediate recognition and management.

Parvovirus B19: Mechanism of Red Cell Aplasia

Parvovirus B19 is a small, non-enveloped DNA virus that has a specific tropism for human erythroid progenitor cells in the bone marrow. The virus binds to the P blood group antigen (globoside) expressed on the surface of erythroid progenitors and early erythroblasts, enters the cell, and replicates, causing apoptosis and destruction of the progenitor population. In immunologically normal individuals without chronic hemolysis, transient red cell aplasia lasting 7–10 days is clinically silent because normal red cells survive for 120 days — the brief production pause barely affects the peripheral red cell count.

In patients with hereditary spherocytosis, the situation is dramatically different. Because spherocytes are continuously destroyed at an accelerated rate, the HS patient's red cell survival is only 10–20 days (versus the normal 120 days). The bone marrow must produce red cells at 5–10 times the normal rate to maintain hemoglobin levels. When parvovirus B19 abruptly shuts down this high-rate erythropoiesis, red cell counts fall precipitously within days to a week. The hemoglobin can drop to 2–4 g/dL, levels causing hemodynamic compromise, congestive heart failure, and cardiovascular collapse.

Clinical Recognition of Aplastic Crisis

The aplastic crisis presents as an acute, severe worsening of anemia in a patient with known HS (or sometimes as the first presentation of previously undiagnosed HS). Characteristic features that distinguish aplastic crisis from a simple hemolytic exacerbation:

Treatment and Family Considerations

Aplastic crisis is managed with red blood cell transfusion to maintain adequate hemoglobin while the bone marrow recovers. Recovery of erythropoiesis typically occurs within 1–2 weeks as the immune system clears parvovirus B19 infection, producing IgM then IgG anti-parvovirus antibodies. Immunity after infection is lifelong in immunocompetent individuals. Because parvovirus B19 is highly contagious, an aplastic crisis in one family member with HS should prompt evaluation of siblings and parents with HS, who may simultaneously develop aplastic crises. Pregnant women in the household without prior immunity to parvovirus B19 should avoid exposure (parvovirus can cause hydrops fetalis in the fetus of a susceptible pregnant woman). No antiviral therapy is available for acute parvovirus B19 infection in immunocompetent hosts; IVIG can be used in chronic infection in immunocompromised patients.

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Diagnosis: Smear, EMA Binding, and Coombs Test

The diagnosis of hereditary spherocytosis rests on the combination of clinical features (family history, hemolytic anemia, jaundice, splenomegaly), peripheral blood smear findings, and confirmatory laboratory tests. The diagnostic approach has evolved significantly over the past two decades, with the EMA binding test replacing the older osmotic fragility test as the preferred confirmatory test.

Peripheral Blood Smear: The Spherocyte

The peripheral blood smear is the first and most important diagnostic test. In HS, the smear shows spherocytes — small, round, densely stained red cells that lack the central pallor of normal biconcave red cells. A normal red blood cell has a central area of pallor (lighter staining) occupying approximately one-third of the cell's diameter, reflecting the biconcave disc's thinner central region. Spherocytes have lost this central pallor entirely; they appear as uniformly dense, deeply stained, round cells that are typically smaller than normal red cells (microspherocytes).

The percentage of spherocytes on the smear roughly correlates with disease severity. It is important to note that spherocytes are not pathognomonic for HS — they also appear in autoimmune hemolytic anemia (AIHA), ABO incompatibility (in neonates), severe thermal burns, and occasionally other conditions. The clinical context and additional testing distinguish these entities. Importantly, the direct antiglobulin test (Coombs test) is negative in HS, differentiating it from AIHA where antibody-mediated destruction is the mechanism.

Eosin-5-Maleimide (EMA) Binding Test

The eosin-5-maleimide (EMA) binding test is now considered the first-line confirmatory test for hereditary spherocytosis. EMA is a fluorescent dye that covalently binds to lysine residues on band 3 protein (and also to band 4.2 and Rh-related proteins) on the red cell surface. The amount of EMA fluorescence measured by flow cytometry directly reflects the quantity of band 3 protein present per red cell.

