Oxford Inflammatory Bowel Disease & Hepatology MasterClass Managing Anaemia in IBD Dr Alex Kent Senior Research Fellow
Disclosures
WHO Classification of Anaemia Normal haemoglobin and haematocrit levels Population group Haemoglobin Haematocrit g/dl Mmol/L % Children 6 mo 5 years 11.0 6.83 33 Children 5-11 years 11.5 7.13 34 Children 12-14 years 12.0 7.45 36 Non-pregnant women 12.0 7.45 36 Pregnant women 11.0 6.83 33 Men 13.0 8.07 39 WHO/UNICEF/UNU. Iron deficiency anemia: Assessment, prevention and control. Report of a joint WHO/UNICEF/UNU consultation. Geneva; World Health Organisation, 1998
Impact of anaemia asymptomatic Reduced quality of life: equalling cancer 1 Higher disease activity 2 : reduced hct & general well-being Chronic fatigue Impaired cognitive performance 3 Reduced mood Increased incidence of and morbidity from infectious diseases 4 Thyroid dysfunction & impaired thermoregulation 5 Pregnancy: preterm delivery, low birth weight, reduced neonatal health 6 References: 1. Leitgeb C et al. Cancer 1994: 2535-2542 2. Schreiber S et al. NEJM 1996:619-623 3. Beard JL et al. Am J Clin Nut 2007:778-787 4. Basta SS et al. Am J Clin Nut1979: 916-925 5. Dillman E et al. Am J Physio 1980:R377-381 6. Allen LH et al. Am J Clin Nut 2000:1280S-4S
Causes of anaemia in IBD Iron Deficiency Anaemia Anaemia of Chronic Disease Vitamin B 12 / folate deficiency 1 Haemolysis 2 Myelodysplastic syndrome 3 Drug-induced: Thiopurine 4 Sulfasalazine 5 Methotrexate 6 References: 1. Fernandez-Banares F et al. Am. J. Gastroenterol 1989;84(7):744-8. 2. Bell DW et al. South Med. J., 1981;74(3):359-61. 3. Wang, Z et al. Dig. Dis. Sci.2008;53(7):1929-32. 4. Corominas H et al. Med. Clin. (Barc.) 2000;115(8):299-301 5. Dunn AM et al. Lancet 1981;2(8258):1288. 6. Bellaiche G et al. Gastroenterol. Clin. Biol. 1999;23(10):1102-3.
Screening bloods Full blood count MCV Serum ferritin Transferrin saturation Haptoglobin Lactate dehydrogenase Creatinine Reticulocyte count CRP Vitamin B 12 Folate
Distribution of iron in adults 3-4 kg iron in human body
Iron absorption Maximum absorption: 20mg per day
Iron deficiency anaemia Prevalence 45% 1 Causes: Blood loss 1 ml blood = 0.5 mg iron daily losses >4ml = iron deficiency Poor nutritional uptake 2 Impaired iron absorption 3 SB Crohn s disease References: 1. Gisbert JP et al. Am J Gastro 2008:1299-1307 2. Lomer MC et al. Br J Nutr 2004:141-148 3. Semrin G et al. