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  • 2020–2021 BCSC Basic and Clinical Science Course™

    Go to Academy Store Learn more and Purchase.

    1 Update on General Medicine

    Chapter 8: Hematologic Disorders

    Anemia

    Anemia is the result of an insufficient quantity of erythrocytes to carry oxygen to the peripheral tissues. It can be classified according to 3 pathophysiologic states: (1) blood loss or nutritional deficiency, (2) underproduction of erythrocytes, and (3) premature destruction of erythrocytes (hemolysis). The normal hemoglobin level in men ranges from 14 to 17 g/dL, while the normal hemoglobin level in women is lower (12–16 g/dL). The higher level in men is due to the erythropoietic effects of androgens.

    In the evaluation of a patient with anemia, it is important for the clinician to classify the disorder by reviewing the RBC indexes, including complete blood count, hemoglobin concentration, and erythrocyte count, as well as indexes specifically indicative of RBC size: the mean corpuscular volume (MCV) of erythrocytes and their size distribution (red cell distribution width [RDW]). Reviewing these indexes and observing the morphology on a peripheral blood smear help the clinician determine whether the anemia is microcytic (MCV <80 femtoliter [fL]), normocytic (MCV 80–100 fL), or macrocytic (MCV >100 fL). In addition to the peripheral blood smear, the reticulocyte count gives an indication of erythrocyte production. Patients with normal bone marrow who have lost blood or undergone hemolysis have increased reticulocyte counts, whereas patients with underproduction anemia have low reticulocyte counts for their degree of anemia.

    Anemia Due to Blood Loss or Nutritional Deficiency

    Iron deficiency anemia

    By far, the most common type of anemia, affecting nearly 1 billion persons worldwide, is iron deficiency anemia. It is also the most common nutritional deficiency in the world. Iron deficiency anemia is diagnosed when the serum ferritin concentration is less than 15 μg/L or when transferrin saturation is less than 16%; the gold standard for diagnosis is the absence of stainable iron in the bone marrow.

    In developing countries, iron deficiency is typically caused by poor intake and/or parasitic infections, whereas in high-income countries, chronic blood loss, vegetarian or vegan diet, and poor absorption are the more common causes. Absorption can be affected by inflammatory bowel disease, celiac sprue, and Helicobacter pylori infection. Bariatric surgery is an increasingly common cause of iron deficiency.

    Iron deficiency anemia is also characterized by low hepcidin levels. Hepcidin, a peptide hormone produced by the liver, inhibits iron transport across the intestinal mucosa, thereby preventing excess iron absorption and maintaining normal iron levels within the body. Hepcidin also inhibits the transport of iron out of macrophages and enterocytes, that is, the site of iron storage and transport. Every adult with iron deficiency anemia should be suspected to be bleeding until proven otherwise. Menstrual blood loss in women plays a major role, as does gastrointestinal bleeding in both men and women. Aspirin can cause gastrointestinal bleeding.

    Patients with mild iron deficiency anemia may experience fatigue, malaise, irritability, decreased exercise tolerance, restless legs syndrome, and headaches before symptoms of overt anemia occur. Patients with iron deficiency anemia typically have normal findings on physical examination. However, in severe cases, abnormal findings such as facial pallor, glossitis, stomatitis, koilonychia (spoon nails), and conjunctival pallor may be present. Occasionally, patients with severe iron deficiency anemia exhibit pica, a tendency to eat ice, clay, starch, paper, or crunchy materials.

    Once the etiology of iron deficiency anemia has been identified, it may be treated with oral ferrous sulfate, which is the least expensive preparation for treating this disorder. It is typically administered at a dosage of 325 mg 3 times daily, although recent data suggest that an alternate-day dosing regimen may yield greater absorption of iron due to its favorable effect on hepcidin levels, with fewer gastrointestinal adverse effects. Parenteral iron preparations are indicated for patients who are unable to absorb oral iron, are intolerant of its adverse effects, are on dialysis, or have iron deficiency due to blood loss from inflammatory bowel disease.

    • Stoffel NU, Cercamondi CI, Brittenham G, et al. Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label randomised controlled trials. Lancet Haematol. 2017;4(11):e524–e533.

    Vitamin B12 deficiency

    Vitamin B12 comes from the diet and is available in all foods of animal origin. Absorption of vitamin B12 requires an intrinsic factor produced by the gastroparietal cells. This complex is absorbed in the terminal ileum and stored in the liver. It takes 3 years to deplete the reserves of vitamin B12 in the liver. Strict vegetarians (vegans), patients with a history of abdominal surgery or gastrectomy/bariatric surgery, and individuals with parasitic (tapeworm) or pancreatic disease are at increased risk for vitamin B12 deficiency. Pernicious anemia is an autoimmune disease in which atrophic gastritis and subsequent intrinsic factor deficiency lead to impaired vitamin B12 absorption. Megaloblastic anemia is a type of macrocytic anemia resulting from inhibition of DNA synthesis in RBC precursors in the marrow, leading to reduced cell division. When B12 levels are in the low normal range, the physician should examine levels of serum cobalamin B12, folate, homocysteine, and methyl-malonic acid (a more sensitive and specific test for diagnosing vitamin B12 deficiency). Often, leukopenia and thrombocytopenia accompany the anemia. Even in the absence of hematologic changes, vitamin B12 deficiency can cause a neurologic syndrome; peripheral nerves are affected first, while balance problems and alteration of cerebral function (eg, dementia, neuropsychiatric changes) occur in more severe cases. Parenteral B12 is used for treatment of pernicious anemia; otherwise, daily oral B12 is effective, less expensive, and less cumbersome than parenteral B12.

    Ophthalmic considerations Vitamin B12 deficiency may cause bilateral optic neuropathy presenting with central acuity loss and cecocentral scotomata on visual field testing.

    Folate deficiency

    Folate deficiency (also called folic acid deficiency) is another etiology of megaloblastic, or macrocytic, anemia. The most common etiology of the deficiency is inadequate dietary intake of folate due to generalized malnutrition or poor nutrition associated with alcohol dependence. Other causes of folate deficiency include

    • malabsorption (celiac disease or tropical sprue, zinc deficiency)

    • impaired metabolism (alcoholism, folate inhibitor drugs such as methotrexate and trimethoprim)

    • increased requirements (hemolytic anemia, pregnancy, lactation, infection, malignancy)

    • increased excretion (dialysis, subsequent to vitamin B12 deficiency)

    It is important to exclude vitamin B12 deficiency in patients with presumed folate deficiency; although treatment with folic acid can correct anemia in patients with vitamin B12 deficiency, it does not reverse the neuropsychiatric symptoms that can occur in severe B12 deficiency. Patients with folate deficiency may also develop neuropsychiatric symptoms that overlap with vitamin B12 deficiency. Once vitamin B12 deficiency is excluded, a therapeutic trial of folic acid in patients with presumed folate deficiency may be the most cost-effective way of establishing the diagnosis.

    Excerpted from BCSC 2020-2021 series: Section 1 - Update on General Medicine. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.

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    2022-2023 Basic and Clinical Science Course, Section 01: Update on General Medicine
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