Update on Anemia

Educational Objectives

The goal of this program is to improve treatment of patients with anemia. After hearing and assimilating this program, the clinician will be better able to:

1. Select appropriate tests to evaluate patients with suspected iron deficiency.

2. Diagnose and treat patients with vitamin B12 deficiency.

Summary

Incidence of anemia: worldwide 25%; in US population 5%; in pregnant women 20%; in elderly people 11%; in individuals aged >85 yr ≈33%

Red blood cells (RBCs): circulate for 100 to 120 days; factors necessary for normal RBC count — stimulus (normal erythropoietin levels); normal precursor cells; essential nutrients; normal life span of RBCs

Complete blood count (CBC): laboratory tests measure hemoglobin directly; point-of-care tests measure hematocrit to calculate hemoglobin level; accuracy low when hematocrit <30%; red cell distribution width (RDW) — based on uniformity of RBCs; high in iron deficiency anemia (because of mix of small cells and slightly small cells); mean corpuscular volume (MCV) — ratio of hematocrit to RBC count; measure of size of RBCs; if RBCs large, consider vitamin B12 deficiency, folate deficiency, or alcoholic liver disease; if RBCs small, consider hereditary conditions or iron deficiency; mean corpuscular hemoglobin concentration (MCHC) — ratio of hemoglobin to hematocrit; mean concentration of hemoglobin in RBCs

Iron deficiency: cause of anemia with highest prevalence; 1% to 2% of US population affected (12% of women aged 20-45 yr); symptoms — fatigue; shortness of breath with exertion; dysphagia; pain with eating; esophageal issues; pallor; abnormalities of nails; stomatitis; angular cheilitis; glossitis; esophageal webs; headaches; ringing in ears; palpitations; disturbances in taste; pica; restless legs syndrome; hair loss; symptoms can be present without anemia

Metabolism of iron: human body contains 2 to 4 g iron (majority in hemoglobin); 1 mg/day iron required for men (1.4 mg/day for women); typical American diet provides ≈15 mg/day for men and 11 mg/day for women; ≤20% of iron absorbed from meat-containing diet; individuals consuming vegan diet at higher risk for iron deficiency; absorption of iron in proximal small intestine (highly regulated); gastric acid required for absorption of dietary iron; iron more easily absorbed when bound to heme

Hepcidin: hormone produced by liver; levels high in patients with poor absorption of iron; levels low in those with high iron absorption or hemochromatosis; causes of high hepcidin level — iron intake; inflammation; obesity; causes of low hepcidin level — iron deficiency; hypoxia; anemia of inflammation or chronic disease — iron bound to macrophages and not released; leads to poor absorption of iron

Causes of iron deficiency: loss of blood — menstruation; gastrointestinal (GI) blood loss; peptic ulcer disease; gastritis; parasites; vascular malformation; neoplasm (cause in ≈10% of older patients); Helicobacter pylori infection — promotes ulcers; can cause achlorhydria; obesity — rate of iron deficiency in adults with obesity ≈8%; ≤50% of patients become iron deficient after bariatric surgery; other causes — anemia in athletes due to high hepcidin levels or hemolysis; inflammatory bowel disease; celiac disease; aortic stenosis; daily use of nonsteroidal anti-inflammatory drugs (1 aspirin/day increases typical blood loss by 5 times); defects in metabolism and absorption of iron; congestive heart failure; medications (eg, antacids, proton pump inhibitors, H2 blockers)

Studies of iron: serum iron test; total iron binding capacity (TIBC) test; transferrin saturation test; ferritin test — most appropriate test for evaluating iron stores; 30 ng/mL normal in women (50 ng/mL in men); <15 ng/mL 99% specific for iron deficiency

Differential diagnosis for microcytic anemia: iron deficiency — serum iron level low; TIBC high; transferrin saturation low; ferritin level low; findings of hemoglobin electrophoresis normal; anemia of inflammation (anemia of chronic disease) — serum iron level low; TIBC low; transferrin saturation low normal; thalassemia trait — patient can present with mild microcytic anemia with normal findings of iron studies; other — sideroblastic anemia

Iron deficiency (continued): hypochromic microcytic anemia (presence of pale small RBCs); low MCV relatively late finding; patients with liver disease can be normocytic; elevated TIBC sensitive, but not specific; ferritin can be falsely elevated in inflammation (>100 ng/mL rare in iron deficiency); soluble transferrin receptor test distinguishes between anemia of inflammation and iron deficiency (findings elevated in iron deficiency and hemolysis; normal in anemia of inflammation)

