Microcytic Anemia

Posted by • October 3rd, 2014

A new review discusses diagnosis and treatment of thalassemia, anemia of inflammation, and iron-deficiency anemia, highlighting recent findings.  The article includes an interactive graphic that shows various types of red cells that are observed in microcytic anemias and other conditions.

The microcytic anemias are those characterized by the production of red cells that are smaller than normal. The small size of these cells is due to decreased production of hemoglobin, the predominant constituent of red cells. The causes of microcytic anemia are a lack of globin product (thalassemia), restricted iron delivery to the heme group of hemoglobin (anemia of inflammation), a lack of iron delivery to the heme group (iron-deficiency anemia), and defects in the synthesis of the heme group (sideroblastic anemias).

Clinical Pearls

What is the mechanism of microcytosis in inflammatory states?

Inflammatory states are often accompanied by microcytic anemia. The cause of this anemia is twofold. First, renal production of erythropoietin is suppressed by inflammatory cytokines, resulting in decreased red-cell production. Second, lack of iron availability for developing red cells can lead to microcytosis. The lack of iron is largely due to the protein hepcidin, an acute-phase reactant that leads to both reduced iron absorption and reduced release of iron from body stores. The protein ferroportin mediates cellular efflux of iron. Hepcidin binds to and down-regulates ferroportin, thereby blocking iron absorbed by enterocytes from entering the circulation and also preventing the release of iron from its body stores to developing red cells.

Figure 2. Mechanism of Anemia of Inflammation.

Which persons are at greatest risk for iron deficiency anemia?

Owing to obligate iron loss through menses, women are at greater risk for iron deficiency than men. Iron loss in all women averages 1 to 3 mg per day, and dietary intake is often inadequate to maintain a positive iron balance. Pregnancy adds to demands for iron, with requirements increasing to 6 mg per day by the end of pregnancy. Athletes are another group at risk for iron deficiency. Gastrointestinal tract blood is the source of iron loss, and exercise-induced hemolysis leads to urinary iron losses. Decreased absorption of iron has also been implicated as a cause of iron deficiency, because levels of hepcidin are often elevated in athletes owing to training-induced inflammation. Obesity and its surgical treatment are also risk factors for iron deficiency. Obese patients are often iron-deficient, with increased hepcidin levels being implicated in decreased absorption. After bariatric surgery, the incidence of iron deficiency can be as high as 50%.

Morning Report Questions

Q: How is iron deficiency anemia diagnosed?

A: For the diagnosis of iron deficiency, many tests have been proposed over the years, but the serum ferritin assay is currently the most efficient and cost-effective test, given the shortcomings of other tests. The mean corpuscular volume is low with severe iron deficiency, but coexisting conditions such as liver disease may blunt the decrease in red-cell size. An increased total iron-binding capacity is specific for iron deficiency, but because total iron-binding capacity is lowered by inflammation, aging, and poor nutrition, its sensitivity is low. Iron saturation is low with both iron-deficiency anemia and anemia of inflammation. Serum levels of soluble transferrin receptor will be elevated in patients with iron deficiency, and this is not affected by inflammation. However, levels can be increased in patients with any condition associated with an increased red-cell mass, such as hemolytic anemias, and in patients with chronic lymphocytic leukemia. Bone marrow iron staining is the most accurate means of diagnosing iron-deficiency anemia, but this is an invasive and expensive procedure. Even in the setting of chronic inflammation, it is rare for a patient with iron deficiency to have a ferritin level of more than 100 ng per milliliter.

Q: What is the appropriate treatment for iron deficiency anemia?

A: Traditionally, ferrous sulfate (325 mg [65 mg of elemental iron] orally three times a day) has been prescribed for the treatment of iron deficiency. Several trials suggest that lower doses of iron, such as 15 to 20 mg of elemental iron daily, can be as effective as higher doses and have fewer side effects. The reason may be that enterocyte iron absorption appears to be saturable; one dose of iron can block absorption of further doses. Consuming the iron with meat protein can also increase iron absorption. Calcium and fiber can decrease iron absorption, but this can be overcome by taking vitamin C. A potent inhibitor of iron absorption is tea, which can reduce absorption by 90%. Coffee may also decrease iron absorption but not to the degree that tea does. With regard to dietary iron, the rate of absorption of iron from heme sources is 10 times as high as that of iron from nonheme sources. There are many oral iron preparations, but no one compound appears to be superior to another. A pragmatic approach to oral iron replacement is to start with a daily 325-mg pill of ferrous sulfate, taken with a meal that contains meat. Avoiding tea and coffee and taking vitamin C (500 units) with the iron pill once daily will also help absorption. If ferrous sulfate has unacceptable side effects, ferrous gluconate at a daily dose of 325 mg (35 mg of elemental iron) can be tried. The reticulocyte count should rise in 1 week, and the hemoglobin level starts rising by the second week of therapy. Iron therapy should be continued until iron stores are replete.

5 Responses to “Microcytic Anemia”

  1. dr s k gupta says:

    Great review. How about S Iron Levels for diagnosing iron def anemia

  2. dr suryakant dhoke says:

    Nice information on very common clinical problem.

  3. CJ Ewell says:

    Succinct and very helpful. Thank you.

  4. K Scheuermaier says:

    This reminds me of an interesting case I had ~10 years ago at our general hematology clinic. A young woman with chronic microcytic anemia who had received 3-4 courses of 4 months of ferrous sulfate although her ferritin levels were normal. I sent her for more thorough ultrasound testing just to exclude chronically bleeding fibromas. Incidentally, the radiologist examined the liver and found a large tumor which was excised and sent for pathology. It was a hepcidin secreting benign hepatoma. A rare but interesting diagnosis.

  5. Dr.M.Morsed Zaman Miah says:

    simple, easy, more informative.