Hereditary Elliptocytosis Workup
- Author: Daniel J Kim, MD, MS; Chief Editor: Emmanuel C Besa, MD more...
Initial laboratory studies for the diagnosis of hereditary elliptocytosis (HE) include the following :
Complete blood cell count (CBC)
Peripheral blood smear
Direct antiglobulin test (Coombs test)
Reticulocyte count/immature reticulocyte fraction
Lactate dehydrogenase (LDH)
Microscopic examination of peripheral smears in patients with HE reveals that about 25% (sometimes nearly 100%) of cells are characteristically elliptical and often described as cigar-shaped. Some cases have fewer than 25% elliptocytes. Fragmented cells may also be seen.
Peripheral smear findings in subcategories of HE include the following:
Patients with hereditary pyropoikilocytosis (HPP) have an increased number of microspherocytes
Patients with stomatocytic elliptocytosis have distinctive, rounded elliptocytes bisected by a bar of hemoglobin, as described previously.
Elliptocytes can occur in many other conditions (eg, iron deficiency, leukemias, megaloblastic anemias, myeloproliferative diseases, myelodysplastic syndromes) but usually do not reach the proportions observed in patients with HE. Elliptocytes in patients with severe iron deficiency anemia are markedly hypochromic, a finding not associated with any of the HE disorders. Of most importance, patients with HE have a positive family history, whereas patients with other diseases associated with elliptocytes have underlying manifestations of their particular diseases.
Elliptocytosis must be differentiated from pseudoelliptocytosis, which is a common artifact of peripheral smear preparation. In pseudoelliptocytosis, the blood cells appear stretched and lined up in parallel, whereas in true elliptocytosis, the cells are oriented in different directions.
Results of osmotic fragility testing are within reference ranges in typical HE, but values are increased in spherocytic HE and HPP. When tested for thermal stability, normal RBCs can withstand temperatures up to 49°C, but RBCs associated with HPP denature at 45-46°C.
Laboratory studies may show evidence of hemolysis, such as low haptoglobin levels; a high reticulocyte count; and elevated concentrations of lactic dehydrogenase (LDH) and indirect bilirubin. It is important to emphasize that the percentage of elliptocytes observed does not correlate with the severity of hemolysis.
Although in most cases, the diagnosis of HE can be made without further studies, for further testing, International Council for Standardization in Haematology (ICSH) guidelines recommend SDS-polyacrylamide gel electrophoresis (SDS-PAGE) for quantitation of protein 4.1 and spectrin analysis (spectrin dimer content and spectrin variant), if those are available, or use of ektacytometry to obtain a deformability index (DI) proﬁle, which shows a characteristic trapezoidal shape in patients with HE.[5, 7]
Osmotic gradient ektacytometry has been the reference technique for diagnosis of RBC membrane disorders, but its limited availability has severely restricted its use. However, the recent introduction of a new generation of ektacytometers may allow wider application in clinical practice.
Imaging studies are not needed in the diagnosis of HE, but can reveal findings consistent with chronic hemolysis, such as splenomegaly and gallstones.
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