Hereditary spherocytosis (HS) is the most common congenital hemolytic disorder among individuals of northern European descent. In most cases, it is an autosomal dominant disease that is caused by red blood cell (RBC) membrane protein defects, which render the RBCs more vulnerable to osmotic stress and hemolysis. Clinical presentation ranges from mild HS, which is generally asymptomatic, to severe HS, which can already present in utero with hydrops fetalis. Moderate HS, which is the most common form, usually presents in infancy or childhood with the classic triad of anemia, jaundice, and splenomegaly. Diagnosis is established based on family history, typical laboratory findings (e.g., elevated mean corpuscular hemoglobin concentration and RBC distribution width), and tests (e.g., eosin-5-maleimide binding test, osmotic fragility test). Treatment depends on the severity of the disease and involves acute measures (e.g., red blood cell transfusions, phototherapy), medication (e.g., folic acid supplementation), and splenectomy. HS patients are also at risk for complications such as hemolytic and aplastic crises, megaloblastic anemia, and gallstone formation.
- Incidence: 1/5000 in the US
- Most common inherited hemolytic disease among individuals of Northern European descent
Epidemiological data refers to the US, unless otherwise specified.
- Congenital RBC membrane protein defect
- Inheritance pattern
- Frequently affected proteins
Genetic mutation → defects in RBC membrane proteins (especially spectrin and/or ankyrin) responsible for tying the inner membrane skeleton with the outer lipid bilayer → continuous loss of lipid bilayer components → decreased surface area of RBCs in relation to volume → sphere-shaped RBCs with decreased membrane stability → inability to change form while going through narrowed vessels →
- Entrapment within splenic vasculature → splenomegaly
- Destruction via splenic macrophages → extravascular hemolysis
- Presentation is variable.
- Anemia and pallor
- Jaundice (due to ↑ unconjugated bilirubin)
- Splenomegaly with left upper quadrant pain
- Black pigment gallstones (made of calcium bilirubinate), may lead to cholecystitis
- Normocytic : mean cell volume (MCV) within normal range (80-100 fL) or slightly decreased
- Increased mean corpuscular hemoglobin concentration (MCHC)
- ↑ Red blood cell distribution width ; (↑ RDW)
- ↑ Reticulocytes (normal range: 0.5%–1.5% of total RBC count)
- Findings of
- Eosin-5-maleimide binding test (EMA)
- Other tests may be performed in addition to the EMA test.
- Negative : to exclude autoimmune hemolytic anemia (positive Coombs test), since spherocytosis is seen in both
Positive osmotic fragility test
- Measures the ability of RBCs to resist hemolysis when exposed to different degrees of salt dilution (e.g., RBCs swell and eventually lyse when incubated in hypotonic saline due to water influx)
- Whether or not RBCs lyse depends on their surface area to volume ratio. This ratio is decreased in patients with HS, so their RBCs are more fragile and more vulnerable to osmotic stress.
- Acidified glycerol lysis test
- Blood smear
- Ultrasound: to evaluate gallbladder complications (see , , and )
- Non-surgical treatments
- Hemolytic crisis: esp. as a result of viral infection
- Aplastic crisis: following infection with (erythema infectiosum); characterized by a low reticulocyte count (< 0.1% of total RBC count)
- Megaloblastic anemia: folate and vitamin B12 deficiency may develop due to chronic hemolysis and high RBC turnover
- Megaloblastic crisis: due to folate deficiency (although uncommon in developed countries, it might still be seen among pregnant women)
- Bilirubinate gallstone formation, possibly leading to cholecystitis, cholangitis, and pancreatitis
- Growth retardation and skeletal abnormalities due to bone marrow expansion
We list the most important complications. The selection is not exhaustive.