ESPEN Congress Cannes 03 Organised by the Israel Society for Clinical Nutrition Education and Clinical Practice Programme Session: On Nutrition and Haematology: Consumption and Coagulation Nutrition and Anemia Professor Miguel León-Sanz Madrid, Spain email mleon@h12o.es Hematopoiesis Proteins Minerals Fe, Cu Vitamins B 12, Folate ESPEN 03. For personal use only. 1
Iron deficiency Prevalence in developing countries: -70 %, but < % in industrialized countries Risk groups: children, menstruating and pregnant women, recent immigrants, low socioeconomic status. Prevalence of depleted iron stores and anemia in menstruating women in European countries Country Age Depleted iron stores Anemia Hemoglobin < 1 g/l Sweden 38 33 6.5 Denmark -50 17.2 2.8 Norway 18-48 21.8 4.1 UK 18-50 9 France -50 2.9 Northern Ireland 18-44 18.2 13.5 Public Health Nutr 01; 4:537-545 ESPEN 03. For personal use only. 2
Iron deficiency Prevalence in developing countries: -70 %, but < % in industrialized countries Risk groups: children, menstruating and pregnant women, recent immigrants, low socioeconomic status. Improvements: fortification, supplementation, dietary diversification, economic development, public health measures. Prevalence of high iron stores Author Age men & women % Men % Women % Garry 1983 > 60-y-o Milman 1990 85-y-o 13 Milman 1994 70-y-o 8.7 3.7 Cals 1994 > 60-y-o 22.3 16.6 Milman 1999 60-70-y-o.8.2 Fleming 01 67-96-y-o 9.2; (12.9Å Ä) 13.9 28.8 6 12.2 Ferritin > 0 µg/l; > 0 µg/l ESPEN 03. For personal use only. 3
Iron stores and Chronic Diseases? Cancer Elevated Iron Stores Diabetes Mellitus Heart Disease Iron supplements in elderly people living in western countries? Iron deficiency in HPN patients Prevalence: -55 % Malabsorption Blood losses Active Crohn s disease Surgery Menstruation Frequent phlebotomy blood loss ESPEN 03. For personal use only. 4
Iron status assessment in HPN patients Every 3 months for the 1st year Twice a year in stable patients As suggested by blood losses Iron-deficiency when Hemoglobin < 12 g/dl Hypochromia, microcytosis TIBC > 0 µg/dl Ferritin < ng/ml Biochemical Markers in Functional Iron Deficiency Ferritin (+) acute phase reactant Trasnferrin (-) acute phase reactant Soluble Transferrin receptor in patients with hyperproliferative erythropoiesis ESPEN 03. For personal use only. 5
Anemia of chronic disease Immune and inflammatory mediators Shortened red cell Survival Red cell production Ø Erythropoietin Production and Sensitivity Ø Eythropoiesis Impaired release of Reticuloendothelial iron Hypoproliferative erythopoiesis Low serum iron & normal or raised serum ferritin Assessment of Anemia of Chronic Disease Reticulocyte hemoglobin content (CHr) < 28 pg Ferritin < 0 ng/ml Soluble transferrin receptor (stfr) > 1.5 mg/l stfr/log ferritin ratio (stfr-f index) > 0.8 ESPEN 03. For personal use only. 6
Diagnostic plots for the identification of Iron Deficiency in anemic patients with and without APR (acute-phase reponse) APR No APR The stfr-f indices separating patients in the iron-repleted state from those in the iron-depleted state are 0.8 in patients with APR (left) and 1.5 in those without (right). Clin Chem 02; 48:66-76 Diagnostic plot indicating the correlation between the biochemically indicated Fe supply for erythropoiesis, and CHr CHr (pg) Iron repletion, normal erytrhopoiesis Functional ID in Fe-repleted state. Decreased Hb of red cells 1 2 4 Patients may have reduced Fe supply, but have not yet begun Fe-deficient erythropoiesis. Normal hemoglobinization of red cells Depletion of storage and functional Fe compounds Decreased hemoglobinization of red cells 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 stfr (mg/l)/ log ferritin (µg/l) 3 Clin Chem 02; 48:66-76 ESPEN 03. For personal use only. 7
Diagnostic plot indicating the correlation between the biochemically indicated Fe supply for erythropoiesis, and CHr CHr (pg) Iron repletion, normal erytrhopoiesis 1 Patients with ACD and CRA Hemodyalisis patients without functional ID 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 stfr (mg/l)/ log ferritin (µg/l) Clin Chem 02; 48:66-76 Diagnostic plot indicating the correlation between the biochemically indicated Fe supply for erythropoiesis, and CHr CHr (pg) Iron repletion, normal erytrhopoiesis Functional ID in Fe-repleted state. Decreased Hb of red cells 1 2 4 Patients may have reduced Fe supply, but have not yet begun Fe-deficient erythropoiesis. Normal hemoglobinization of red cells Depletion of storage and functional Fe compounds Decreased hemoglobinization of red cells 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 stfr (mg/l)/ log ferritin (µg/l) 3 Clin Chem 02; 48:66-76 ESPEN 03. For personal use only. 8
