Iron deficiency anemia: Clinical sciences

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A 42-year-old woman presents for a follow-up of iron deficiency anemia secondary to menorrhagia. She has been taking oral iron supplementation (ferrous sulfate once daily) for 8 weeks. Her initial hemoglobin was 7.8 g/dL, serum iron was 28 μg/dL and ferritin was 8 ng/mL. She has been taking the medication as prescribed, on an empty stomach, and without food. She has been experiencing intermittent nausea, bloating, and constipation. Medical history is significant for uterine fibroids. Temperature is 36.8°C (98.2°F), pulse is 104/minute, respiratory rate is 16/minute, and blood pressure is 118/78 mmHg. Physical examination shows conjunctival pallor and pale nail beds. Cardiac examination shows tachycardia with regular rhythm. Lungs are clear to auscultation bilaterally. Laboratory results are shown below. Which of the following is the best next step in management?  
 
Laboratory value  Result
 Hemoglobin  8.0 g/dL 
 Hematocrit    38 % 
 MCV  76 fL  
 Iron  30 μg/dL 
 Ferritin  10 ng/mL 

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Iron deficiency anemia is a condition that occurs when the body lacks sufficient iron to produce enough healthy red blood cells.

Iron plays a vital role in the production of hemoglobin, which is the protein responsible for carrying oxygen in red blood cells. So, when iron levels are low, the body is unable to produce an adequate amount of hemoglobin, leading to a decrease in red blood cell production, and subsequent anemia. While history and physical examination findings can provide hints to iron deficiency anemia, confirming the diagnosis requires laboratory tests, primarily iron studies and a peripheral blood smear.

Now, if your patient presents with a chief concern suggestive of iron deficiency anemia, first, you should start with a focused history and physical examination.

History typically reveals vague symptoms like fatigue and dizziness, as well as palpitations and dyspnea on exertion, which manifest as compensatory responses to inadequate tissue oxygen supply.

Other symptoms may include pica, which is the compulsive consumption of non-nutritive substances like dirt or ice. Some patients may also develop Plummer-Vinson syndrome, which is characterized by the triad of iron deficiency anemia, esophageal webs, and dysphagia.

Additionally, some patients with iron deficiency may experience restless leg syndrome. Be sure to assess your patient’s nutritional history, since they might have a diet deficient in iron-rich foods. For example, the patient might report that they seldom eat red meat, leafy greens, and fortified grains, which are all rich in iron!

Next, your patient may have a history of gastrointestinal absorption problems that would prevent them from absorbing adequate dietary iron. These include inflammatory bowel disease, Helicobacter pylori infection, celiac disease, or a history of gastrointestinal surgery, such as bariatric surgery.

There may also be a history of chronic blood loss, which could be caused by gastrointestinal bleeding like in peptic ulcer disease or colon cancer, or by conditions like menorrhagia. Lastly, check if there are any increased iron requirements, which can be seen in conditions like pregnancy. Now, here’s a clinical pearl! Certain medications can potentially result in iron deficiency anemia such as nonsteroidal anti-inflammatory drugs or NSAIDs, which can increase the risk of peptic ulcers and subsequent bleeding; and proton pump inhibitors or PPIs, which can reduce absorption of iron. So, if you notice your patient has been using these medications, this should increase your suspicion of iron deficiency anemia.

Okay, now let’s move onto the physical exam, which typically reveals tachycardia and tachypnea, which are a compensatory response to reduced tissue oxygen delivery, as well as signs of pallor such as pale conjunctiva, lips, and nail beds. Other common findings include brittle nails and koilonychia, characterized by nails that are concave or spoon-shaped. Additionally, you might notice a smooth and glossy tongue, as well as cheilosis, which refers to inflammation and cracking at the corners of the mouth.

At this point, you should suspect iron deficiency anemia. Your next step is to order labs such as a CBC, reticulocyte count, serum iron, and serum ferritin as well as transferrin saturation or TSAT, total iron binding capacity or TIBC, and serum transferrin. Finally, don’t forget to request a blood smear.

Here’s a high yield fact to keep in mind! Hookworm infestations, such as Ancylostoma duodenale, can cause iron deficiency anemia. This occurs as hookworms cause damage to the gastrointestinal mucosa, leading to chronic gastrointestinal blood loss that overtime results in anemia. So, when you suspect a hookworm infestation, order a stool analysis to confirm.

Now, moving on to the lab results. The CBC typically reveals low red blood cell count with a low reticulocyte count; low mean corpuscular volume or MCV; decreased mean corpuscular hemoglobin concentration or MCH; increased red cell distribution width or RDW, as well as reduced hemoglobin and hematocrit.

Additionally, serum iron and ferritin levels are typically decreased, reflecting the reduced availability of iron in the blood. The TSAT, which is basically the percentage of occupied iron-binding sites on transferrin, is also reduced.

Sources

  1. "Clinical Practice Guidelines From the AABB" JAMA (2016)
  2. "Iron-Deficiency Anemia" New England Journal of Medicine (2015)
  3. "New insights into iron deficiency and iron deficiency anemia" Blood Reviews (2017)
  4. "Safety and efficacy of intravenous iron therapy in reducing requirement for allogeneic blood transfusion: systematic review and meta-analysis of randomised clinical trials" BMJ (2013)
  5. "Current Medical Diagnosis & Treatment. 62nd Edition" McGraw-Hill (2023)
  6. "Anaemia - Iron deficiency" National Institute for Health and Care Excellence (NICE) (2021)