eMedicine Specialties > Hematology > Red Blood Cells and Disorders

Spherocytosis, Hereditary: Differential Diagnoses & Workup

Author: Gus Gonzalez, MD, Medical Oncologist, The Center for Cancer and Blood Disorders
Coauthor(s): E Randy Eichner, MD, Professor, Department of Internal Medicine, University of Oklahoma Health Sciences Center
Contributor Information and Disclosures

Updated: Aug 27, 2009

Differential Diagnoses

Anemia
Cholelithiasis
Biliary Colic
Hemolytic Anemia
Biliary Disease
Hyperbilirubinemia, Conjugated
Biliary Obstruction
Hyperbilirubinemia, Unconjugated
Cholecystitis

Workup

Laboratory Studies

  • The classic laboratory features of HS include minimal or no anemia, reticulocytosis, an increased mean corpuscular hemoglobin concentration (MCHC), spherocytes on the peripheral blood smear, hyperbilirubinemia, and abnormal results on the osmotic fragility test.
    • RBC morphology 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.
    • Other biochemical changes of hemolysis also are present, including increased lactate dehydrogenase (LDH), increased unconjugated bilirubin, and decreased serum haptoglobin. RBC indices demonstrate an increase in MCHC.
  • An increased MCHC obtained from an electronic cell counter is a characteristic feature of red 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. This relatively low MCV may reflect membrane loss and cell dehydration.
  • The most sensitive test to help detect HS is the incubated osmotic fragility test performed after incubating RBCs for 18-24 hours under sterile conditions at 37°C.
    • Hemolysis of HS cells may be complete at a solute concentration that causes little or no lysis of normal cells.
    • Not uncommonly, some individuals with HS have a normal fresh osmotic fragility test result.
    • Osmotic fragility after prolonged incubation at 37°C usually is 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 characterizing the specific membrane lesion by looking for abnormalities in spectrin, ankyrin, pallidin, or band 3 is possible. However, these studies are not routine and are available only in select research laboratories.
  • The initial workup if hemolysis is suggested should include the following:
    • Reticulocyte count
    • Lactate dehydrogenase
    • Fractionated bilirubin
    • Haptoglobin
    • Peripheral smear: Howell-Jolly bodies may be present, indicating remnant splenic tissue if the patient has had their spleen removed. Findings also may include megalocytosis.
    • Vitamin B-12 and folate: This should be measured to determine the nutritional stores during recovery from an aplastic crisis.
    • Herpes simplex virus, HPV type 19, and infectious mononucleosis: Testing for these may help identify an infectious etiology for the aplastic crisis.
  • If the diagnosis is being made late in life, patients must have an evaluation of their total iron body stores, especially if the patient has a history of frequent blood transfusions. Liver dysfunction or cardiac problems may be present in patients with severe iron overload. This evaluation includes tests for iron stores and serum ferritin levels.

Imaging Studies

  • 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 to help exclude cholecystitis or cholelithiasis.

Procedures

  • If an aplastic crisis is suggested, further evaluation of WBCs and platelets should be pursued. This may require a bone marrow biopsy and aspirate 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.

Histologic Findings

Anemia, reticulocytosis, and spherocytosis on peripheral blood smear examination provide strong hints to suggest the diagnosis of HS. Spherocytic RBCs are not specific to HS. Autoimmune hemolytic anemia also may produce spherocytosis, which usually can be excluded by negative findings on a direct antiglobulin test.

More on Spherocytosis, Hereditary

Overview: Spherocytosis, Hereditary
Differential Diagnoses & Workup: Spherocytosis, Hereditary
Treatment & Medication: Spherocytosis, Hereditary
Follow-up: Spherocytosis, Hereditary
References
Further Reading
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References

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

  2. 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. Aug 2009;146(3):326-32. [Medline].

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

  4. 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. Jul 2009;52(7):834-7. [Medline].

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

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

  7. 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. Dec 18 1986;315(25):1579-83. [Medline].

  8. 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. Oct 11 1990;323(15):1046-50. [Medline].

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

  10. 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.

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

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

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

  14. 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.

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

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

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

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

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

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

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

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Further Reading

Related eMedicine Topics

Clinical Trials

National Guideline Clearinghouse

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Keywords

hereditary spherocytosis, HS, congenital spherocytosis, familial hemolytic disorder, hemolytic anemia, anemia, blood disorder, hereditary hemolytic anemia, aplastic crisis, megaloblastic crisis, hemolytic crisis, cholecystitis, cholelithiasis, neonatal hemolysis, splenomegaly

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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.

Coauthor(s)

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.

Medical Editor

Paul Schick, MD, Emeritus Professor, Department of Internal Medicine, Thomas Jefferson University Medical College; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital, Wynnewood, PA
Paul Schick, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Hematology, International Society on Thrombosis and Haemostasis, and New York Academy of Sciences
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Ronald A Sacher, MB, BCh, MD, FRCPC, Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center
Ronald A Sacher, MB, BCh, MD, FRCPC is a member of the following medical societies: American Society of Hematology
Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; Talecris Honoraria Board membership

CME Editor

Rajalaxmi McKenna, MD, FACP, Consulting Staff, Department of Medicine, Southwest Medical Consultants, SC, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

 
 
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