Hereditary Spherocytosis Workup

  • Author: Gus Gonzalez, MD; Chief Editor: Emmanuel C Besa, MD  more...
 
Updated: Oct 13, 2015
 

Approach Considerations

The principal laboratory studies used in the diagnosis of hereditary spherocytosis (HS) include the following:

  • Complete blood cell count
  • Reticulocyte count
  • Mean corpuscular hemoglobin concentration (MCHC)
  • Peripheral blood smear
  • Lactate dehydrogenase (LDH) level
  • Fractionated bilirubin
  • Osmotic fragility test

The classic laboratory features of hereditary spherocytosis (HS) include the following[1, 2] :

  • Mild to moderate anemia
  • Reticulocytosis
  • Increased MCHC
  • Spherocytes on the peripheral blood smear
  • Hyperbilirubinemia
  • Abnormal results on the osmotic fragility test

Red blood cell (RBC) morphology in HS is distinctive yet not diagnostic. Anisocytosis is prominent, and the smaller cells are spherocytes. Unlike the spherocytes associated with immune hemolytic disease and thermal injury, HS spherocytes are fairly uniform in size and density. Spherocytes are characterized by a lack of central pallor, decreased mean corpuscular diameter, and increased density.

Spherocytic RBCs are not specific to HS. Autoimmune hemolytic anemia also may produce spherocytosis, but this disorder usually can be excluded by negative findings on a direct antiglobulin test.

An increased MCHC is a characteristic feature of RBCs cells in HS. MCHC values greater than the upper limit of normal (35-36%) are common. This increased MCHC is a result of mild cellular dehydration. The mean cell volume (MCV) in patients with HS actually is low, presumably because of membrane loss and cell dehydration.

The most sensitive test for HS is the incubated osmotic fragility test, which is performed after incubating RBCs for 18-24 hours under sterile conditions at 37°C. Osmotic fragility testing with RBCs that have not been incubated may demonstrate hemolysis of HS cells in some patients but is not reliable. This is especially true of newborns, as fetal RBCs are generally more resistant to osmotic hemolysis. Incubated osmotic fragility test results usually are abnormal.

Other laboratory tests used to diagnose HS include the autohemolysis test and the glycerol lysis test. These rarely are used and offer no advantage over the osmotic fragility test.

Further characterization of the specific membrane lesion by looking for abnormalities in spectrin, ankyrin, pallidin, or band 3 is possible. However, these studies are not routinely performed and are available only in select research laboratories.

Other tests are indicated in patients who have experienced an aplastic crisis. Testing for herpes simplex virus, parvovirus B19, and infectious mononucleosis may help identify an infectious etiology for the aplastic crisis. Vitamin B-12 and folate levels should be measured to determine the nutritional stores during recovery from an aplastic crisis.

If the diagnosis is being made late in life, patients must have an evaluation of their iron status, especially if they have a history of frequent blood transfusions (eg, because of multiple hemolytic episodes or an inaccurate diagnosis) or if they have received prolonged oral iron supplementation for anemia. This evaluation includes measurement of iron stores and serum ferritin levels. Liver dysfunction or cardiac problems may be present in patients with severe iron overload.

Cholecystitis and cholelithiasis are common complications of HS. If the patient presents with signs and symptoms of hemolysis in addition to right upper abdominal quadrant pain, fever, and leukocytosis, an ultrasound of the biliary tree should be performed.

If an aplastic crisis is suggested, further evaluation of white blood cells and platelets should be pursued. This may require a bone marrow aspiration and biopsy to rule out aplasia or megaloblastosis. Obtaining bone marrow aspirate for testing rarely is necessary except in cases of aplastic or megaloblastic crisis. Test results help evaluate marrow function and the development of the lineage.

 
 
Contributor Information and Disclosures
Author

Gus Gonzalez, MD Medical Oncologist, The Center for Cancer and Blood Disorders

Gus Gonzalez, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine

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.

