CLINICAL PICTURE

• Exertional dyspnea and fatigue

• Pallor (most evident on mucous membranes, in particular, the conjunctiva)
• Muscle cramps
• Possibly tachycardia
• Bounding pulses, palpitations, pulsatile sound in the ear
• Worsening of angina pectoris

DIAGNOSIS
The diagnosis of anemia is made based on hemoglobin, hematocrit, or RBC count. After determining that anemia is present,
workup for the cause of anemia is required.
History
• Bleeding (history of recent trauma or surgery, menorrhagia, melena, hematemesis)
• Hemolysis (jaundice, gallstones)
• Chronic diseases
• Medications
• Family history (e.g., inherited anemias and hemophilia)
• Social history (alcohol)
Complete blood count (CBC) with the RBC indices
MCV is the most important test in the diagnostic workup. Based on RBC size, further tests should be ordered to determine the
diagnosis.

MCV < 80 fL = microcytic anemia

• Iron studies: serum iron, ferritin , transferrin/total iron binding capacity (TIBC), % iron saturation
• Reticulocyte count
• If iron studies are normal: workup for hemolytic anemia
• If iron deficiency is suspected: further workup for causes of bleeding
• If thalassemia is suspected: hemoglobin electrophoresis
• If sideroblastic anemia is suspected: cell staining with Prussian blue reveals ringed sideroblasts (for more information on
staining, see Prussian blue reaction)
Serum Serum % Iron Reticulocyte Red cell distribution
Transferrin/TIBC
Iron Ferritin saturation count width (RDW)
Iron deficiency ↓ ↓ ↓ ↑ ↓ ↑
Anemia of chronic
↓ ↑ ↓ ↓ ↓ Normal
disease
Normal to Normal to
Thalassemia Normal to ↑* Normal to ↓* Normal or ↑ Normal (occasionally ↑)
↑* ↑*
Sideroblastic
↑ ↑ ↑ ↓ ↓ ↑
anemia
* If iron overload is present (e.g., due to multiple transfusions, ineffective erythropoiesis, ↑ GI iron absorption)

MCV 80–100 fL = normocytic anemia

• Reticulocyte count: evaluate bone marrow response
o Low reticulocyte count: ineffective or decreased RBC production, e.g., chronic renal failure, aplastic anemia (look for possible
causative agents; see “Subtypes and variants” above), ACD, and cancer/dysplasia (e.g., acute leukemia)
o High reticulocyte count: increased RBC destruction (hemolysis) or blood loss
o Normal or elevated reticulocyte count: acute blood loss and hemolysis
MCV > 100 fL = macrocytic anemia
• Folate and/or vitamin B12 levels: decreased levels may cause megaloblastic anemia:
o Appearance of hypersegmented neutrophils (megaloblastic) on peripheral blood smear
o ↓ Reticulocytes, ↑ iron
o Bone marrow (not required): erythroid hyperplasia
o In vitamin B12 deficiency: workup for causes such as type A gastritis and ileal disease (e.g., Crohn's disease)
• Evaluate for myelodysplastic syndromes
• Evaluate other cell lines (may also be affected)

Peripheral blood smear

• May reveal classic pathologic RBC forms, can be used to identify certain types of anemia → see erythrocyte morphology
Bone marrow biopsy
• Invasive procedure that is rarely used in the workup of anemia
• Indications include pancytopenia and the finding of abnormal cells on the complete blood count or the peripheral blood
smear such as blasts.
• Anemia accompanied by one of those findings may be caused by aplastic anemia, myelodysplastic syndromes,
myeloproliferative neoplasm, or malignancy replacing the bone marrow.