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A 15-year-old female presents to your office complaining of fatigue. She reports menarche at age 13 and complains of heavy menses. Her physical examination reveals a well-developed, well-nourished, pale female. You find no hepatosplenomegaly. Her laboratory results reveal a WBC 6,000/mm3, Hgb 8.9 g/dL, hematocrit 27%, platelet count 400,000/mm3, MCV 72 fL, red blood cell distribution width (RDW) 16. You order more laboratory tests.
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Question 6.11.1 What are the expected findings in this patient?
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A) Increased iron, decreased ferritin, increased total iron binding capacity.
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B) Decreased iron, decreased ferritin, decreased total iron binding capacity.
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C) Increased iron, increased ferritin, increased total iron binding capacity.
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D) Decreased iron, increased ferritin, decreased total iron binding capacity.
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E) Decreased iron, decreased ferritin, increased total iron binding capacity.
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Answer 6.11.1 The correct answer is "E." This patient likely has iron deficiency anemia related to her heavy menses. Iron deficiency anemia is characterized by anemia along with a decreased serum iron, decreased ferritin, increased total iron binding capacity (TIBC), and decreased transferrin saturation. The decrease in serum ferritin is proportional to the decrease in total body iron stores. Hypochromic microcytic RBCs are found on peripheral smear. See Table 6-3 for a general guide to the causes of anemia based on red cell indices.
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HELPFUL TIP:
The prevalence of VWD in women with menorrhagia ranges from 5% to 20%. Always make sure to take a good personal and family bleeding history.
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HELPFUL TIP:
Even if it looks like iron deficiency anemia, always consider other causes of anemia such as B12 deficiency, folate deficiency, and thalassemia. Often patients will have more than one cause for their anemia. Mixed vitamin B12 and iron deficiencies may present with normocytic anemia with an elevated RDW.
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You start iron supplementation therapy in this patient.
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Question 6.11.2 Which of the following tests will be the first to indicate that you have instituted appropriate therapy and that the patient is responding?
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A) Increase in hematocrit.
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B) Increase in reticulocyte count.
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C) Increase in serum-free Hgb.
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E) Decrease in transferrin saturation.
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Answer 6.11.2 The correct answer is "B." The patient's reticulocyte count will increase first—before the hematocrit ("A"). This should start soon after treatment and maximize at 7 to 10 days. Pica (if present) should also resolve fairly early. "C" is incorrect. Only in exceptional circumstances (intravascular hemolysis) will there be free hemoglobin in the blood. "D" is incorrect because the ferritin is low in iron deficiency anemia and should increase with therapy. Finally, transferrin saturation ("E") should increase in patients once you start to treat their anemia, but the reticulocyte count increases first.
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HELPFUL TIP:
Ferritin is not a useful test for iron deficiency in hospitalized patients or in those who are chronically ill. Ferritin is an acute-phase reactant and thus may be elevated in these patients even when the patient has iron deficiency anemia (where the ferritin should be low). However, you can check a soluble transferrin receptor. See below for more.
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HELPFUL TIP:
There may be no reticulocytosis with treatment of iron deficiency if the patient is simply iron deficient without anemia.
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Question 6.11.3 How long should you continue iron supplementation once the patient's labs have normalized?
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A) Stop immediately once anemia has resolved.
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B) Continue 3 to 6 months after the anemia has resolved.
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C) Continue for 1 year after the anemia has resolved.
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D) Indefinite iron supplementation is indicated.
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Answer 6.11.3 The correct answer is "B." Continue iron for 3 to 6 months once the anemia has resolved. Also address the underlying problem, in this patient her heavy periods, which may respond to hormonal contraception, tranexamic acid, etc.
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The patient returns in 2 months but her labs, if anything, are worse than at first presentation. The patient swears that she has been taking the iron faithfully.
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Question 6.11.4 Which of the following can lead to a failure of iron therapy for iron deficiency anemia?
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A) Proton pump inhibitors (PPIs).
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C) Oral antacids (e.g., calcium carbonate).
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D) Atrophic gastritis, celiac disease, or Helicobacter pylori infection.
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Answer 6.11.4 The correct answer is "E." Anything that neutralizes the stomach pH will interfere with absorption including PPIs, antacids, and loss of acid producing cells (e.g., pernicious anemia). Other GI diseases (celiac disease, H. pylori) can also interfere with iron absorption. Tea and some green leafy vegetables can also reduce iron absorption.
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HELPFUL TIP:
Vitamin C (supplements or orange juice) enhances iron absorption and should be considered if a patient is not responding to iron therapy. Meat can also increase iron absorption (which we hate to say because one of us is a vegetarian … however, the truth hurts).
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HELPFUL TIP:
A widened RDW and an elevated platelet count are typical of iron deficiency anemia. Conversely, the RDW will be normal in thalassemias.
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The patient returns to your office and finally admits she has not been able to take the iron because of side effects. Her hemoglobin is now down to 7.2 g/dL. She still feels fatigued. The patient will not agree to take any further iron orally. However, she is willing to consider other suggestions.
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Question 6.11.5 What is your next step?
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A) Encourage the patient to take the iron preparation along with calcium carbonate (Tums) to reduce the GI side effects.
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B) Continue her prenatal vitamin only and encourage her to eat more red meat.
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C) Give iron sucrose 200 mg IV weekly for 4 weeks.
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D) Transfuse 2 units of PRBCs immediately.
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Answer 6.11.5 The correct answer is "C." If oral iron preparations are not tolerated, IV iron preparations are available. Intramuscular preparations are best avoided due to pain at the injection site, skin discoloration, and risk for infection. The most commonly used options for IV replacement include iron dextran and iron sucrose. Iron dextran carries a risk of anaphylaxis in 0.6% to 2.3% of patients and other side effects in up to 25% of patients, including bronchospasm, flushing, headache, fever, urticaria, nausea, vomiting, hypotension, seizures, myalgias, arthralgias, and increased thromboembolic events. Iron sucrose has a lower incidence of side effects—typically nausea, constipation, diarrhea, or a transient minty taste—and may be given to patients who have had a previous reaction to iron dextran. "A" is incorrect because calcium will interfere with iron absorption. Not only that but also she has already said she would not take additional oral iron. "B" is incorrect because she needs more iron than can be provided through prenatal vitamins and her diet. Finally, "D" is incorrect as transfusion carries potential risks that could be avoided if she responds to IV iron replacement.
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HELPFUL TIP:
Any adult patient with microcytic anemia should be evaluated further to clarify the etiology. In adults, GI blood loss is a common cause of microcytic anemia. Colitis, malignancy, or malabsorption from inflammatory disease should be considered in the differential diagnosis. Tailor your work-up to the patient's symptoms. If he has symptoms referable to the upper GI tract (e.g., dyspepsia), consider an upper GI endoscopy in addition to colonoscopy.