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674 Part VI: The Erythrocyte Chapter 46: Erythrocyte Membrane Disorders 675

Typical Hereditary Spherocytosis Approximately 60 to 70 per- to detect carriers. In North America and parts of Europe, approximately
cent of HS patients have moderate disease, which typically presents in 1 percent of the population is estimated to be silent carriers. 63
infancy or childhood but may present at any age. In children, anemia is
the most frequent finding (50 percent of cases), followed by splenomeg- Pregnancy and Hereditary Spherocytosis
104
aly, jaundice, or a positive family history. 13,63 No comparable data exist Most patients do well during pregnancy although anemia may be
for adults. Hemolysis may be incompletely compensated with mild to exacerbated by plasma volume expansion and increased hemolysis. A
moderate anemia (see Table 46–3). The moderate anemia may often be few patients are symptomatic only during pregnancy. Transfusions are
asymptomatic; however, fatigue and mild pallor or both may be pres- rarely required.
ent. Jaundice may be intermittent and is seen in about half of patients,
usually in association with viral infections. When present, jaundice is Hereditary Spherocytosis in the Neonate
acholuric, characterized by unconjugated hyperbilirubinemia without Jaundice is the most common finding in neonates with HS, present in
detectable bilirubinuria. Palpable splenomegaly is evident in most (>75 approximately 90 percent of cases. It may be accentuated by coinher-
percent) older children and adults. Typically the spleen is modestly itance of Gilbert syndrome, caused by homozygosity for a polymor-
enlarged (2 to 6 cm below the costal margin), but it may be massive. phism in the promoter of the UGT1 gene (Chaps. 33 and 47). 63,97,98 Less
No proven correlation exists between the spleen size and the severity of than half of infants are anemic and severe anemia is rare. A few cases
HS. However, given the pathophysiology and response of the disease to of hydrops fetalis from homozygosity or compound heterozygosity for
splenectomy, such a correlation probably exists. band 3 or spectrin defects have been reported. 91,105,106
Mild Hereditary Spherocytosis Approximately 20 to 30 percent
of HS patients have mild disease with “compensated hemolysis,” that Complications
is, red blood cell production and destruction are balanced, and the Gallbladder Disease Chronic hemolysis leads to formation of biliru-
hemoglobin concentration of the blood is normal (see Table 46–3). 63,103 binate gallstones, the most frequently reported complication in up to half
The life span of spherocytes is decreased, but patients adequately com- of HS patients. Coinheritance of Gilbert syndrome markedly increases
pensate for hemolysis with increased marrow erythropoiesis. These the risk of gallstone formation. Although gallstones have been detected
patients are usually asymptomatic. Splenomegaly is mild, reticulocyte in children, they mainly occur in adolescents and young adults. 13,63
counts are generally less than 6 percent, and spherocytes on the blood Routine management should include interval ultrasonography to detect
film may be minimal, which complicates the diagnosis. Many of these gallstones because many patients with cholelithiasis and HS are asymp-
individuals escape detection until adulthood when they are being eval- tomatic. Interval ultrasonography allows prompt diagnosis and treat-
uated for unrelated disorders or when complications related to ane- ment and prevents complications of symptomatic biliary tract disease,
mia or chronic hemolysis occur. Hemolysis may become severe with including biliary obstruction, cholecystitis, and cholangitis.
illnesses that further increase splenomegaly, such as infectious mono- Hemolytic, Aplastic and Megaloblastic Crises Hemolytic crises
nucleosis, or may be exacerbated by other factors, such as pregnancy are the most common and are usually associated with viral illnesses and
or sustained, vigorous exercise. Because of the asymptomatic course typically occur in childhood. 13,63 They are generally mild and charac-
of HS in these patients, diagnosis of HS should be considered during terized by jaundice, splenomegaly, anemia and reticulocytosis. Medical
evaluation of incidentally noted splenomegaly, gallstones at a young intervention is seldom necessary. During rare severe hemolytic crises,
age, or anemia resulting from parvovirus B19 infection or other viral red cell transfusion may be required.
infections. Aplastic crises following virally induced marrow suppression are
Moderately Severe and Severe Hereditary Spherocytosis uncommon but may result in severe anemia requiring hospitalization
Approximately 5 to 10 percent of HS patients have moderately severe and transfusion with serious complications, including congestive heart
disease, as evidenced by indicators of anemia that are more pronounced failure or even death. 13,63 The most common etiologic agent in these
than in typical moderate HS, and an intermittent requirement for trans- cases is parvovirus B19 (Chap. 36). The virus selectively infects erythro-
fusions (see Table 46–3). This category includes patients with dominant poietic progenitor cells and inhibits their growth leading to the charac-
and recessive HS. A small number (<5 percent) of patients have severe teristic finding of a low number of reticulocytes despite severe anemia.
disease with life-threatening anemia and are transfusion-dependent. Aplastic crises usually last for 10 to 14 days and may bring asymptom-
They almost always have recessive HS. Most have severe spectrin defi- atic, undiagnosed HS patients with compensated hemolysis to medical
ciency, which is thought to result from a defect in α-spectrin, 78,79 but attention. 63
defects in ankyrin or band 3 have also been identified. 91,96 Patients with Megaloblastic crises may occur in HS patients with increased
severe HS often have irregularly contoured or budding spherocytes folate demands, such as pregnant patients, growing children, or patients
or bizarre poikilocytes in addition to typical spherocytes and micro- recovering from an aplastic crisis. This complication can be prevented
spherocytes on the blood film. Added to the risks of recurrent trans- with appropriate folate supplementation.
fusions, patients often suffer from hemolytic and aplastic crises and Other Complications Leg ulcers, chronic dermatitis on the legs
may develop complications of severe uncompensated anemia, including and gout are rare manifestations of HS, which usually heal rapidly after
growth retardation, delayed sexual maturation, and aspects of thalas- splenectomy. In severe cases, skeletal abnormalities resulting from
semic facies. expansion of the marrow can occur. Extramedullary hematopoiesis
Asymptomatic Carriers Parents of patients with recessive HS are can lead to tumors, particularly along the thoracic and lumbar spine
clinically asymptomatic and do not have anemia, splenomegaly, hyper- or in the kidney hila, in nonsplenectomized patients with mild to mod-
bilirubinemia, or spherocytosis on the blood films. However, most have erate HS. 13,63 Postsplenectomy, the masses involute and undergo fatty
subtle laboratory signs of HS (see Table 46–3), including slight reticulo- metamorphosis.
cytosis, diminished haptoglobin levels, and slightly elevated incubated HS has been suggested to predispose patients to hematologic
osmotic fragility, particularly the 100 percent red cell lysis point, which malignancies, including myeloproliferative disorders, particularly mye-
occurs at a higher sodium chloride concentration in carriers compared loma, but cause and effect have not been proven. Thrombosis has been
to normal subjects. The acidified glycerol lysis test may also be useful reported in several HS patients, usually postsplenectomy. Untreated HS
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