In HS, because band 3 protein is either directly mutated (band 3 deficiency) or secondarily reduced through loss of membrane surface (band 3 leaves the membrane as the bilayer vesiculates), EMA fluorescence is reduced — typically 15–30% below the normal range. The EMA binding test has both high sensitivity (approximately 93%) and high specificity (approximately 99%) for HS, making it far superior to the osmotic fragility test, which it has largely replaced. A negative EMA binding test (normal or elevated EMA fluorescence) argues strongly against the diagnosis of hereditary spherocytosis.

Direct Antiglobulin Test (DAT / Coombs Test)

The direct antiglobulin test is a crucial part of the diagnostic workup for hereditary spherocytosis, not to diagnose HS directly, but to exclude autoimmune hemolytic anemia (AIHA) as the cause of spherocytosis and hemolysis. In AIHA, the DAT is positive — IgG antibodies (warm AIHA) or complement C3d (cold AIHA) are detected on the red cell surface. In HS, the DAT is negative. This distinction is critical because the treatments are completely different: AIHA is treated with immunosuppression (corticosteroids, rituximab), while HS is managed with folate supplementation, splenectomy, and vaccination. A positive DAT in a patient with apparent spherocytosis should redirect the diagnosis toward AIHA.

Historical Tests Now Largely Replaced

The osmotic fragility test — measuring the osmolarity at which red cells lyse — was historically the standard confirmatory test for HS. Spherocytes, having less membrane reserve, lyse at higher osmolarity (lower NaCl concentration) than normal red cells. While the osmotic fragility test can confirm HS, it is less sensitive than EMA binding (approximately 68% sensitivity), can be normal in mild HS, and requires special handling. It has been largely superseded by EMA binding in centers with flow cytometry capacity. The cryohemolysis test — measuring hemolysis after brief heating to 37°C then cooling — is another alternative with good sensitivity but similar limitations. Genetic testing can definitively confirm the diagnosis and identify the specific mutation, but is typically reserved for cases with atypical presentations or when family genetic counseling is specifically requested.

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Laboratory Findings and Distinguishing Features

Several laboratory findings in hereditary spherocytosis are characteristic enough to guide diagnosis even before confirmatory testing is performed.

Elevated MCHC: The Most Specific Screening Marker

The mean corpuscular hemoglobin concentration (MCHC) — a measure of the hemoglobin concentration per unit volume of red cells — is elevated in HS, typically above 36 g/dL (normal: 32–36 g/dL). This elevation reflects the abnormally dense, dehydrated nature of spherocytes: the cells have lost surface area (membrane) but retained their hemoglobin content, so the hemoglobin concentration per cell volume is increased. An elevated MCHC is not specific for HS alone, but among all hemolytic anemias, HS consistently produces the highest MCHC values. An MCHC above 36 g/dL in a patient with hemolytic anemia should prompt immediate consideration of HS and EMA binding testing.

Elevated RDW and Reticulocytosis

The red cell distribution width (RDW) is elevated in HS, reflecting the coexistence of small, dense microspherocytes and large reticulocytes (young red cells released by the hyperactive bone marrow). The reticulocyte count is elevated (reticulocytosis) — typically 5–20% in moderate HS — as the bone marrow compensates for accelerated destruction. During aplastic crisis, the reticulocyte count drops precipitously to near zero, a key diagnostic clue.

Hemolysis Markers

The standard markers of hemolysis are present in HS:

Neonatal Presentation

Hereditary spherocytosis often presents in the neonatal period with prolonged indirect hyperbilirubinemia (neonatal jaundice) requiring phototherapy or, rarely, exchange transfusion. The combination of neonatal jaundice with a positive family history of anemia, jaundice, gallstones, or splenectomy should prompt a smear and EMA binding test. ABO incompatibility (which can also cause neonatal spherocytosis and jaundice) is distinguished from HS by the positive DAT in ABO incompatibility and the maternal blood type.

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Treatment: Folate, Splenectomy, and Vaccination

The management of hereditary spherocytosis is tailored to disease severity. Most patients with mild HS require only folate supplementation and periodic monitoring. Those with moderate-to-severe HS may benefit from splenectomy, with careful attention to timing and infectious prophylaxis.

Folic Acid Supplementation

Folic acid (vitamin B9) supplementation is recommended for all patients with moderate-to-severe HS and considered for mild HS. The rationale is straightforward: chronic hemolysis dramatically increases the rate of red cell production, which proportionally increases the demand for folate (required for DNA synthesis in erythroid progenitors). When folate demand chronically exceeds dietary intake, megaloblastic anemia superimposes on the underlying hemolytic anemia — a preventable complication called megaloblastic crisis. Standard dosing is folic acid 1–5 mg/day orally. This is particularly important in pregnant women with HS, who have increased folate requirements both from hemolysis and from fetal development.

