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Hereditary Elliptocytosis Workup

  • Author: Daniel J Kim, MD, MS; Chief Editor: Emmanuel C Besa, MD  more...
 
Updated: Feb 09, 2016
 

Laboratory Studies

Initial laboratory studies for the diagnosis of hereditary elliptocytosis (HE) include the following[5] :

  • Complete blood cell count (CBC)
  • Peripheral blood smear
  • Direct antiglobulin test (Coombs test)
  • Bilirubin
  • Haptoglobin
  • Reticulocyte count/immature reticulocyte fraction
  • Potassium
  • 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.[6] 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.[8]

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Imaging Studies

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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Contributor Information and Disclosures
Author

Daniel J Kim, MD, MS Staff Physician, Department of Medicine, Olive View-UCLA Medical Center

Daniel J Kim, MD, MS is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Medical Association, American Society of Hematology, California Medical Association, Christian Medical and Dental Associations, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Marcel E Conrad, MD Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, SWOG

Disclosure: Partner received none from No financial interests for none.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Karen Seiter, MD Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College

Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology

Disclosure: Received honoraria from Novartis for speaking and teaching; Received consulting fee from Novartis for speaking and teaching; Received honoraria from Celgene for speaking and teaching.

Acknowledgements

Leland D Powell, MD, PhD Associate Clinical Professor of Medicine, David Geffen School of Medicine at UCLA; Consulting Staff, Department of Medicine, Olive View-UCLA Medical Center

Disclosure: Nothing to disclose.

References
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  2. Harper SL, Sriswasdi S, Tang HY, Gaetani M, Gallagher PG, Speicher DW. The common hereditary elliptocytosis-associated a-spectrin L260P mutation perturbs erythrocyte membranes by stabilizing spectrin in the closed dimer conformation. Blood. 2013 Aug 23. [Medline].

  3. Christensen RD, Nussenzveig RH, Reading NS, Agarwal AM, Prchal JT, Yaish HM. Variations in both α-spectrin (SPTA1) and β-spectrin ( SPTB ) in a neonate with prolonged jaundice in a family where nine individuals had hereditary elliptocytosis. Neonatology. 2014. 105 (1):1-4. [Medline].

  4. Keklik M, Unal A, Sivgin S, Kontas O, Eroglu E, Yilmaz S, et al. The coincidence of familial mediterranean Fever and hypereosinophilia in a patient with hereditary elliptocytosis. Indian J Hematol Blood Transfus. 2014 Sep. 30 (Suppl 1):138-41. [Medline].

  5. King MJ, Garçon L, Hoyer JD, Iolascon A, Picard V, Stewart G, et al. ICSH guidelines for the laboratory diagnosis of nonimmune hereditary red cell membrane disorders. Int J Lab Hematol. 2015 Jun. 37 (3):304-25. [Medline].

  6. King MJ, Zanella A. Hereditary red cell membrane disorders and laboratory diagnostic testing. Int J Lab Hematol. 2013 Jun. 35(3):237-43. [Medline].

  7. Silveira P, Cynober T, Dhermy D, et al. Red blood cell abnormalities in hereditary elliptocytosis and their relevance to variable clinical expression. Am J Clin Pathol. 1997 Oct. 108(4):391-9. [Medline].

  8. Da Costa L, Suner L, Galimand J, Bonnel A, Pascreau T, Couque N, et al. Diagnostic tool for red blood cell membrane disorders: Assessment of a new generation ektacytometer. Blood Cells Mol Dis. 2016 Jan. 56 (1):9-22. [Medline].

  9. Delaunay J. Genetic disorders of the red cell membrane. Crit Rev Oncol Hematol. 1995 Jun. 19(2):79-110. [Medline].

  10. Delaunay J. Molecular basis of red cell membrane disorders. Acta Haematol. 2002. 108(4):210-8. [Medline].

  11. Gallagher PG. Hereditary elliptocytosis: spectrin and protein 4.1R. Semin Hematol. 2004 Apr. 41(2):142-64.

  12. Gallagher PG, Romana M, Wong C, Forget BG. Genetic basis of the polymorphisms of the alphaI domain of spectrin. Am J Hematol. 1997 Oct. 56(2):107-11. [Medline].

  13. Nicolas G, Pedroni S, Fournier C, et al. Spectrin self-association site: characterization and study of beta- spectrin mutations associated with hereditary elliptocytosis. Biochem J. 1998 May 15. 332(pt 1):81-9. [Medline].

 
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