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Anemia Diagnostic Cascading Reflex

Test Code 37931

This test helps identify various anemias in both symptomatic and asymptomatic individuals. After the initial complete blood count (CBC), the reflex cascade is triggered only when results of certain red blood cell indices are out of range. The flow of testing is designed to minimize the time needed to identify the cause of anemia. The full algorithm is depicted in the Figure

Anemia of chronic disease is a normochromic, normocytic anemia caused by a diverse set of chronic diseases that include neoplastic, infectious, inflammatory, endocrine, metabolic, and end organ–related conditions, such as kidney failure. The most common causes are chronic infections, kidney disease, liver disease, autoimmune conditions, and malignancy.

Anemia of chronic disease is characterized by changes in iron metabolism, including decreased serum iron levels, decreased transferrin levels, decreased transferrin saturation, and normal to increased ferritin levels (reflex test in microcytic and normocytic anemia with abnormal CBC).1 Treatment of the underlying disease generally improves this type of anemia. Therefore, further evaluation should be focused on determining the identity of the underlying disease, if not already known. Often, history, physical, and laboratory results may suggest areas to investigate. For example, findings of normocytic anemia on a comprehensive metabolic panel may suggest liver disease, diabetes, or kidney disease. Review of the white blood cell count and differential may suggest an inflammatory condition or hematopoietic neoplasm.

For microcytic anemia, an unremarkable hemoglobinopathy evaluation combined with an in-range or low reticulocyte count suggests anemia of chronic disease (<25% of cases are microcytic).2 For macrocytic anemia with in-range or low reticulocyte count, high folate or B12 results reflex to liver function tests. Elevated liver enzyme levels distinguish chronic liver disease from hematologic diseases (eg, myelodysplasia).3,4

As part of the Anemia Diagnostic Cascading Reflex, sometimes a Hemoglobinopathy Evaluation (test code 35489) is performed. When no abnormal hemoglobin is identified, the MCV is decreased and the hemoglobin A2 is decreased, the differential diagnosis includes iron deficiency and alpha thalassemia. However, the Hemoglobinopathy Evaluation test does not assess for an alpha thalassemia mutation.

Quest Diagnostics has several tests available to help evaluate for alpha thalassemia, including the Alpha-Globin Common Mutation Analysis (test code 11175 [New York 11174]). Other tests include Alpha-Globin Gene Sequencing (test code 16116X [New York 16117X]) and the Alpha-Globin Gene Deletion or Duplication assay (test code 16124X [New York 16125X]).

Please call 1.866.436.3463 to discuss the case and additional testing options.


  1. Foucar K. Anemia of chronic disease and normochromic, normocytic non-hemolytic anemias. In: Kjeldsberg CR, Perkins SL, eds. Practical Diagnosis of Hematologic Disorders. ASCP Press; 2010.
  2. Gangat N, Wolanskyj AP. Anemia of chronic disease. Semin Hematol. 2013;50(3):232-238. doi:10.1053/j.seminhematol.2013.06.006
  3. Lanier JB, Park JJ, Callahan RC. Anemia in older adults. Am Fam Physician. 2018;98(7):437-442.
  4. Deligiannidis KE, Weissberger K. Anemia. 5MinuteConsult. Updated June, 2021. Accessed February 2, 2022.


This FAQ is provided for informational purposes only and is not intended as medical advice. Test selection and interpretation, diagnosis, and patient management decisions should be based on the clinician’s education, clinical expertise, and assessment of the patient.


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Version 0: Effective 07/25/2022 to present