OVERVIEW ― Iron deficiency is present if serum ferritin is < 12 ng/mL or < 30 ng/mL if also anemic. In adults, caused by bleeding unless proved otherwise. Causes include blood loss (gastrointestinal, menstrual, repeated blood donation), deficient diet or decreased absorption of iron and increased requirements (pregnancy, lactation). Women with heavy menstrual losses may require more iron than can reasonably be absorbed; thus, they often become iron deficient. Pregnancy and lactation also increase requirement for iron, necessitating medicinal iron supplementation. Long-term aspirin use may cause blood loss even without documented structural lesion. Search for a source of GI bleeding if other sites of blood loss (menorrhagia, other uterine bleeding, and repeated blood donations) are excluded
ASSESSMENT
SYMPTOMS AND SIGNS ― Easy fatigability, dyspnea, palpitations and tachypnea on exertion. In severe iron deficiency, skin and mucosal changes [e.g, smooth tongue, brittle nails, spooning of nails (koilonychia), and cheilosis] may develop. Dysphagia may occur. Pica (i.e, craving for specific foods [e.g, ice chips, lettuce] often not rich in iron) is common.
DIAGNOSIS
Diagnosis can be made by laboratory confirmation of an iron-deficient state and evaluation of response to a therapeutic trial of iron replacement.
LAB TESTS ― The reticulocyte count is low or inappropriately normal. Serum ferritin value < 12 mcg/L is a highly reliable indicator of reduced iron stores. However, because serum ferritin levels may rise in response to inflammation or other stimuli, a normal ferritin level does not exclude a diagnosis of iron deficiency. Ferritin level of < 30 ng/mL almost always indicates iron deficiency in anyone who is anemic.
Serum iron values decline to < 30 mcg/dL and transferrin levels rise to compensate iron deficiency, leading to transferrin saturations of < 15%. As deficiency progresses, anisocytosis (variation in red blood cell size) and poikilocytosis (variation in RBCs shape) develop. Abnormal peripheral blood smear: severely hypochromic RBCs, target cells, pencil-shaped or cigar-shaped cells in severe iron deficiency; platelet count is commonly increased, but it usually remains < 800,000/mcL. MCV falls, the blood smear shows hypochromic microcytic RBCs. Low hepcidin level is found in isolated iron deficiency anemia; however, this test is not yet clinically available
MANAGEMENT
ORAL IRON ― Ferrous sulfate, 325 mg orally once daily or every other day (Taken on an empty stomach is standard approach). Nausea and constipation limit patient compliance. Taking ferrous sulfate with food reduces side effects but also its absorption. Continue iron therapy for 3–6 months after restoration of normal hematologic values to replenish marrow iron stores. Ferric pyrophosphate citrate, additive to the dialysate designed to replace the 5 – 7 mg of iron that patients with chronic kidney disease tend to lose during each hemodialysis. Delivers sufficient iron to the marrow to maintain hemoglobin and not increase iron stores. May obviate the need for intravenous iron in hemodialysis patients.
Failure of response to iron therapy is usually due to noncompliance, occasional patients absorb iron poorly. Other reasons include incorrect diagnosis (anemia of chronic disease, thalassemia), celiac disease, and ongoing blood loss.
PARENTERAL IRON ― Indications for parenteral iron include intolerance of oral iron, refractoriness to oral iron, including hereditary iron-refractory iron deficiency anemia, GI disease (usually inflammatory bowel disease) precluding use of oral iron and continued blood loss that cannot be corrected. Parenteral iron preparations coat the iron in protective carbohydrate shells or contain low-molecular weight iron dextran, are safe, and can be administered over 15–60 minutes. The iron deficit is calculated by determining the decrement in RBC mass from normal recognizing there is 1 mg of iron in each milliliter of RBCs. Total body iron ranges between 2 g and 4 g: ~50 mg/kg in men and 35 mg/kg in women.
FOLLOW-UP ― Recheck CBC to observe for response to iron replacement by return of hematocrit to halfway toward normal within 3 weeks and fully to baseline after 2 months. Iron supplementation during pregnancy and lactation; iron is included in prenatal vitamins.
REFERENCES
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Auerbach M et al. Treatment of iron deficiency in the elderly: a new paradigm. Clin Geriatr Med. 2019 Aug;35(3):307–17. Available at: https://pubmed.ncbi.nlm.nih.gov/31230732
Powers JM et al. Disorders of iron metabolism: new diagnostic and treatment approaches to iron deficiency. Hematol Oncol Clin North Am. 2019 Jun;33(3):393–408. Available at: https://pubmed.ncbi.nlm.nih.gov/31030809
Camaschella C. Iron deficiency. Blood. 2019 Jan 3;133(1):30–9. Available at: https://pubmed.ncbi.nlm.nih.gov/30401704