Seminars for the 5th year summer term Prof. MUDr. Jiří Horák Hematology 2 Iron Deficiency Anemia Stages of iron deficiency normal iron stores serum ferritin (ng/ml) transferrin saturation (%) RBC morphology normal 50 – 200 negative iron balance ↓ < 20 irondeficient erythropoiesis ↓↓ < 15 iron deficiency anemia ↓↓↓ < 15 30 – 40 normal < 20 < 10 normal normal normal Causes of iron deficiency Increased demand for iron and/or hematopoiesis Rapid growth in infancy or adolescence Pregnancy Erythropoietin therapy Increased iron loss Chronic blood loss Menses Acute blood loss Blood donation Therapeutic phlebotomy Decreased iron intake, absorption, or use Inadequate diet Malabsorption (sprue, Crohn’s disease, resection) Acute or chronic inflammation Iron store measurements Iron stores serum ferritin (ng/ml) 0 < 15 1 – 300 mg 15 – 30 300 – 800 mg 30 – 60 800 – 1000 mg 60 – 150 1–2g > 150 iron overload > 500 – 1000 1/4 microcytic hypochromic Seminars for the 5th year summer term Prof. MUDr. Jiří Horák Treatment oral iron therapy: 200 – 300 mg elemental iron → absorption of up to 50 mg iron parenteral iron therapy (iron dextran – adverse effects, esp. anaphylaxis in 0.7%, iron gluconate – Ferrlecit safer) The amount of iron needed: Body weight (kg) x 2.3 x (15 – patient’s hemoglobin, g/dl) + 500 or 1000 mg (for stores) Anemia of acute and chronic disease One of the most common forms of anemia. Serum ferritin levels are often increased. Suppression of erythropoiesis by inflammatory cytokines (TNF, interferon beta and gamma, IL-1). Anemia of cancer is usually normocytic and normochromic. In rheumatoid arthritis or chronic infections, anemia is microcytic and hypochromic. Acute infection can produce a fall in hemoglobin levels of 2-3 g/dl within one or two days, which is largely related to hemolysis. Anemia of renal disease The level of the anemia correlates with the severity of the renal failure. Red cells are normocytic and normochromic. Reticulocytes are decreased. Cause: inadequate production of erythropoietin, reduction in red cell survival. Serum iron and ferritin levels are usually normal. In dialyzed patients iron deficiency may develop. Erythropoietin treatment: 50 – 150 U/kg three times a week subcutaneously. Megaloblastic anemias Cobalamin deficiency 1 inadequate intake (vegetarians) 2 malabsorption a. defective release of cobalamin form food gastric achlorhydria partial gastrectomy drugs that block acid secretion b. inadequate production of intrinsic factor pernicious anemia total gastrectomy c. disorders of teminal ileum tropical sprue 2/4 Seminars for the 5th year summer term Prof. MUDr. Jiří Horák nontropical sprue regional enteritis intestinal resection neoplasms and granulomatous diseases Folic acid deficiency 1 inadequate intake (alcoholics) 2 increased requirements pregnancy infancy malignancy chronic hemolytic anemias chronic exfoliative skin disorders hemodialysis 3 malabsorption tropical sprue nontropical sprue drugs (phenytoin, barbiturates) 4 impaired metabolism inhibitors of dihydrofolate reductase: methotrexate, trimethoprim, pyrimethamine alcohol Cobalamine deficiency Symptoms of anemia – weakness, vertigo, tinnitus, palpitations, angina. Anemia may be very severe but is well tolerated. Subicterus is common (high erythroid cell turnover in the marrow). Smooth and sore red tongue. Megaloblastosis of the intestinal epithelium → malabsorption. Neurologic manifestations: demyelination, axonal degenereation, neuronal death → numbness, paresthesia, weakness, ataxia. Disturbances of mentation up to frank psychosis. Pernicious anemia – absence of intrinsic factor from either atrophy of the gastric mucosa or autoimmune destruction of parietal cells. The incidence of pernicious anemia is increased in patients with other immunopathologic disease – thyrotoxicosis, myxedema, thyroiditis, hypoparathyroidism. Antiparietal cell antibody, or anti-IF antibody. Helicobacter pylori does not cause parietal cell destruction. Dg: macrocytosis > 100 fl, low reticulocyte count, leukocyte and platelet count may also be decreased. Neutrophils show hypersegmentation of the nucleus. Unconjugated bilirubin is increased. 3/4 Seminars for the 5th year summer term Prof. MUDr. Jiří Horák Iron absorption by the intestinal villous cell Intestinal lumen Fe+++ → Fe++ DMT-1 Villous cell Dcytb ferritin Fe++ ferroportin 1 hephaestin (IREG-1) Basolateral surface Fe++ Fe+++ bound to Tf 4/4