Blood Transfusion in Acute Settings

Red blood cell transfusion is the primary treatment for acute, severe anemia in HS — most commonly during aplastic crises triggered by parvovirus B19, and occasionally during severe hemolytic exacerbations in the setting of intercurrent infections. Transfusion thresholds in HS follow general principles: transfuse for hemoglobin below 7–8 g/dL in symptomatic patients, or higher thresholds in patients with cardiorespiratory compromise. Patients with severe HS may require chronic transfusion support before splenectomy is performed at an appropriate age. Leukoreduced, irradiated, and if needed phenotype-matched blood products are used to minimize alloimmunization risk in transfusion-dependent patients.

Management of Gallstones

Surveillance with abdominal ultrasound is recommended to monitor for gallstone formation, particularly in adolescents and adults with moderate-to-severe HS who have not undergone splenectomy (which reduces bilirubin overproduction and thereby decreases gallstone risk). When symptomatic cholelithiasis develops (biliary colic, cholecystitis), laparoscopic cholecystectomy is indicated. In patients also meeting criteria for splenectomy, both procedures are ideally performed simultaneously to avoid two separate operations and their associated anesthetic and infectious risks.

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Splenectomy: Indications, Risks, and Timing

Splenectomy — surgical removal of the spleen — is the most effective treatment for hereditary spherocytosis. By removing the organ responsible for trapping and destroying spherocytes, splenectomy eliminates the primary site of hemolysis and dramatically improves anemia in nearly all patients. However, splenectomy carries lifelong infectious risks that require careful consideration, particularly in children.

How Splenectomy Works (and Its Limits)

After splenectomy, spherocytes continue to form and circulate — the underlying membrane defect persists, and spherocytes remain visible on the peripheral blood smear for the patient's lifetime. What changes is that spherocytes are no longer trapped in splenic sinusoids and destroyed. The freed spherocytes, despite being less deformable than normal red cells, can survive in the circulation for a substantially longer time. Hemolysis decreases, reticulocyte count falls, and hemoglobin rises, typically to near-normal or normal levels. Most patients with moderate-to-severe HS achieve complete or near-complete normalization of hemoglobin after splenectomy. Bilirubin levels fall as well, reducing the risk of further pigment gallstone formation.

Indications for Splenectomy

Splenectomy is indicated for:

Splenectomy is generally not recommended for mild HS with adequate hemoglobin compensation. The lifelong infectious risks of splenectomy outweigh the benefit when anemia is mild. Observation with folate supplementation is appropriate for most mild HS patients.

Timing: Why to Wait in Children

The spleen plays a critical role in the immune response, particularly against encapsulated bacteria — organisms with polysaccharide capsules that evade phagocytosis and require opsonization via antibodies or complement to be cleared. The key pathogens are Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b. After splenectomy, patients are at lifelong increased risk of rapidly fatal overwhelming post-splenectomy infection (OPSI) — a sepsis syndrome that can progress from initial fever to cardiovascular collapse and death within 12–24 hours from these encapsulated organisms.

In children, the spleen's immunologic role is particularly important. Splenectomy in children under 5 years of age carries a substantially higher risk of OPSI (estimated 1–2% annual risk in young children) compared to adults. Current guidelines therefore recommend deferring splenectomy until age 5–6 years at the earliest in most patients, and until age 12+ in mild-to-moderate cases where the delay is medically acceptable. This delay allows sufficient maturation of the humoral immune system so that asplenic patients can mount better antibody responses.

Laparoscopic splenectomy (minimally invasive) is now the standard surgical approach, offering shorter hospitalization and recovery compared to open splenectomy. Partial splenectomy — removing only part of the spleen to reduce hemolysis while preserving some splenic immune function — is an option in young children who require early intervention, though residual splenic tissue can hypertrophy and hemolysis may recur over time.

