Table 1.

Practical exclusions to diagnose UAA

Potential cause of anemiaDefinition
Nutritional deficiencies Nutrient levels below reference range 
Iron deficiency  Ferritin <50 ng/mL 
B12 deficiency <200, <300 μmol/L with elevated MMA 
Folate deficiency < Lower limit of normal 
Blood loss Positive history of blood loss or positive fecal occult blood 
Anemia of inflammation Presence of known inflammatory condition that commonly causes anemia
Iron studies with low iron, elevated ferritin, low/normal TIBC 
Anemia of CKD  Estimated GFR <30 mL/min per 1.73 m2 
Thyroid disease TSH <0.1 or >10 ng/mL 
Medications Review medication list for medications that cause myelosuppression or drug-induced hemolysis 
Hemolytic disorders Review family history, hemolysis labs, and peripheral smear 
Warm or cold AIHA Positive direct antiglobulin test 
Hemoglobinopathies (eg, SCD or thalassemia) Sickled cells, target cells, and or hemoglobin C crystals on blood film, confirm diagnosis
Positive diagnosis by hemoglobin electrophoresis, HPLC, or genetic testing
MCV <80 fL, no iron deficiency is consistent with α- or β-thalassemia, confirm if possible 
Membranopathy (eg, hereditary spherocytosis) Abnormal red cell morphology on peripheral smear and inherited red cell membrane genetic defect 
Hematologic malignancy MDS is diagnosed if MDS diagnostic criteria are met
Diagnostic findings on BM or ancillary testing. Suspect if more severe anemia, other cytopenias, or macrocytosis 
Potential cause of anemiaDefinition
Nutritional deficiencies Nutrient levels below reference range 
Iron deficiency  Ferritin <50 ng/mL 
B12 deficiency <200, <300 μmol/L with elevated MMA 
Folate deficiency < Lower limit of normal 
Blood loss Positive history of blood loss or positive fecal occult blood 
Anemia of inflammation Presence of known inflammatory condition that commonly causes anemia
Iron studies with low iron, elevated ferritin, low/normal TIBC 
Anemia of CKD  Estimated GFR <30 mL/min per 1.73 m2 
Thyroid disease TSH <0.1 or >10 ng/mL 
Medications Review medication list for medications that cause myelosuppression or drug-induced hemolysis 
Hemolytic disorders Review family history, hemolysis labs, and peripheral smear 
Warm or cold AIHA Positive direct antiglobulin test 
Hemoglobinopathies (eg, SCD or thalassemia) Sickled cells, target cells, and or hemoglobin C crystals on blood film, confirm diagnosis
Positive diagnosis by hemoglobin electrophoresis, HPLC, or genetic testing
MCV <80 fL, no iron deficiency is consistent with α- or β-thalassemia, confirm if possible 
Membranopathy (eg, hereditary spherocytosis) Abnormal red cell morphology on peripheral smear and inherited red cell membrane genetic defect 
Hematologic malignancy MDS is diagnosed if MDS diagnostic criteria are met
Diagnostic findings on BM or ancillary testing. Suspect if more severe anemia, other cytopenias, or macrocytosis 

AIHA, autoimmune hemolytic anemia; GFR, glomerular filtration rate; HPLC, high-performance liquid chromatography; MMA, methylmalonic acid.

Ferritin levels in older adults and people with conditions such as chronic heart failure may experience absolute iron deficiency at ferritin levels up to 100 μg/L (or up to 300 μg/L if their TSAT is <20%).

CKD is more likely to be the cause of anemia when eGFR is <30 mL/min per 1.73m2; however, is still a possible diagnosis when the eGFR is <60 mL/min per 1.73m2. In older adults, the eGFR cutoff for excluding UAA is 30 mL/min per 1.73m2 if reversible causes are excluded.

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