Treatment of iron deficiency: oral iron — study found that starting with low dose of elemental iron (eg, 15 mg/day) as effective as 150 mg/day; taking iron with meat and vitamin C increases absorption; taking iron with tea or coffee inhibits absorption; foods that contain phytic acid inhibit iron absorption (eg, almonds); patients who take ferrous sulfate or ferrous gluconate (once daily or every other day) should respond within 2 wk; adverse effects include gastric erosions or gastritis; intravenous iron — appropriate in patients who cannot absorb oral iron; rate of mild reaction 1 in 200; rate of severe reaction 1 in 200,000; multiple infusions required for iron sucrose and ferrous gluconate; 1 or 2 infusions required for low-molecular-weight iron dextran (1000 mg)

Evaluation: perform upper and lower endoscopy; fecal occult blood test or fecal immunochemical test not sufficient to rule out malignancy

Thalassemia: causes abnormal ratios of α-globin to β-globin; hemoglobinopathy with highest prevalence; prevalent in Africa, India, and Middle East; prevalence of α-thalassemia high in China, Malaysia, Thailand, and Africa; 13% of people in Africa and 2% in United States heterozygous for β-thalassemia; consider thalassemia trait in patients with normal findings of hemoglobin electrophoresis (hemoglobin A2 level may be high), low MCV, and mild anemia

Vitamin B12 deficiency: cause of 1.5% of anemia in adults; Framingham study found rate of frank deficiency in advanced elderly 5%; of functional deficiency 6%; classic presentation — macrocytic anemia; abnormal white blood cells; yellow skin; impaired mentation; shuffling gait; causes — autoimmune disease (eg, pernicious anemia); gastrectomy; bariatric surgery; gastritis; small bowel disease; parasites; pancreatic insufficiency; vegan diet; medications (eg, metformin, proton pump inhibitors, H2 blockers); symptoms — symmetric paresthesias; abnormal gait; depression; irritability; cognitive dysfunction; dementia; psychosis; neurologic symptoms; GI symptoms; neurologic damage can occur without any abnormalities found on CBC; vitamin B12 level >300 pg/mL normal (200-300 pg/mL borderline; <200 pg/mL suggests deficiency); falsely low vitamin B12 levels can occur in pregnancy, with use of contraceptives or antiseizure drugs, in human immunodeficiency virus infection, or in multiple myeloma; levels may be falsely elevated because of malignancy, alcoholic liver disease, renal failure, and inborn errors of metabolism; confirmatory testing — elevated levels of methylmalonic acid and homocysteine indicate need for vitamin B12 supplementation; intrinsic factor antibody test confirms diagnosis of pernicious anemia; treatment — 1000 μg/day absorbed by majority of patients

Anemia of chronic disease: activation of immune system; can be caused by infection, cancer, autoimmune disease, or chronic kidney disease; hepcidin elevated (may slow growth of malignant cells); decreases iron absorption, impairs recycling of iron by macrophages, and decreases erythropoietin level; tests to distinguish iron deficiency anemia from anemia of chronic disease lacking; soluble transferrin receptor test may be most appropriate

Further workup: peripheral blood smear; hemolysis (especially in patients with elevated bilirubin levels); check reticulocyte count and lactate dehydrogenase levels; assess production and lysis of RBCs; if hemolytic process suspected, perform Coombs test; consider bone marrow biopsy

Readings

Arshad M et al: Effect of iron deficiency on the phenotype of β-thalassaemia trait. J Coll Physicians Surg Pak. 2016 Mar;26(3):230-1; Atanasiu V et al: Hepcidin — central regulator of iron metabolism. Eur J Haematol. 2007 Jan;78(1):1-10; Camaschella C: New insights into iron deficiency and iron deficiency anemia. Blood Rev. 2017 Jul;31(4):225-33; DeLoughery TG: Iron deficiency anemia. Med Clin North Am. 2017 Mar;101(2):319-32; Langan RC, Goodbred AJ: Vitamin B12 deficiency: recognition and management. Am Fam Physician. 2017 Sep 15;96(6):384-9; Low MS, Grigoriadis G: Iron deficiency and new insights into therapy. Med J Aust. 2017 Jul 17;207(2):81-7; Weiss G, Goodnough LT: Anemia of chronic disease. N Engl J Med. 2005 Mar 10;352(10):1011-23.

Disclosures

For this program, members of the faculty and planning committee reported nothing to disclose.

Acknowledgements

Dr. Adams spoke in Chattanooga, TN, at the 33rd Annual Family Medicine Update, presented June 13-16, 2018, by the University of Tennessee College of Medicine. Please visit uthsc.edu/continuing-medical-education for more information about upcoming events from this sponsor. The Audio Digest Foundation thanks the speakers and sponsors for their cooperation in the production of this program.

CME/CE INFO

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The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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Lecture ID:

FP671402

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.