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Mrs. A is a 48-year-old white woman who has had 2 months of fatigue due to anemia.

image What is the differential diagnosis of anemia? How would you frame the differential?


Anemia can occur in isolation, or as a consequence of a process causing pancytopenia, the reduction of all 3 cell lines (white blood cells [WBCs], platelets, and red blood cells [RBCs]). This chapter focuses on the approach to isolated anemia, although a brief list of causes of pancytopenia appears in Figure 6-1. The first step in determining the cause of anemia is to identify the general mechanism of the anemia and organize the mechanisms using a pathophysiologic framework:

Figure 6-1.
Diagnostic approach: anemia.

APLS, antiphospholipid syndrome; DIC, disseminated intravascular coagulation; ETOH, alcohol; G6PD, glucose-6-phosphate dehydrogenase; HELLP, hemolysis, elevated liver enzymes, and low platelet count; HUS, hemolytic uremic syndrome; MCV, mean corpuscular volume; SLE, systemic lupus erythematosus; TIBC, total iron-binding capacity; TTP, thrombotic thrombocytopenic purpura.

  1. Acute blood loss: this is generally clinically obvious.

  2. Underproduction of RBCs by the bone marrow; chronic blood loss is included in this category because it leads to iron deficiency, which ultimately results in underproduction.

  3. Increased destruction of RBCs, called hemolysis.

Patients should always be assessed for signs and symptoms of acute blood loss.

  1. Signs of acute blood loss

    1. Hypotension

    2. Tachycardia

    3. Large ecchymoses

  2. Symptoms of acute blood loss

    1. Hematemesis

    2. Melena

    3. Rectal bleeding

    4. Hematuria

    5. Vaginal bleeding

    6. Hemoptysis

After excluding acute blood loss, the next pivotal step is to distinguish underproduction from hemolysis by checking the reticulocyte count:

  1. Low or normal reticulocyte counts are seen in underproduction anemias.

  2. High reticulocyte counts occur when the bone marrow is responding normally to blood loss; hemolysis; or replacement of iron, vitamin B12, or folate.

  3. Reticulocyte measures include:

    1. The reticulocyte count: the percentage of circulating RBCs that are reticulocytes (normally 0.5–1.5%).

    2. The absolute reticulocyte count; the number of reticulocytes actually circulating, normally 25,000–75,000/mcL (multiply the percentage of reticulocytes by the total number of RBCs).

    3. The reticulocyte production index (RPI)

      1. Corrects the reticulocyte count for the degree of anemia and for the prolonged peripheral maturation of reticulocytes that occurs in anemia.

        • (1) Normally, the first 3–3.5 days of reticulocyte maturation occurs in the bone marrow and the last 24 hours in the peripheral blood.

        • (2) When the bone marrow is stimulated, reticulocytes are released prematurely, leading to longer maturation times in the periphery, and larger numbers of reticulocytes present at any given time.

        • (3) For a HCT of 25%, the peripheral blood maturation time is 2 days, and for a HCT of 15%, it is 2.5 days; the value of 2 is generally used in the RPI calculation.

      2. image

      3. The normal RPI is about 1.0. In the setting of anemia, ...

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