Last updated: March 10, 2022

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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. 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; exact cutoffs vary from source to source.
  • WHO criteria for anemia [1]
    • Men: Hb < 13.5 g/dL
    • Women: Hb < 12 g/dL
    • Children
      • 6–59 months: < 11 g/dL
      • 5–11 years: < 11.5 g/dL
      • 12–14 years: < 12.0 g/dL
  • Revised WHO/National Cancer Institute [2]
    • Men: Hb < 14 g/dL
    • Women: Hb < 12 g/dL
  • American Society of Hematology [3]
    • Men: Hb < 13.5 g/dL
    • Women: Hb < 12 g/dL
  • US National Health and Nutrition Examination Survey: children aged 12–35 months: Hb < 11 g/dL

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

  • Morphology/size of RBCs (the classification most widely used) [4]
  • Time course: acute vs. chronic
  • Inheritance: inherited vs. acquired
  • Etiology: primary vs. secondary
  • RBC proliferation: hypoproliferative (decreased RBC production) vs. hyperproliferative (increased RBC destruction or blood loss)
Classification of anemia by morphology
Microcytic anemia Normocytic anemia Macrocytic anemia
MCV (fL)
  • < 80
  • 80–100
  • > 100
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.


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


  1. Check CBC to confirm anemia and assess severity.
  2. Based on MCV, classify into microcytic, macrocytic, and normocytic anemia.
  3. Order initial tests to evaluate the underlying cause of anemia.
  4. Consider advanced diagnostics such as hemoglobin electrophoresis and bone marrow aspirate and biopsy as needed and with the guidance of a hematologist.

Blood for further tests (e.g., iron studies, vitamin B12, folate levels) should be drawn before the patient receives a blood transfusion because blood products can alter the study findings.

CBC with differential

Initial test to confirm and classify anemia.

Microcytic anemia (MCV < 80 fL) [8][9]

Serum laboratory findings in microcytic anemia
Iron Ferritin Transferrin

Transferrin or TIBC Reticulocyte count

Red cell distribution width

Iron deficiency
Anemia of chronic disease Normal to ↓ Normal


Normal to ↑* Normal to ↑* Normal to ↑* Normal to ↓* Normal (occasionally ↑)
Sideroblastic anemia
Pregnancy or use of oral contraceptive pills Normal to ↓ Normal Normal Normal
* If there is iron overload (e.g., due to multiple transfusions, ineffective erythropoiesis, increased GI iron absorption)

Iron deficiency anemia and thalassemia trait are the most common causes of microcytic anemia. [9]

Basophilic stippling on peripheral blood smear suggests lead poisoning or sideroblastic anemia. Because ringed sideroblasts are not usually seen in lead poisoning, they can help to distinguish between this condition and sideroblastic anemia.

While decreased ferritin confirms the diagnosis of iron deficiency anemia, elevated serum ferritin does not rule it out.

Macrocytic anemia (MCV > 100 fL) [8][11][12][13]

Evaluation of megaloblastic macrocytic anemia

Serum methylmalonic acid levels are normal in folic acid deficiency and elevated in vitamin B12 deficiency. Serum homocysteine levels are elevated in both.

Evaluation of nonmegaloblastic macrocytic anemia [8][12]

The most common causes of macrocytosis are chronic alcohol consumption, vitamin B12 and/or folate deficiency, and certain medications. [12]

Normocytic anemia (MCV 80–100 fL) [8][11][13][16]

Additional diagnostics

Peripheral blood smear

Bone marrow biopsy


  • Imaging is not routinely indicated for the workup of anemia unless bleeding is suspected.
  • Consider endoscopy and/or colonoscopy in patients with anemia and positive FOBT.
  • Consider abdominal ultrasound to evaluate for hypersplenism, liver disease, or renal disease.
  • Consider CT and/or PET scan if malignancy is suspected.

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


References: [27]


Diamond-Blackfan anemia [29]

Hemoglobin and hematocrit levels can initially be normal in acute hemorrhage, even if there has already been significant blood loss. They will eventually decrease after plasma volume has been restored either spontaneously or via IV fluid resuscitation.

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