History
The clinical presentation of hereditary elliptocytosis widely varies. Most patients are asymptomatic, and the diagnosis is usually made incidentally when a blood smear is examined. Asymptomatic patients are heterozygous for the condition and are classified as having mild or common hereditary elliptocytosis.
Approximately 10% of patients have moderate-to-severe anemia, with intermittent episodes of acute hemolysis with jaundice and splenomegaly. Patients with severe hereditary elliptocytosis or with hereditary pyropoikilocytosis are almost always homozygotes or compound heterozygotes. These patients are often transfusion dependent. Differences in clinical severity reflect manifestations of different mutations and are closely related to the extent of membrane surface area loss. [8]
All patients with conditions predisposing them hemolytic anemia are expected to be at risk of aplastic crisis during infection with parvovirus B-19.
Common or mild hereditary elliptocytosis
In neonates with common hereditary elliptocytosis, a precise diagnosis often cannot be established. The classic morphological findings may not be present.
Common hereditary elliptocytosis is rarely symptomatic in the neonatal period. Severe hemolytic anemia with poikilocytosis and jaundice may occasionally occur. Blood smear evaluation may reveal pyknocytes instead of elliptocytes. Pyknocytes are irregular, dense, distorted, spiculated RBCs similar to acanthocytes. Typically, elliptocytes do not appear in the blood until several months after birth.
Red blood cell survival is shorter than 120 days in neonates, particularly in premature neonates, so anemia may be severe. Anemia may be absent, however, if a persistent increase in reticulocyte production is able to compensate for hemolysis. [9]
Even when neonatal hemolysis is severe, this typically resolves by the time the patient is aged 12 months, and the anemia gradually improves.
Some neonates who present with moderate hemolysis and blood smear findings consistent with hereditary pyropoikilocytosis may have a course that gradually evolves into mild anemia with little or no hemolysis.
In children and adults, common hereditary elliptocytosis is usually asymptomatic or associated with mild sporadic hemolytic anemia.
The degree of hemolysis does not correlate with the percentage of elliptocytes seen in the blood.
The severity of hemolysis in common hereditary elliptocytosis varies not only among different kindreds but also within given families.
Spherocytic elliptocytosis
Spherocytic hereditary elliptocytosis is rare. The exact prevalence is unknown. Most patients have mild or moderate hemolysis. Blood smears show spherocytes, microspherocytes, and microelliptocytes. The elliptocyte percentage may be low.
Severe hereditary elliptocytosis and hereditary pyropoikilocytosis
Often, patients with homozygous hereditary elliptocytosis or hereditary pyropoikilocytosis have symptomatic hemolytic anemia that requires transfusion support and eventual splenectomy.
Many patients with hereditary pyropoikilocytosis present in the early newborn period with severe hemolytic anemia. Blood smears reveal RBC fragmentation, poikilocytosis, elliptocytosis, and microspherocytosis.
Neonatal hyperbilirubinemia and severe anemia in the first few months of life are typical.
Complications of severe anemia, including splenomegaly, growth retardation, frontal bossing, and early gallbladder disease, are common.
Southeast Asian ovalocytosis
Southeast Asian ovalocytosis is a mild form of elliptocytosis. Although this is a considered a benign disorder, neonates may experience hemolysis. The RBC membrane is rigid and hyperstable. Stomatocytes are RBCs with broad oval shapes and one or more stoma in a variety of orientations. [6] Hemolysis is minimal or absent outside of the newborn period.
Southeast Asian ovalocytosis confers some protection against Plasmodium falciparum and Plasmodium vivax infection. Individuals with Southeast Asian ovalocytosis have a significant reduction in the frequency and severity of cerebral malaria. [10]
Physical
Most patients have normal physical examination findings. Patients undergoing hemolysis may have signs of cardiovascular compromise, pallor, jaundice, and/or acute splenomegaly. Patients with severe forms may exhibit signs of chronic anemia, such as frontal bossing, failure to thrive, and chronic splenomegaly.
Adults may have skin ulcers. [11]
Causes
Hereditary elliptocytoses are inherited disorders. Some patients with bone marrow dysfunction have developed acquired hereditary elliptocytosis. [4]
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Cigar-shaped erythrocytes seen in hereditary elliptocytosis. Courtesy of Jean A. Shafer, BS, MA, Assistant Professor of Hematology and Pathology at the University of Rochester School of Medicine and Dentistry.
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Schematic diagram of the components of the RBC membrane. Hereditary elliptocytosis can result from defects of alpha or beta spectrin or from a defective spectrin-actin-protein 4.1R junctional complex.
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Bizarre RBC morphology seen in hereditary pyropoikilocytosis. Courtesy of Jean A. Shafer, BS, MA, Assistant Professor of Hematology and Pathology at the University of Rochester School of Medicine and Dentistry.