Diagnostic plot indicating the correlation between the biochemically indicated Fe supply for erythropoiesis, and CHr CHr (pg) 2 Patients may have reduced Fe supply, but have not yet begun Fe-deficient erythropoiesis. Normal hemoglobinization of red cells Tumor patients Nonanemic pts. with latent ID IDA patients after starting oral Fe therapy 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 stfr (mg/l)/ Hyperproliferative log ferritin (µg/l) erythropoiesis: Acute hemorrhage, Hemolytic anemia, 3rd-Trim pregnancies with stfr Clin Chem 02; 48:66-76 Diagnostic plot indicating the correlation between the biochemically indicated Fe supply for erythropoiesis, and CHr CHr (pg) Iron repletion, normal erytrhopoiesis Functional ID in Fe-repleted state. Decreased Hb of red cells 1 2 4 Patients may have reduced Fe supply, but have not yet begun Fe-deficient erythropoiesis. Normal hemoglobinization of red cells Depletion of storage and functional Fe compounds Decreased hemoglobinization of red cells 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 stfr (mg/l)/ log ferritin (µg/l) 3 Clin Chem 02; 48:66-76 ESPEN 03. For personal use only. 9
Diagnostic plot indicating the correlation between the biochemically indicated Fe supply for erythropoiesis, and CHr Iron-Deficient Anemia: Ø iron stores Æ Ø iron supply for erythropoiesis CHr (pg) Depletion of storage and functional Fe compounds Decreased hemoglobinization of red cells 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 stfr (mg/l)/ log ferritin (µg/l) 3 Clin Chem 02; 48:66-76 Diagnostic plot indicating the correlation between the biochemically indicated Fe supply for erythropoiesis, and CHr CHr (pg) Iron repletion, normal erytrhopoiesis Functional ID in Fe-repleted state. Decreased Hb of red cells 1 2 4 Patients may have reduced Fe supply, but have not yet begun Fe-deficient erythropoiesis. Normal hemoglobinization of red cells Depletion of storage and functional Fe compounds Decreased hemoglobinization of red cells 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 stfr (mg/l)/ log ferritin (µg/l) 3 Clin Chem 02; 48:66-76 ESPEN 03. For personal use only.
Diagnostic plot indicating the correlation between the biochemically indicated Fe supply for erythropoiesis, and CHr CHr (pg) 4 Functional ID in Fe-repleted state. Decreased Hb of red cells Anemia accompanying infection or inflammation or APR with CRA ß-thalasemia Combined state of ID/ACD 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 stfr (mg/l)/ log ferritin (µg/l) Clin Chem 02; 48:66-76 CHr (pg) Diagnostic plot indicating the correlation between the biochemically indicated Fe supply for erythropoiesis, and CHr rhuepo Iron repletion, normal erytrhopoiesis Functional ID in Fe-repleted state. Decreased Hb of red cells 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 rhuepo + IV Fe 1 2 4 Patients may have reduced Fe supply, but have not yet begun Fe-deficient erythropoiesis. Normal hemoglobinization of red cells Depletion of storage and functional Fe compounds Decreased hemoglobinization of red cells stfr (mg/l)/ log ferritin (µg/l) 3 Oral Fe Clin Chem 02; 48:66-76 ESPEN 03. For personal use only. 11
IV Iron administration in the longterm Parenteral Nutrition patient Maintenance therapy Patients are at risk for developing Fe deficiency because of limited dietary intake and blood losses -50 mg/month Trace elements solutions Oligoeleme ntos Grifols Addamel Fresenius Oligoplus Braun Decan Baxter Volume ml ml ml ml Se µg 60 31.6 24 70 Mo µg 19.2 Fe µg 1117 00 00 Zn µg 00 6600 30 000 Mn µg 0 274.7 550 0 Cu µg 00 1271 760 480 Cr µg 11.8.4 Fl µg 950 570 1450 Co µg 1.47 I µg 1 126.9 127 1.52 ESPEN 03. For personal use only. 12
