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Anemia is defined as a decrease in the quantity of circulating red blood cells (RBC), represented by a reduction in hemoglobin concentration (Hb), hematocrit (Hct), or RBC count. It is a common condition that can be caused by inadequate RBC production, excessive RBC destruction, or blood loss. The most common cause is iron deficiency. Clinical features, if present, are mostly nonspecific and may include fatigue, dyspnea, conjunctival pallor, and tachycardia. Once anemia has been established, the mean corpuscular volume (MCV) should be checked to distinguish between microcytic, normocytic, and macrocytic anemia and to determine the next diagnostic steps. A peripheral blood smear allows for the identification of pathologic RBC forms. Reticulocyte count can also be used to evaluate the bone marrow response. Treatment depends on the form of anemia and underlying condition. Acute and/or severe cases of anemia may require transfusion of packed red blood cells.

See basics of hematology, transfusion, and iron deficiency anemia for more information.


  • Definition: a decrease in the absolute number of circulating RBCs
  • WHO criteria for anemia [1]
    • Men: Hb < 13 g/dL
    • Women: Hb < 12 g/dL



Anemia may be classified into several subtypes based on the following methods:

  • Morphology/size of RBCs (the classification most widely used) [3]
  • Time course: acute vs. chronic
  • Inheritance: inherited vs. acquired
  • Etiology: primary vs. secondary
Classification of anemia by morphology
Microcytic anemia Normocytic anemia Macrocytic anemia
MCV (fL)
  • < 80
  • 80–100
  • > 100
  • Insufficient cell production and/or maturation
Differential diagnosis

Both iron deficiency anemia and anemia of chronic disease can manifest with normocytic anemia in the initial phase and microcytic anemia later on.

Bone marrow failure (e.g., due to myeloproliferative malignancy, myelodysplastic syndrome) can manifest with microcytic, normocytic, or macrocytic anemia.

The causes of microcytic anemia can be remembered with IRON LAST: IRON deficiency, Lead poisoning, Anemia of chronic disease, Sideroblastic anemia, Thalassemia.


Clinical features

Pulse acceleration is often the first sign of hemodynamically relevant blood loss.




Complete blood count (CBC) with RBC indices

  • MCV is the most important initial test in the diagnostic workup.
  • Based on RBC size, further testing should be performed to determine the underlying cause.

MCV < 80 fL = microcytic anemia [6]

Serum laboratory results in microcytic anemia
Iron Ferritin % Iron saturation Transferrin or TIBC Reticulocyte count

Red cell distribution width (RDW)

Iron deficiency
Anemia of chronic disease Normal to ↓ Normal


Normal to ↑* Normal to ↑* 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)

Basophilic stippling on peripheral blood smear suggests lead poisoning or sideroblastic anemia. Ringed sideroblasts are usually not seen in lead poisoning and can be used to distinguish between it and sideroblastic anemia.

MCV 80–100 fL = normocytic anemia

MCV > 100 fL = macrocytic anemia

Serum methylmalonic acid level can be used to distinguish between folic acid deficiency (normal) and vitamin B12 deficiency (high).

Peripheral blood smear

  • Manual examination of a peripheral blood sample under a microscope
  • May reveal classic pathologic RBC forms, which can be used to identify certain types of anemia that automated RBC indices cannot (e.g., schistocytes in hemolytic anemia)
  • See erythrocyte morphology.

Bone marrow biopsy



Acute management checklist

Aplastic anemia

Agents that can cause aplastic anemia: Can't Make New Blood Cells Properly = Carbamazepine, Methimazole, NSAIDs, Benzenes, Chloramphenicol, Propylthiouracil

References: [15][16][17][18][19]

Anemia of chronic disease


Sideroblastic anemia

References: [8]

Pure red cell aplasia