Test Catalog

Interpretive Handbook

Test 84157 :
Hemolytic Anemia Evaluation

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Hemolytic anemia (HA) is characterized by increased red cell destruction and a decreased red cell life span. Patients usually have decreased hemoglobin concentration, hematocrit, and red blood cell count, but some can have compensated disorders, and symptoms such as reticulocytosis, pigmented gallstones, and decreased haptoglobin are factors that raise clinical suspicion. Blood smear abnormalities may include spherocytes, schistocytes, stomatocytes, polychromasia, basophilic stippling, and target cells. Osmotic fragility can be increased due to the presence of spherocytes. These are all nonspecific features that can be present in both hereditary and acquired hemolytic disorders. 


Inherited hemolytic disorders may include red cell membrane disorders, red cell enzyme defects, or abnormalities in the hemoglobin molecule in the red cell. This panel assesses for possible causes of congenital/hereditary causes of hemolytic anemia and does not evaluate for acquired causes. Therefore, the anemia should be lifelong or familial in nature. Examples of acquired HA (which should be excluded prior to ordering this panel) include: autoimmune HA, direct Coombs-positive HA, cold agglutinin disease, disseminated intravascular coagulation, and drug-induced HA.


This consultative evaluation looks for the cause of increased red cell destruction and includes testing for red cell membrane disorders, such as hereditary spherocytosis, hemoglobinopathies, and red cell enzyme abnormalities.


This panel is limited in use in patients with a history of recent transfusion and should be ordered as remote a date from transfusion as possible in those that are chronically transfused.

Useful For Suggests clinical disorders or settings where the test may be helpful

Evaluation of lifelong or inherited hemolytic anemias, including red cell membrane disorders, unstable or abnormal hemoglobin variants, and red cell enzyme disorders


Cold agglutinin disorders and autoimmune disorders should be excluded prior to testing. This evaluation is not suitable for acquired causes of hemolysis.

Interpretation Provides information to assist in interpretation of the test results

An interpretive report will be provided.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Preliminary screening tests, such as complete blood count with peripheral smear and direct Coombs test with a negative result, should be run before ordering this evaluation.


A normal shipping control for osmotic fragility (OF) is necessary to exclude false-positive results due to preanalytical artifact. OF and eosin-5-maleimide (EMA) binding testing will be canceled if no shipping control is received or if the shipping control is abnormal.


This panel is most effectively interpreted in the context of clinical information and the peripheral blood morphology. Please fill out the Hemolytic Anemia Patient Information sheet (T705) available in Special Instructions to maximize the interpretive capabilities of the panel.

This group of tests should not ordinarily be requested in patients who are likely to have immune hemolytic anemia (HA), such as that due to either warm or cold antibodies or to paroxysmal nocturnal hemoglobinurias. Coombs tests, tests for cold agglutinins, sucrose hemolysis, and Hams and Crosby tests are not part of the HA evaluation. In general, the foregoing tests should have been performed and found to be negative prior to requesting an HA evaluation. Since Wilson disease is another rare cause for acute intermittent hemolysis, testing for Wilson disease also may be appropriate prior to requesting an HA evaluation.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Definitive results and an interpretive report will be provided.

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Steiner LA, Gallagher PG. Erythrocyte disorders in the perinatal period. Semin Perinatol 2007 Aug;31(4):254-61. PMID: 17825683

2. Beutler E: Glucose-6-phosphate dehydrogenase deficiency and other enzyme abnormalities. In Hematology. Fifth edition. Edited by E Beutler, MA Lichtman, BS Coller, TJ Kipps. New York, McGraw-Hill Book Company, 1995, pp 564-581

3. Hoyer JD, Hoffman DR: The thalassemia and hemoglobinopathy syndromes. In Clinical Laboratory Medicine. Second edition. Edited by KD McMlatchey. Philadelphia, Lippincott, Williams and Wilkins, 2002, pp 866-895

4. King MJ, Garçon L, Hoyer JD, Iolascon A, et al: International Council for Standardization in Haematology. ICSH guidelines for the laboratory diagnosis of nonimmune hereditary red cell membrane disorders. Int J Lab Hematol 2015 Jun;37(3):304-25. PMID: 25790109

5. Lux SE, IV: Anatomy of the red cell membrane skeleton: unanswered questions. Blood 2016 Jan 14;127(2):187-99 DOI: 10.1182/blood-2014-12-512772. PMID: 26537302

6. Gallagher PG. Abnormalities of the erythrocyte membrane. Pediatr Clin North Am 2013 Dec;60(6):1349-62. PMID: 24237975

7. Bianchi P, Fermo E, Vercellati C, Marcello AP, et al: Diagnostic power of laboratory tests for hereditary spherocytosis: a comparison study in 150 patients grouped according to molecular and clinical characteristics. Haematologica 2012 Apr;97(4):516-23. PMID: 22058213

8. Cappellini MD, Fiorelli G. Glucose-6-phosphate dehydrogenase deficiency. Lancet 2008;371:64-74

9. Hereditary hemolytic anemias due to red blood cell enzyme disorders. Edited by B Glader. Philadelphia: Wolters Kluwer/Lippincott, Williams and Wilkins; 2014, pp 728

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