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iron-deficiency anemia

Microcytic hypochromic anemia. [4] Etiology: 1) blood losses from: a) gastrointestinal losses - gastritis & peptic ulcer disease - GI malignancy - varices - angiodysplasia - inflammatory bowel disease b) genitourinary losses - menstrual bleeding - iron loss with each menstrual period is about 20 g c) blood donation - each unit of blood contains 250 mg of iron d) phlebotomy e) chronic hemoptysis f) hemodialysis 2) malabsorption a) achlorhydria - atrophic gastritis - proton pump inhibitors (RR=2.5) [19] - H2-receptor antagonists (RR=1.6) [19] b) surgery - gastric - small bowel c) high intestinal transit time d) celiac disease e) parasitic infection by hookworms f) Helicobacter infection 3) nutritional deficiency - infants with unsupplemented milk - vegan or vegetarian diet 4) pregnancy: iron loss is 500-1000 mg in pregnancy 5) lactation 6) idiopathic pulmonary hemosiderosis Pathology: 1) depletion of iron stores 2) compromised iron delivery to sites of utilization 3) iron-deficient erythropoiesis Clinical manifestations: 1) most patients asymptomatic 2) symptoms are those common to all forms of anemia a) fatigue b) exercise intolerance c) headache d) dizziness e) faintness f) exertional dyspnea g) angina pectoris h) palpitation i) claudication j) tachycardia k) cold intolerance 3) symptoms develop only when Hgb < 7 g/dL if anemia is chronic unless coexistent pulmonary or cardiovascular disease 4) pica, pagophagia 5) skin & conjunctival pallor 6) cheilosis, cheilitis, stomatitis, glossitis 7) hair loss [4] 8) brittle or "spoon nails" (koilonychia) 9) restless legs syndrome 10) iron-deficiency may cause cognitive impairment/poor performance on standardized tests in children & adolescents even in the absence of anemia [3] Laboratory: 1) complete blood count (CBC) a) red blood cell (RBC) count - < 5 X10E12/L in iron deficiency; - > 5 X10E12/L in thalassemia - anemia precedes hypochromia & microcytosis b) red cell distribution width (RDW) - > 16 in iron deficiency - < 16 in thalassemia c) mean corpuscular volume (MCV) - decreased in iron-deficiency anemia (< 80 fL) - may be normal (33% of patients) - when iron stores are adequate - mild iron deficiency anemia - patients with liver disease - in association with inflammation [2] - combined iron & B12 or folate deficiency d) mean corpuscular hemoglobin is decreased (MCHC < 32 g/dL) e) platelet count is often elevated (may exceed 1,000,000/uL early in disease) 2) reticulocyte count: inappropriately low for degree of anemia 3) peripheral smear: anemia which precedes morphological changes [2] a) microcytosis b) poikilocytosis c) anisocytosis d) hypochromia 4) iron studies: abnormalities precede anemia [2] a) microcytic anemia in menstruating women precludes need to prove iron deficiency provided prior normal blood hemoglobin (MKSAP19) b) serum iron - decreased in iron-deficiency anemia (< 60 ug/dL) - decreased with compromised delivery of iron to sites of utilization (see pathology) - low serum iron also occurs in: - acute inflammation - chronic inflammation - malignancy - infection c) total-iron binding capacity (TIBC) - usually increased (> 400 ug/dL) in iron-deficiency anemia [2] - largely reflects transferrin concentration - increased with compromised delivery of iron to sites of utilization (see pathology) - may be normal or low in: - inflammation - infection - malignancy d) serum ferritin - earliest marker of iron deficiency - low serum ferritin (<12-15 ng/mL) indicates iron-deficiency - ferritin is an acute-phase reaction, thus high or normal levels may mask iron-deficiency; ferritin is elevated in: - infection - inflammatory conditions - hepatic disorders - malignancy - chronic renal failure - serum ferritin > 100 ng/mL rules out iron deficiency even with inflammation [2] - low serum ferritin in the absence of anemia - may be associated with fatigue in menstruating women - symptoms may respond to iron supplementation [7] e) transferrin saturation - measured by serum iron/total-iron binding capacity (TIBC) - <9% is consistent with iron deficiency - <15% is consistent with iron deficiency [1] - >15% is consistent with anemia of chronic disease - 9-15% requires a bone marrow biopsy to distinguish iron deficiency from anemia of chronic disease - decreased with compromised delivery of iron to sites of utilization (see pathology) f) serum hepcidin levels are low [2,12,13] g) serum transferrin receptor is increased (not routine) 5) fecal occult blood 6) urinalysis: - examine for hematuria, hemoglobinuria, hemosiderinuria 7) serum free erythrocyte protoporphyrin (FEP) not routine a) increased in: - iron deficiency - anemia of chronic disease - heavy metal exposure b) normal in: - thalassemia - sideroblastic anemia 8) resistance to oral iron - H pylori antigen in stool (prior to trial of different form of oral iron) [2] cites [16] - H pylori serology (not mentioned in [2]) - testing for celiac disease if white [2] - tissue transglutaminase IgA in serum - gliadin antibody in serum 9) bone marrow biopsy (not routine) a) gold standard for diagnosis of iron deficiency b) decreased absent stainable iron indicates iron deficiency c) adequate iron stores in the bone marrow rule out iron deficiency unless the patient has recently received iron through supplementation or transfusion 10) osmotic fragility [28] 11) lead in blood [28] * also see ARUP consult [26] Special laboratory: 1) upper GI endoscopy* - upper GI bleed - suspected celiac disease (obtain duodenal biopsies) - telangiectasias (hereditary hemorrhagic telangiectasias) [2] - prior to colonoscopy if the source of bleeding is unknown 2) colonoscopy* - if upper GI endoscopy is negative - prior to upper GI endoscopy if lower GI bleeding is anticipated - radiation proctitis [30] 3) also see upper gastrointestinal hemorrhage* * in men & non-menstruating women, GI bleed is the presumed cause of iron deficiency until proven otherwise; upper GI endoscopy & lower GI endoscopy (bidirectional endoscopy) indicated [2] * repeat upper GI endoscopy & lower GI endoscopy if source of iron loss (bleeding) not found & initial studies of low quality [2] * ref [2] suggests colonoscopy prior to upper GI endoscopy Radiology: - see upper gastrointestinal hemorrhage Complications: - complications of hypoxemia - myocardial ischemia - preoperative anemia associated with increased perioperative mortality & perioperative morbidity due to increased risk for need of blood transfusion [1] - dysphagia with solid food due to esophageal webs [28] - atrophic gastritis [28] - pseudotumor cerebri, papilledema, ncreased intracranial pressure - corrected with iron therapy [28] - impaired immune function [28] - hypothyroidism [28] Differential diagnosis: 1) iron deficiency accounts for the majority of all hypochromic microcytic anemias 2) thalassemia 3) hemoglobinopathy 4) anemia of chronic disease 5) sideroblastic anemia a) lead b) isoniazid c) pyrazinamide 6) Plummer-Vinson syndrome Management: 1) treat underlying cause of iron deficiency - ensure dietary iron - uncomplicated asymptomatic patients with negative upper GI endoscopy & negative colonoscopy can be treated empirically with iron supplementation rather than video capsule endoscopy [2] 2) transfusion if indicated a) symptomatic b) risk of damage to vital organ 3) iron supplementation (see iron replacement therapy) a) FeSO4 325 mg (65 mg of elemental iron) - QD or QOD dosing [2] on an empty stomach for 6 months - side effects in 25% - least expensive - QOD dosing (60 mg iron) associated with better absorption than QD, BID or TID dosing in iron-deficient women [21] b) QD or QOD dosing in elderly 1] GRS11 favors QOD dosing [25] 2] ferrous gluconate 300 mg (36 mg of elemental iron) QD in elderly 3] 15 mg elemental iron PO QD in the elderly [5,18] 4] ferrous gluconate not any better tolerated than FeSO4 [2] (this claim not consistent with other literature) c) children: 3 mg/kg of elemental iron QD as ferrous sulfate drops [20] d) iron uptake may be saturable - 15-20 mg/day of elemental iron can be as effective as higher doses [10] e) do not use ascorbate to facilitate absorption of iron [2] - ascorbate increases iron absorption [10,25] - 500-unit vitamin C supplements along with their iron once daily [28] - this claim is not consistent with other literature - ascorbate may result in GI bleed via Fenton reaction f) adding vitamin C to iron does not improve blood hemoglobin [27] g) lack of response to iron supplementation suggests malabsorption - celiac disease or other cause, see etiology h) avoid tea & coffee [28] (of questionable benefit) 4) parenteral iron (iron sucrose) a) reserved for patients not candidates for oral therapy - hemodialysis [2] b) patients with comorbid anemia of chronic renal failure [25] c) reduces need for transfusion relative to oral iron [9] d) iron dextran (imferon), iron sucrose e) ferric gluconate for dialysis patients f) four 200-mg infusions of iron sucrose over 2-weeks may reduce fatigue in women with low serum ferritin (< 15 ng/mL) but without anemia [6] g) rarely anaphylaxis will occur with parenteral iron 5) maximal reticulocyte response occurs in 7-10 days of initiation of iron supplementation 6) hemoglobin should normalize within 2 months 7) continue iron for 3-4 months after normalization of hemoglobin to replenish iron stores Follow-up: 6-8 weeks to assess response to therapy. Screening not recommended - evidence insufficient to recommend for or against screening of asymptomatic infants age 6-24 months or asymptomatic pregnant women [11]

Interactions

disease interactions

Related

iron replacement therapy

General

hypochromic anemia hypoplastic anemia iron-deficiency microcytic anemia

References

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