Labs

The following is the complete blood count (CBC) the day you see the patient:

What’s what: WBC, white blood cell count; Hb, hemoglobin; MCV, mean cell volume; MCHC, mean cellular hemoglobin concentration; RDW-SD, red cell distribution width-standard deviation; platelets, PLT; Normal values: WBC 5-10 x 10⁹/L, RBC 4-6 x 10¹²/L, Hb 12-16 g/dL, Hct 35-47%, MCV 80-100 fL, MCHC 32-36 g/dL, RDW-SD < 45 fL, platelets (PLT) 150-450 x 10⁹/L

How would you describe the CBC?

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Normocytic, normochromic anemia with anisocytosis

The diagnostic algorithm for anemia begins with a mean cell volume and reticulocyte count:

The following was the patient’s reticulocyte count:

The absolute reticulocyte count, which is what we want to focus on is:

0.45 x 10¹²/L = 450 x 10⁹/L

Is the reticulocyte count appropriate for anemia?

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Yes! Any value > 0.2 x 10¹²/L or 120 x 10⁹/L is considered an appropriate response

Therefore, the patient has a hyperproliferative normocytic, normochromic anemia.

The patient was told she has thalassemia trait. However, her mean cell volume (MCV) is 86 fL. Does the normal MCV rule out thalassemia? If not, why?

We will take a look at the peripheral smear shortly. For now, consider the following questions:

What are the 2 major causes of anemia with elevated reticulocytes?

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1. Bleeding
2. Hemolysis

What other blood results would you like?

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Hemolysis markers!

If the patient has hemolytic anemia, what might you expect to find?

The following are the results of the hemolysis screen:

Are these data consistent with hemolysis?

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Yes. Not all markers have to be increased. In this particular condition, it is not uncommon to have an elevated indirect bilirubin but normal AST and LDH

Hemolytic anemia may be classified in several ways. One classification is intravascular vs. extravascular. The isolated elevation in indirect bilirubin without any increase in AST and LDH is most consistent with:

Now we can conclude that the patient has a hemolytic anemia, most likely congenital given her age and long history of anemia. What are possible causes of congenital hemolytic anemia?

The following table includes the more common causes of congenital hemolytic anemia. Fill in the peripheral smear findings (in addition to polychromatophilia from reticulocytosis) and relevant diagnostic tests.

The following table includes the more common causes of congenital hemolytic anemia. Fill in the peripheral smear findings (in addition to polychromatophilia from reticulocytosis) and relevant diagnostic tests.

The following is similar to the peripheral smear from the patient:

What is the next test you would like to perform?

Osmotic fragility test

Specimens for red cell osmotic fragility tests are anticoagulated with EDTA. Osmotic lysis is performed using sodium chloride (NaCl) solution, 0.50 g/dL. An incubated fragility test is performed following 24-hour incubation at 37 degrees C at the following NaCl concentrations: 0.60, 0.65, and 0.75 g/dL. Results are reported and interpreted.

Spherocytes are osmotically fragile cells that rupture more easily in a hypotonic solution than do normal RBCs. Because they have a low surface area: volume ratio, they lyse at a higher osmolarity than do normal red cells. Cells that have a larger surface area: volume ratio, such as target cells or hypochromic cells are more resistant to lysing. After incubation, an increase in hemolysis is seen in spherocytes. Hereditary spherocytosis typically has greater number of spherocytes than other causes of spherocytosis. Therefore, the degree of lysis is usually more pronounced, but this is not always the case. Some rare disorders can also cause marked fragility and hereditary spherocytosis cases can display moderate fragility.

Source.

These are the results of the patient’s osmotic fragility study:

How would you interpret these data?

The following is the interpretation of this patient’s osmotic fragility test:

Collectively, the data support a diagnosis of hereditary spherocytosis.

What do you expect the mean cell hemoglobin concentration to be in patients with hereditary spherocytosis?

The increased mean cell hemoglobin concentration is evident from the loss of central pallor in spherocytic cells. Consider the following schematic of red cells. Which of the following questions is/are correct?

A recent study examining red cell indices in patients with various hemoglobinopathies found that hereditary spherocytosis is indeed associated with an elevated mean corpuscular hemoglobin concentration (MCHC). It is interesting to note that the mean cell volume (MCV) is not decreased in patients with hereditary spherocytosis. One might expect that red cells that lose surface membrane would become smaller, and indeed they appear smaller on peripheral smears. It is possible that the normal MCV reflects a population of smaller than normal spherocytes and a population of larger reticulocytes.

Here again is the patient’s complete blood count.

What’s what: WBC, white blood cell count; Hb, hemoglobin; MCV, mean cell volume; MCHC, mean cellular hemoglobin concentration; RDW-SD, red cell distribution width-standard deviation; platelets, PLT; Normal values: WBC 5-10 x 10⁹/L, RBC 4-6 x 10¹²/L, Hb 12-16 g/dL, Hct 35-47%, MCV 80-100 fL, MCHC 32-36 g/dL, RDW-SD < 45 fL, platelets (PLT) 150-450 x 10⁹/L

Note that the mean corpuscular hemoglobin concentration (MCHC) is actually on the low side. As we saw from the last slide, this is not typical for hereditary spherocytosis.

As we will see in About the Condition, hereditary spherocytosis can be classified according to its clinical severity:

Let’s look at this patient’s parameters again:

How would you classify the patient?