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Anemia.ppt
- 1. Anemia CBC, retic count Hypoproliferative Retics normal or increased
- 2. Hypoproliferative Clues from morphology microcytic, normocytic, or macrocytic poikilocytosis anisocytosis nucleated red cells target cells Howell-Jolly bodies hypersegmented polys Marrow damage > Infiltration; fibrosis > Aplasia > Myelodysplasia > Drug or radiation injury Iron deficiency B12 deficiency Folate deficiency Stimulus > Inflammation > Endocrine defect > Renal disease Hypersplenism
- 3. Retics normal or increased Hemorrhage and Hemolysis Blood loss Hemolysis > Antibody-mediated > Membrane defect > Metabolic defect > Red cell fragmentation Hemoglobinopathy Clues from morphology microcytic, normocytic, or macrocytic red cell fragmentation red cell clumping nucleated red cells target cells
- 4. IRF = immature reticulocyte fraction = immature retics / total retics HLR% = high light scatter retics = Retics% x IRF Foucade, Belaouni. Lab Hematol 1999; 5:153-8
- 5. IRF and Anemia Foucade, Belaouni. Lab Hematol 1999; 5:153-8
- 16. Gut lumen Fe+++ Fe++ Heme Fe Enterocyte DMT1 Ferritin Fe ++ Fe +++ MTP1 Plasma transferrin Enterocyte precursor Hepcidin Transferrin Receptor HFE Regulation of iron absorption
- 17. •Marrow iron stores •1 - 3+ •0 - 1+ •0 •0 •Ferritin •50 - 200 •<20 •<15 •0 •TIBC •300 - 360 •>360 •>380 •>400 •Serum iron •50 - 150 •50 - 150 •<50 •<30 •Red cells •normal •normal •normal •microcytic, hypochromic Iron stores Erythron iron
- 19. Gastrointestinal absorption 1 mg/day Storage iron Liver, RES 1 gram Functional iron Blood, marrow, myoglobin 2 grams Plasma transferrin 2 mg Daily physiologic loss 1 mg
- 20. Serum iron after oral iron in patients with iron deficiency WH Crosby, Arch Int Med; circa 1970 20 40 60 80 1 2 3 4 Serum iron Hours
- 21. Kaltwasser, Gottschalk. Kidney Int. 1999; 55(suppl): S49 - S56 Serum ferritin and total body iron
- 22. Serum transferrin receptor Storage iron = 107 mg Storage iron = 335 mg Storage iron = 1,102 mg Serial measurement of sTfr during phlebotomy in 3 individuals Goodnough, Skikne, Brugnara. Blood, 2000; 96: 823 - 833
- 23. Ratio of serum transferrin receptor to ferritin as a measure of total body iron Cook, Flowers, Skikne. Blood 2003; 101: 3359 - 64
- 24. Erythropoietin response in iron deficiency Spivak JL. Lancet 2000; 355:1707 - 12
- 25. Schreiber, Howalt, et at. NEJM 1996; 334: 619 - 23 Controls = normal volunteers and patients with traumatic blood loss Serum erthyropoietin levels in patients with inflammatory bowel disease
- 26. Schreiber, Howalt, et at. NEJM 1996; 334: 619 - 23 IL-1 and anemia in patients with inflammatory bowel disease
- 27. Schreiber, Howalt, et at. NEJM 1996; 334: 619 - 23 Treatment with oral iron ± rEPO in patients with inflammatory bowel disease
- 28. Anemia of chronic disease Inflammation Tissue necrosis Infection Neoplasia Congestive heart failure Acute myocardial infarction
- 29. Anemia of chronic disease Typical lab findings: Serum iron < 50 TIBC < 150 Normochromic or hypochromic red cells Normal ferritin Normal serum transferrin receptor
- 30. Anemia of chronic disease Mechanisms: blunted erythropoietin response diminished response of erythroid precursors to erythropoietin decreased delivery of iron from RES, increased intracellular ferritin in macrophages decreased gastrointestinal iron absorption
- 31. Anemia of chronic disease Mediators: IL-1 IL-6 g-interferon TNF-a
- 32. Mortality and initial hematocrit in PRAISE Mozaffarian, Levy, et al. J Am Coll Cardiol 2003; 41(11): 1933 - 9 Prospective randomized amlodipine survival evaluation 1130 patients 15 month follow-up Results adjusted using multivariant Cox model for age, gender, diabetes, smoking, heart failure etiology, EF, NYHA class, systolic BP, WBC, creatinine, and 18 additional factors
- 33. Mortality and initial hematocrit in PRAISE Mozaffarian, Levy, et al. J Am Coll Cardiol 2003; 41(11): 1933 - 9
- 34. Prospective, randomized study of erythropoietin and i.v. iron in patients with CHF Silverberg DS, Wexler D, et al. J Am Coll Cardiol 2001; 37: 1775 - 80 32 patients NYHA Class III or IV LVEF < 40% Hgb 10 - 11.5 Randomized Sq epo twice a week i.v. iron sucrose weekly Continue standard therapy
- 35. Prospective, randomized study of erythropoietin and i.v. iron in patients with CHF Silverberg DS, Wexler D, et al. J Am Coll Cardiol 2001; 37: 1775 - 80 NYHA class LVEF Days in hospital Hgb Ferritin Creatinine epo and i.v. iron observation + 48% + 5 % - 79% 10.312.9 221 366 1.7 1.7 - 11% - 5 % + 28% 10.910.8 264 283 1.4 1.8 After 8 months:
- 36. Anemia of chronic disease In IBD study and in CHF study response to treatment was not predicted by: serum erythropoietin serum iron ferritin
- 37. Goodnough, Skikne, Brugnara. Blood, 2000; 96: 823 - 833 Effectiveness of treatment with erythropoietin
- 38. Safety of intravenous iron Faich, Strobos. Am J Kidney Dis 1999: 33(3):464-70 Sodium ferric gluconate in sucrose (Ferrlecit) Available in Europe > 30 years 2.7 x 106 doses/year in Germany + Italy in 1995 Iron dextran (Imferon until 1992, InFed since 1992) 3 x 106 doses/year in US in 1996
- 39. Safety of intravenous iron Faich, Strobos. Am J Kidney Dis 1999: 33(3):464-70 Reported severe adverse reactions (1976 - 1996): SFGS 3.3 severe allergic reactions/106 doses, no fatalities ID 8.7 severe allergic reactions/106 doses, 31 fatalities
- 40. Safety of intravenous iron Faich, Strobos. Am J Kidney Dis 1999: 33(3):464-70 Other theoretical risks: iron overload sepsis accleration of athersclerosis
- 41. Recombinant human erythropoietin is approved only for treatment of anemia caused by renal failure or by cancer treatment and for certain hematologic malignancies. Sodium ferric gluconate in sucrose is approved only for treatment of anemia in patients on hemodialysis and for patients who have had a severe reaction to iron dextran. Medicare warning :(