Anemia of chronic disease differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Omer Kamal, M.D.[2]

Overview

The most important differential is whether the patient has ACD alone or ACD with ongoing iron deficiency anemia (ACD/IDA). The following parameters will distinguish the two: Soluble transferrin receptor levels (sTfR) and/or the sTfR-ferritin index sTfR and the sTfR-ferritin index are normal in uncomplicated ACD, while both are elevated when IDA is also. Percentage of hypochromic red cells and reticulocyte hemoglobin may help.

Differential Diagnosis

Concomitant iron deficiency

The most important differential is whether the patient has ACD alone or ACD with ongoing iron deficiency anemia (ACD/IDA). The following parameters will distinguish the two:

●Soluble transferrin receptor levels (sTfR) and/or the sTfR-ferritin index sTfR and the sTfR-ferritin index are normal in uncomplicated ACD, while both are elevated when IDA is also present[1].

●Percentage of hypochromic red cells and reticulocyte hemoglobin may help[2][3].

Bone marrow examination in n difficult cases the diagnosis can often be established by bone marrow examination. Findings in the most common disorders include:

•ACD: Normal to increased iron in bone marrow macrophages while erythroid precursors may show decreased to absent iron

•Iron deficiency: No stainable iron in macrophages and erythroid precursors.

Myelodysplastic syndromes

Single or multi-lineage dysplastic changes with or without increased number of sideroblasts, including ring forms, are commonly seen in patients with myelodysplasia

Sideroblastic anemias

Presence of ring sideroblasts on bone marrow examination

●Serum erythropoietin (EPO) levels lower in ACD than in patients with IDA and comparable degrees of anemia[4].

●Oral iron supplementation for four to six weeks may help in the differentiation between ACD and ACD/IDA.

Chronic kidney disease (CKD)

Anemia in an older adult

Endocrine disorders

Hyperthyroidism, hypothyroidism, panhypopituitarism, and primary and secondary hyperparathyroidism may also present with a normocytic, normochromic hypoproliferative anemia.

Miscellaneous

IDA, thalassemia, sideroblastic anemias, and the sideroblastic variants of the myelodysplastic syndrome[5].

References

  1. Archer NM, Shmukler BE, Andolfo I, Vandorpe DH, Gnanasambandam R, Higgins JM, Rivera A, Fleming MD, Sachs F, Gottlieb PA, Iolascon A, Brugnara C, Alper SL, Nathan DG (December 2014). "Hereditary xerocytosis revisited". Am. J. Hematol. 89 (12): 1142–6. doi:10.1002/ajh.23799. PMC 4237618. PMID 25044010.
  2. Brugnara C (October 2003). "Iron deficiency and erythropoiesis: new diagnostic approaches". Clin. Chem. 49 (10): 1573–8. PMID 14500582.
  3. Thomas C, Thomas L (July 2002). "Biochemical markers and hematologic indices in the diagnosis of functional iron deficiency". Clin. Chem. 48 (7): 1066–76. PMID 12089176.
  4. Theurl I, Mattle V, Seifert M, Mariani M, Marth C, Weiss G (May 2006). "Dysregulated monocyte iron homeostasis and erythropoietin formation in patients with anemia of chronic disease". Blood. 107 (10): 4142–8. doi:10.1182/blood-2005-08-3364. PMID 16434484.
  5. DeLoughery TG (October 2014). "Microcytic anemia". N. Engl. J. Med. 371 (14): 1324–31. doi:10.1056/NEJMra1215361. PMID 25271605.


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