Pre-Splenectomy Vaccination: Mandatory

Before splenectomy, patients must receive vaccinations against the encapsulated bacteria responsible for OPSI. Vaccines should be administered at least 2 weeks before surgery to allow adequate immune response before the spleen is removed:

Post-splenectomy, vaccination schedules require periodic boosting, particularly for pneumococcal and meningococcal vaccines. Children undergoing splenectomy before age 5 typically receive penicillin prophylaxis (oral amoxicillin or penicillin V) daily until at least age 18 to reduce OPSI risk during the years of greatest susceptibility. Adults may be given an emergency antibiotic supply (amoxicillin or amoxicillin-clavulanate) to take at the first sign of fever, with instructions to seek immediate medical care.

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Long-Term Outcomes and Monitoring

With appropriate management, patients with hereditary spherocytosis lead normal lifespans. The goals of long-term management are preventing complications (aplastic crisis, gallstones, megaloblastic anemia), monitoring for disease progression, and ensuring lifelong infectious prophylaxis in asplenic patients.

Mild HS: Observation and Monitoring

Most patients with mild HS managed without splenectomy require periodic monitoring of hemoglobin, reticulocyte count, bilirubin, and abdominal ultrasound for gallstone surveillance. The primary concern is the development of symptomatic gallstones and, less commonly, aplastic or megaloblastic crises. Folic acid supplementation continues lifelong. Activity restriction is generally not required, though contact sport participation should be discussed given the risk of traumatic splenic rupture in the setting of significant splenomegaly.

After Splenectomy: Lifelong Infection Vigilance

The most important long-term management task after splenectomy is infectious risk management. Asplenic patients must:

Genetic Counseling

Families with hereditary spherocytosis should be offered genetic counseling, particularly in planning pregnancies. For autosomal dominant HS, each child of an affected parent has a 50% chance of inheriting the mutation. Prenatal testing is possible for families where the specific mutation has been identified. Neonatal screening of at-risk infants (positive family history) with peripheral blood smear and EMA binding testing shortly after birth allows early detection and preparation for managing neonatal jaundice and aplastic crisis risk. Siblings of affected children should be evaluated for subclinical HS even if they appear clinically normal.

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Research Papers

  1. Gallagher PG. Hereditary elliptocytosis: spectrin and protein 4.1R. Semin Hematol. 2004;41(2):142–164. PMID: 15071790
  2. Eber SW, Armbrust R, Schröter W. Variable clinical severity of hereditary spherocytosis: relation to erythrocytic spectrin concentration, osmotic fragility, and autohemolysis. J Pediatr. 1990;117(3):409–416. PMID: 2391596
  3. Bolton-Maggs PH, Stevens RF, Dodd NJ, et al. Guidelines for the diagnosis and management of hereditary spherocytosis — 2011 update. Br J Haematol. 2012;156(1):37–49. PMID: 22055020
  4. King MJ, Zanella A. Hereditary red cell membrane disorders and laboratory diagnostic testing. Int J Lab Hematol. 2013;35(3):237–243. PMID: 23448254
  5. Perrotta S, Gallagher PG, Mohandas N. Hereditary spherocytosis. Lancet. 2008;372(9647):1411–1426. PMID: 18940465
  6. Da Costa L, Galimand J, Fenneteau O, Mohandas N. Hereditary spherocytosis, elliptocytosis, and other red cell membrane disorders. Blood Rev. 2013;27(4):167–178. PMID: 23773192
  7. Delhommeau F, Cynober T, Schischmanoff PO, et al. Natural history of hereditary spherocytosis during the first year of life. Blood. 2000;95(2):393–397. PMID: 10627439
  8. Schilling RF. Risks and benefits of splenectomy versus no splenectomy for hereditary spherocytosis — a personal view. Br J Haematol. 2009;145(6):728–732. PMID: 19344414
  9. Rescorla FJ, Engum SA, West KW, et al. Laparoscopic splenectomy has become the gold standard in children. Am Surg. 2002;68(3):297–301. PMID: 11893027
  10. Casale M, Perrotta S. Splenectomy for hereditary spherocytosis: complete, partial or not at all? Expert Rev Hematol. 2011;4(6):627–635. PMID: 22077534
  11. Coombs AJ, Rogers AA, Reilly BK. Pediatric splenectomy: current trends in practice. J Pediatr Surg. 2009;44(12):2366–2371. PMID: 20006032
  12. Gallagher PG, Forget BG. Hematologically important mutations: spectrin and ankyrin variants in hereditary spherocytosis. Blood Cells Mol Dis. 1998;24(4):539–543. PMID: 9887281

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Connections

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