What is the approach to diagnosing and managing anemia not caused by blood loss?

From the Guidelines

Diagnosing and managing non-hemorrhagic anemia requires a systematic approach beginning with a complete blood count and peripheral smear to characterize the anemia as microcytic, normocytic, or macrocytic, as recommended by the most recent guidelines 1. The initial step in evaluating anemia is to determine its cause, which can be achieved through a combination of morphologic and kinetic approaches. The morphologic approach involves characterizing the anemia based on the mean corpuscular volume (MCV), which can be microcytic, normocytic, or macrocytic 1.

• Microcytic anemia is often caused by iron deficiency, thalassemia, or anemia of chronic disease.
• Normocytic anemia may be caused by bone marrow failure, hemolysis, or renal insufficiency.
• Macrocytic anemia is typically megaloblastic, indicating vitamin B12 or folate deficiency.

The kinetic approach focuses on the underlying mechanism of anemia, distinguishing among the production, destruction, and loss of red blood cells (RBCs). The reticulocyte count corrected against the degree of anemia, or reticulocyte index (RI), is a useful measurement of RBC production capacity by the bone marrow 1.

• A low RI indicates decreased RBC production, suggesting iron deficiency, vitamin B12/folate deficiency, or bone marrow dysfunction.
• A high RI indicates normal or increased RBC production, suggesting hemolysis or blood loss.

Initial laboratory tests should include:

• Iron studies (serum iron, ferritin, total iron binding capacity) to diagnose iron deficiency anemia, with a ferritin level less than 30 ng/mL indicating absolute iron deficiency 1.
• Vitamin B12 and folate levels to diagnose deficiencies.
• Reticulocyte count to assess RBC production.
• Assessment of renal and liver function to identify potential underlying causes of anemia.

For iron deficiency anemia, oral ferrous sulfate 325mg daily or twice daily is recommended, taken on an empty stomach with vitamin C to enhance absorption, typically for 3-6 months to replenish iron stores, as supported by recent guidelines 1. Treatment of other causes of anemia includes:

• Vitamin B12 deficiency: intramuscular cyanocobalamin 1000mcg weekly for 4 weeks, then monthly, or oral supplementation at 1000-2000mcg daily.
• Folate deficiency: oral folic acid 1mg daily for 4 months.
• Anemia of chronic disease: treatment of the underlying condition.
• Erythropoiesis-stimulating agents like epoetin alfa may be considered for anemia related to chronic kidney disease, starting at 50-100 units/kg three times weekly, as discussed in recent guidelines 1. Follow-up monitoring should include repeat hemoglobin levels every 2-4 weeks initially to assess response to therapy, with the goal of identifying and addressing the specific cause rather than simply correcting the hemoglobin level.

From the FDA Drug Label

Evaluate iron status before and during treatment and maintain iron repletion. Correct or exclude other causes of anemia before initiating treatment ( 2.1).

The approach to diagnosing and managing anemia not caused by blood loss involves:

• Evaluating iron status before and during treatment
• Maintaining iron repletion
• Correcting or excluding other causes of anemia before initiating treatment It is essential to identify and address the underlying cause of anemia, and iron deficiency should be evaluated and managed accordingly 2.

From the Research

Approach to Diagnosing Anemia

• The initial evaluation of anemia consists of a thorough history and physical examination, and a complete blood cell count (CBC) 3.
• Careful examination of the CBC and the mean corpuscular volume provides important clues to the classification and cause of anemia 3.
• Supplemental tests may include a peripheral blood smear, reticulocyte count, iron panel, and levels of vitamin B12, folate, lactate dehydrogenase, haptoglobin, and bilirubin 3.

Laboratory Tests

• The first-line laboratory test for suspected anemia is the full blood count, which may suggest the anemia is caused by a nutritional deficiency of iron, vitamin B12, or folate 4.
• Laboratory measurement of the concentration in blood of iron, vitamin B12, and folate, along with several other tests, are useful in the differential diagnosis of anemic patients 4.
• A judicious workup of anemia includes evaluating the reticulocyte count and peripheral smear 5.

Evaluation of Iron Deficiency Anemia

• Iron deficiency anemia is a common cause of anemia, typically due to insufficient intake, poor absorption, or overt or occult blood loss 6.
• Distinguishing iron deficiency from other causes of anemia is integral to initiating the appropriate treatment 6.
• Identifying the underlying cause of iron deficiency is necessary to help guide management of these patients 6.

Diagnostic Tests

• The complete blood count with red cell indices offers clues to diagnosis, and many anemias have characteristic red cell morphology 7.
• The reticulocyte count serves as a useful screen for hemolysis or blood loss 7.
• Testing for specific causes of the anemia is performed, and occasionally, examination of the bone marrow is required for diagnosis 7.
• Molecular testing is increasingly being used to aid the diagnostic process 7.