Ronald A Sacher, MB, BCh, FRCPC, DTM&H Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MB, BCh, FRCPC, DTM&H is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society on Thrombosis and Haemostasis, Royal College of Physicians and Surgeons of Canada, American Clinical and Climatological Association, International Society of Blood Transfusion

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: GSK Pharmaceuticals,Alexion,Johnson & Johnson Talecris,,Grifols<br/>Received honoraria from all the above companies for speaking and teaching.

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

Paul Schick, MD Emeritus Professor, Department of Internal Medicine, Jefferson Medical College of Thomas Jefferson University; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital

Paul Schick, MD is a member of the following medical societies: American College of Physicians, American Society of Hematology

Disclosure: Nothing to disclose.

Acknowledgements

E Randy Eichner, MD Professor, Department of Internal Medicine, University of Oklahoma Health Sciences Center

E Randy Eichner, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Sports Medicine, American Medical Society for Sports Medicine, and American Society of Hematology

Disclosure: Nothing to disclose.

References
  1. Bianchi P, Fermo E, Vercellati C, Marcello AP, Porretti L, Cortelezzi A, et al. Diagnostic power of laboratory tests for hereditary spherocytosis: a comparison study on 150 patients grouped according to the molecular and clinical characteristics. Haematologica. 2011 Nov 4. [Medline].

  2. [Guideline] Bolton-Maggs PH, Langer JC, Iolascon A, Tittensor P, King MJ. Guidelines for the diagnosis and management of hereditary spherocytosis - 2011 update. Br J Haematol. 2012 Jan. 156(1):37-49. [Medline].

  3. Abdullah F, Zhang Y, Camp M, Rossberg MI, Bathurst MA, Colombani PM, et al. Splenectomy in hereditary spherocytosis: Review of 1,657 patients and application of the pediatric quality indicators. Pediatr Blood Cancer. 2009 Jul. 52(7):834-7. [Medline].

  4. Perrotta S, Della Ragione F, Rossi F, et al. {beta}-spectrinBari: a truncated {beta}-chain responsible for dominant hereditary spherocytosis. Haematologica. 2009 Jul 16. epub ahead of print. [Medline]. [Full Text].

  5. Maciag M, Plochocka D, Adamowicz-Salach A, Burzynska B. Novel beta-spectrin mutations in hereditary spherocytosis associated with decreased levels of mRNA. Br J Haematol. 2009 Aug. 146(3):326-32. [Medline].

  6. Zaninoni A, Vercellati C, Imperiali FG, Marcello AP, Fattizzo B, Fermo E, et al. Detection of red blood cell antibodies in mitogen-stimulated cultures from patients with hereditary spherocytosis. Transfusion. 2015 Aug 10. [Medline].

  7. Perrotta S, Gallagher PG, Mohandas N. Hereditary spherocytosis. Lancet. 2008 Oct 18. 372(9647):1411-26. [Medline].

  8. Wang C, Cui Y, Li Y, Liu X, Han J. A systematic review of hereditary spherocytosis reported in Chinese biomedical journals from 1978 to 2013 and estimation of the prevalence of the disease using a disease model. Intractable Rare Dis Res. 2015 May. 4 (2):76-81. [Medline]. [Full Text].

  9. Teunissen M, Hijmans CT, Cnossen MH, Bronner MB, Grootenhuis MA, Peters M. Quality of life and behavioral functioning in Dutch pediatric patients with hereditary spherocytosis. Eur J Pediatr. 2014 Apr 16. [Medline].

  10. Christensen RD, Yaish HM, Gallagher PG. A pediatrician's practical guide to diagnosing and treating hereditary spherocytosis in neonates. Pediatrics. 2015 Jun. 135 (6):1107-14. [Medline].

  11. Casale M, Perrotta S. Splenectomy for hereditary spherocytosis: complete, partial or not at all?. Expert Rev Hematol. 2011 Dec. 4(6):627-35. [Medline].

  12. Morinis J, Dutta S, Blanchette V, Butchart S, Langer JC. Laparoscopic partial vs total splenectomy in children with hereditary spherocytosis. J Pediatr Surg. 2008 Sep. 43(9):1649-52. [Medline].

