• Clinical science



Anemia is defined as a decrease in the number 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 either 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. Anemia is often an incidental finding made on CBC that requires further workup to determine the cause. The next best step is to obtain RBC indices, most importantly, the mean corpuscular volume (MCV), to distinguish between microcytic, normocytic, and macrocytic anemias based on the size of the RBCs. Size classification helps guide the next diagnostic step. A peripheral blood smear can serve to identify classic pathologic RBC forms. Reticulocyte count can serve to evaluate the bone marrow response. Since Hb levels initially remain normal in the setting of acute blood loss, it is important to monitor vital signs such as blood pressure and heart rate. Treatment depends on the form of anemia and may include supplementation (e.g., iron, vitamin B12, and folate), discontinuation of causative agents (e.g., in aplastic anemia), and stopping the source of bleeding or treating the underlying condition (e.g. in anemia of chronic disease). Acute and/or severe cases of anemia may require the transfusion of packed red blood cells.


  • Anemia is strictly defined as a decrease in absolute number of circulating RBCs, but more practically as a decrease in one of the RBC indices measured in the complete blood count(CBC): hemoglobin (Hb) concentration, RBC count, and hematocrit (Hct)
    • Rule of three; helps estimate the parameters: RBC multipled by 3 roughly estimates Hb, and Hb multiplied by 3 roughly estimates Hct (RBC x 3 = Hb, and Hb x 3 = Hct).
  • Criteria for anemia: Hb is the most commonly used criterion.
    • Men: Hb < 14 g/dl
    • Women: Hb < 12 g/dl
  • Reference values for adults
RBC (million/μl) 4.7–5.9 4.1–5.1
Hemoglobin (g/L) 14.0–17.4 12.3–15.3
Hematocrit (%) 42–50 36–44



Classification by cell size

There are many ways to classify anemias (e.g. cell size, mechanism, acute vs. chronic, inherited vs. acquired, primary vs. secondary). Classification by cell size is how hematologists begin their diagnostic work-up, and therefore has the most practical application.

Microcytic anemia (MCV < 80 fL)

Macrocytic anemia (MCV > 100 fL)

Normocytic anemia (MCV 80–100 fL)


Clinical features

  • 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
  • Features of extramedullary hematopoiesis in certain severe chronic anemias (e.g., thalassemia, myelofibrosis)
    • Hepatosplenomegaly
    • Paravertebral mass
    • Widening of diploic spaces of skull

Subtypes and variants

Aplastic anemia

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

Anemia of chronic disease

Pure red cell aplasia



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.


  • 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

Serum Iron Serum Ferritin % Iron saturation Transferrin/TIBC Reticulocyte count

Red cell distribution width (RDW)

Iron deficiency
Anemia of chronic disease 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)

MCV 80–100 fL = normocytic anemia

MCV > 100 fL = macrocytic anemia

Peripheral blood smear

  • May reveal classic pathologic RBC forms that can be used to identify certain types of anemia → see erythrocyte morphology

Bone marrow biopsy