IV Iron administration in the longterm Parenteral Nutrition patient Maintenance therapy Patients are at risk for developing Fe deficiency because of limited dietary intake and blood losses -50 mg/month Treatment of iron deficiency Risk of iron overload due to bypass of intestinal absorption regulation and limited ability to excrete excessive amounts of Fe Fe (mg)=2. x Weight (kg) x (Hb i Hb a ) Comparison of parenteral iron preparations Iron dextran (InFeD) Sodium ferric gluconate (Ferlecit) Iron sucrose (Venofer) Replacement dose Total dose 0-00 mg ClNa 0.9 % >4-6 h 1-0 mg 0 ml ClNa 0.9 % x 60 0-0 mg 0 ml ClNa 0.9 % > Test dose mg Not required Not required PN compatibility 0 mg/l in nonlipid PN Not studied Not studied Hypersensitivity reactions 8.7/ 6 31 deaths 3.3/ 6 No deaths No serious adverse events ESPEN 03. For personal use only. 13
Copper deficiency and anemia 14 cases of copper deficiency described in patients on HPN Effect of copper deficiency and supplementation on hematocrit in a patient on HPN Blood transfusion % 45 0 µg/dl 5 180 160 1 1 0 80 60 Hematocrit % Cu µg/dl 0 0 0 60 1 1 1 0 5 170 190 0 2 2 270 285 295 Cu supplementation JPEN 00; 24:361-366 ESPEN 03. For personal use only. 14
Copper deficiency and anemia 14 cases of copper deficiency described in patients on HPN Anemia, neutropenia + thrombocytopenia (3 cases) Anemia could be microcytic, normocytic or macrocytic, with low reticulocyte count In HPN patients with hyperbilirubinemia, it is advisable to measure serum Cu concentrations before it is Ø or withheld from PN solutions. Thereafter, frequent Cu measurement to adjust the frequency or amount of Cu administration Anemia and Enteral Nutrition Commercial enteral formulas provide the RDA for vitamins and minerals in 1-2 L of product Risk conditions: diluted commercial formulas poor compliance with administration of EN formula increased requirements, or preexistent deficiencies. Large discrepancies between the mineral levels stated by the manufacturers and those found on analysis Identical amounts of vitamins and minerals for different diseases ESPEN 03. For personal use only.
Anemia and Enteral Nutrition Normal plasma levels of vitamins, including folate and vitamin B12, in patients nourished with long-term enteral feeding using commercial formulas for over 6 months But low levels of folate, beta-carotene, vitamins A, C and E in IBD Anemia and neutropenia due to copper deficiency has also been described in patients on long-term enteral nutrition Conclusion Patients on long-term parenteral or enteral nutrition can develop anemia due to nutrient deficiency (Fe and Cu) Iron deficiency anemia should be distinguished from anemia of chronic disease: choose the best diagnostic parameters (CHr, adjusted ferritin, stfr-f index) When IV iron is needed, sodium ferric gluconate and iron sucrose have replaced the use of iron dextran In HPN patients with hyperbilirubinemia, repeated Cu measurements are recommended to adjust the frequency or amount of Cu administration ESPEN 03. For personal use only. 16
References Forbes GM, Forbes A. Micronutrient status in patients receiving Home Parenteral Nutrition. Nutrition 1997; 13:941-944. Khaodhiar L, Keane-Ellison M, Tawa NE, Thibault A, Burke PA, Bistrian BR. Iron deficiency anemia in patients receiving home total parenteral nutrition. JPEN 02;26:114-9. Fuhrman MP, Herrmann V, Masidonski P, Eby C. Pancytopenia after removal of copper from total parenteral nutrition. JPEN J Parenter Enteral Nutr 00; 24:361-6. Shenkin A, Fraser WD, McLelland AJ, Fell GS, Garden OJ. Maintenance of vitamin and trace element status in intravenous nutrition using a complete nutritive mixture. JPEN J Parenter Enteral Nutr 1987; 11:238-42. Thomas C, Thomas L. Biochemical markers and hematologic indices in the diagnosis of functional iron deficiency. Clin Chem 02; 48:66-76. ESPEN 03. For personal use only. 17
References Kumpf VJ. Update on Parenteral Iron Therapy. Nutr Clin Pract 03; 18:318-326. Yee J, Besarab A. Iron sucrose: the oldest iron therapy becomes new. Am J Kidney Dis 02; : 1111-1121. Abad-Lacruz A, Fernandez-Banares F, Cabre E, Gil A, Esteve M, Gonzalez- Huix F, Xiol X, Gassull MA. The effect of total enteral tube feeding on the vitamin status of malnourished patients with inflammatory bowel disease. Int J Vitam Nutr Res 1988;58(4):428-. Berner Y, Morse R, Frank O, Baker H, Shike M. Vitamin plasma levels in long-term enteral feeding patients. JPEN J Parenter Enteral Nutr 1989; 13:5-8. Shils ME, Baker H, Frank O. Blood vitamin levels of long-term adult home total parenteral nutrition patients: the efficacy of the AMA-FDA parenteral multivitamin formulation. JPEN J Parenter Enteral Nutr 1985; 9:179-88. ESPEN 03. For personal use only. 18