  13. Grace RF, Mednick RE, Neufeld EJ. Compliance with immunizations in splenectomized individuals with hereditary spherocytosis. Pediatr Blood Cancer. 2009 Jul. 52(7):865-7. [Medline].

  14. Rice HE, Englum BR, Rothman J, Leonard S, Reiter A, et al. Clinical outcomes of splenectomy in children: report of the splenectomy in congenital hemolytic anemia registry. Am J Hematol. 2015 Mar. 90 (3):187-92. [Medline].

  15. Agre P, Asimos A, Casella JF, McMillan C. Inheritance pattern and clinical response to splenectomy as a reflection of erythrocyte spectrin deficiency in hereditary spherocytosis. N Engl J Med. 1986 Dec 18. 315(25):1579-83. [Medline].

  16. Costa FF, Agre P, Watkins PC, et al. Linkage of dominant hereditary spherocytosis to the gene for the erythrocyte membrane-skeleton protein ankyrin. N Engl J Med. 1990 Oct 11. 323(15):1046-50. [Medline].

  17. Gallagher PG. Hematologically important mutations: ankyrin variants in hereditary spherocytosis. Blood Cells Mol Dis. 2005 Nov-Dec. 35(3):345-7.

  18. Glader BE, Naumovski L. Hereditary red blood cell disorders. In: Emery AE, Rimoin, DL, eds. Principles and Practice of Medical Genetics. New York, NY:. Churchill Livingstone. 1996.

  19. Hassoun H, Palek J. Hereditary spherocytosis: a review of the clinical and molecular aspects of the disease. Blood Rev. 1996 Sep. 10(3):129-47. [Medline].

  20. Hassoun H, Vassiliadis JN, Murray J, et al. Hereditary spherocytosis with spectrin deficiency due to an unstable truncated beta spectrin. Blood. 1996 Mar 15. 87(6):2538-45. [Medline].

  21. Korones D, Pearson HA. Normal erythrocyte osmotic fragility in hereditary spherocytosis. J Pediatr. 1989 Feb. 114(2):264-6. [Medline].

  22. Lee RD, Glader JN, Lukens JN. In: Lee GR, Foerster J, Lukens J, Paraskevas F, Greer JP, Rodgers GM, eds. Wintrobe's Clinical Hematology. 10th ed. Baltimore, Md: Lippincott Williams & Wilkins; 1999:. 1132-42.

  23. Nakashima K, Beutler E. Erythrocyte cellular and membrane deformability in hereditary spherocytosis. Blood. 1979 Mar. 53(3):481-5. [Medline].

  24. Peters LL, Lux SE. Ankyrins: structure and function in normal cells and hereditary spherocytes. Semin Hematol. 1993 Apr. 30(2):85-118. [Medline].

  25. Rice HE, Oldham KT, Hillery CA, et al. Clinical and hematologic benefits of partial splenectomy for congenital hemolytic anemias in children. Ann Surg. 2003 Feb. 237(2):281-8.

  26. Sackey K. Hemolytic anemia: Part 1. Pediatr Rev. 1999 May. 20(5):152-8; quiz 159. [Medline].

  27. Sackey K. Hemolytic anemia: Part 2. Pediatr Rev. 1999 Jun. 20(6):204-8. [Medline].

  28. Savvides P, Shalev O, John KM, Lux SE. Combined spectrin and ankyrin deficiency is common in autosomal dominant hereditary spherocytosis. Blood. 1993 Nov 15. 82(10):2953-60. [Medline].

  29. Stoehr GA, Stauffer UG, Eber SW. Near-total splenectomy: a new technique for the management of hereditary spherocytosis. Ann Surg. 2005 Jan. 241(1):40-7.

  30. Hsiao M, Sathya C, Nathens AB, de Mestral C, Hill AD, Langer JC. Is activity restriction appropriate for patients with hereditary spherocytosis? A population-based analysis. Ann Hematol. 2013 Apr. 92(4):523-5. [Medline].

 
Previous
Next
 
 
Medscape Consult
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.