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Iron - Part 2 Practical Aspects. Iron deficiency Hereditary hemochromatosis. 1. What is your approach to the history and physical examination?. Anemia . Check MCV. MCV 80 - 100 Normocytic anemia. MCV > 100 Macrocytic anemia. MCV < 80 Microcytic anemia. Defective synthesis of:. Fe.
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Iron - Part 2Practical Aspects Iron deficiency Hereditary hemochromatosis
1. What is your approach to the history and physical examination?
Anemia Check MCV MCV 80 - 100 Normocytic anemia MCV > 100 Macrocytic anemia MCV < 80 Microcytic anemia Defective synthesis of: Fe Globin chains thalassemias HbE Heme iron deficiency anemia anemia of chronic disease sideroblastic anemia lead poisoning
Case 1 Question 1: discussion • iron deficiency most likely • symptoms suspicious for lower GI tract pathology. • ask about melena, hematochezia, weight loss, family history of colon ca • still ask about chronic inflammatory diseases • rectal exam indicated
2. What other investigations are appropriate? • serum ferritin 12 ug/L (30-400) • iron 8 umol/L (10-28) • TIBC 80 umol/L (38-76) • transferrin sat. 10 % (20-55) • Conclusion: Iron deficiency anemia
Look for the cause • could consider stool for occult blood • but if negative, would you be reassured? • investigate the lower GI tract: colonoscopy
3. How would you replace iron? • oral is best • aim for 200 mg elemental iron/day, of which only 5-20% is absorbed in the iron-deficient state • 1 mg elemental iron ≠ 1 mg ferrous salts • avoid enteric coated iron preparations • adverse effects • GI • iron overload
4. How long would you treat for? • Continue until iron stores are replete (ie. ferritin well into normal range) • Usually 4 to 6 months, assuming no ongoing excessive iron losses. • Must follow patients on iron therapy • assess the adequacy of therapy • avoid iatrogenic iron overload • This may occur simultaneously with the management of the underlying cause
5. What is the expected response? • reticulocytosis within 5 to 10 days • anemia halfway corrected by 3 weeks* • hemoglobin corrected within 2 months* • ferritin will correct after the anemia has resolved *assuming cause of iron deficiency has been corrected
Causes of failure of oral iron replacement • poor compliance • poor absorption of oral iron • ongoing negative iron balance • wrong diagnosis, or co-existing 2nd cause of anemia is present
6. What if the patient is intolerant to oral iron? • Iron dextran (IM) • risk of anaphylaxis (0.5 – 1%) • skin tattoo • Iron sucrose or gluconate (IV)
Classic hereditary hemochromatosis • autosomal recessive • usually caused by homozygosity of C282Y mutation of HFE gene • prevalent • cellular mechanism still fuzzy • C282Y impairs HFE interaction with transferrin receptor (TfR1) • increases shift of iron into plasma from enterocytes
Endorgan damage due to iron deposition in hereditary hemochromatosis • liver • cirrhosis • endocrine glands (pancreas, pituitary) • diabetes • hypogonadism (impotence, amennorhea) • heart • cardiomyopathy • joints • arthropathy • skin • bronze pigmentation Classic triad (cirrhosis, diabetes, bronze skin) now rarely seen
Symptoms • asymptomatic • fatigue • symptoms relating to endorgan damage
Limited penetrance of homozygosity for C282Y abnormal liver, glucose, endocrine, cardiac tests organ damage high tissue iron high plasma iron mutant HFE
Management • lifelong phlebotomy program • keep ferritin < 50 ug/L • genetic counselling • dietary counselling • avoid/minimize EtOH • avoid iron, megadose vitamin C • treat complications, if present • surveillance for new complications
Prognosis • Phlebotomy initiated early (before endorgan damage) is compatible with normal survival • Established endorgan damage usually permanent, but progression can be slowed
Iron - Part 2Practical Aspects Iron deficiency Hereditary hemochromatosis