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Microcytic Anemia for the Physician Assistant Exam

Microcytic anemias, characterized by a low MCV, usually < 79 fL, are covered on the Physician Assistant Exam (PANCE). The main microcytic anemias on the PANCE are iron-deficiency anemia, anemia of chronic disease, thalassemia, and lead poisoning. The key to answering these questions is to recognize the laboratory patterns.

Iron-deficiency anemia

Iron-deficiency anemia is the most common type of microcytic anemia. Here are the main causes of this kind of anemia:

  • Bleeding in the gastrointestinal (GI) tract, usually from the colon: This is the primary cause of iron-deficiency anemia. If a test question asks about new onset iron-deficiency anemia in an older adult, the test of choice is a colonoscopy to check for bleeding. You first need to rule out colon cancer. Besides a colonic malignancy, other causes of bleeding from the lower GI tract can include diverticulosis and angiodysplasia.

  • Malabsorption in the GI tract: Recall that iron is absorbed in the small intestine. If you see a test question in which a person has iron deficiency and no cause of bleeding can be identified, think malabsorption. The most common cause of malabsorption is celiac disease (sensitivity to gluten).

You need to order four labs to assess for iron deficiency: iron, transferrin, transferrin saturation, and ferritin. In iron-deficiency anemia, the ferritin level, which is a measure of storage iron, is low, and so is the TSAT. The transferrin level is high because the body wants to pick up as much iron from the circulation as possible.

Iron can be replaced two ways, either orally or intravenously. Ferrous sulfate is a commonly used oral iron replacement. Giving vitamin C at the same time as oral iron can increase the amount of iron absorbed in the intestine.

You started a patient on iron replacement for iron-deficiency anemia. Which of the following labs is initially used to monitor response to therapy?

(A) Ferritin level
(B) Repeat transferrin level
(C) Reticulocyte count
(D) Homocysteine level
(E) Haptoglobin level

The answer is Choice (C).

Which of the following is a cause of a microcytic anemia?

(A) Alcoholism
(B) Hypothyroidism
(C) Chronic liver disease
(D) Hemolysis
(E) Bleeding duodenal ulcer

The answer is Choice (E). The bleeding from a duodenal ulcer would cause an iron-deficiency anemia, which is a microcytic anemia.

Anemia of chronic disease

Anemia of chronic disease is also called anemia of inflammation. It’s a common cause of anemia, especially in older adults who have many complex medical conditions. You can see anemia with many inflammatory states, especially the connective tissue diseases, chronic infections and cancer.

Test questions about this kind of anemia usually include clues such as references to some long-standing disease, chronic infection, or inflammatory condition.

Ferritin is not only a measure of iron stores in the body but also a marker of inflammation, so it makes sense that a high ferritin level is a sign of anemia of chronic disease. Ferritin can be elevated in inflammatory states or connective tissue disease. In medical conditions like Still’s disease, it can even be > 3,000 ng/mL.

Thalassemia

Thalassemia is a type of microcytic anemia that’s important to recognize because the test always includes a question or two about it. Thalassemia is very common in people of African or Mediterranean descent.

You may recall that hemoglobin is made of two different types of protein: beta globin and alpha globin. Thalassemia is a hereditary condition concerning a problem in the gene that makes one of these two proteins, leading to anemia. If a gene that makes beta globin is affected, then you have beta thalassemia. If a gene that makes alpha globin is affected, then you can have alpha thalassemia.

Both beta globin and alpha globin can have their own major and minor problems. Therefore, you can see a beta thalassemia major and minor and an alpha thalassemia major and minor.

If someone has thalassemia major, he or she inherited the problem gene from both parents. If someone has thalassemia minor, the problem gene came from only one parent. Two types of beta thalassemia and four types of alpha thalassemia exist because two genes code for beta globin, and four genes code for alpha globin.

Here are a couple of key points concerning the thalassemias:

  • Beta thalassemia minor (beta thalassemia trait): The affected person can have a microcytosis but with a very mild anemia. You’ll see target cells on a peripheral smear.

  • Beta thalassemia major: The person can be severely affected as a child. He or she can develop a hemolytic anemia, problems with growth, and congestive heart failure because the anemia causes a high output state. Patients can also develop a very large liver and spleen, which for many can be fatal at a young age. Those who survive are often transfusion dependent and can develop problems with iron overload.

There are four basic alpha thalassemias. They can range in severity from being asymptomaticto being fatal in utero. Alpha thalassemia minor is a lot like beta thalassemia minor in its presentation: mild microcytosis.

You can confirm the diagnosis of thalassemia with a hemoglobin electrophoresis.

Lead poisoning

Lead poisoning is a condition you commonly see in young children exposed to lead. This exposure occurs especially in people who live in older homes that contain lead paint. Lead gets into the body when people eat it or inhale small particles into the lungs. It causes anemia, primarily by inhibiting the synthesis of heme.

Here are two key points concerning lead poisoning and anemia:

  • On a peripheral smear, you can see basophilic stippling.

  • Ferritin and iron levels can be normal.

The treatment for lead poisoning is chelation, depending on the presenting symptoms and the lead level.

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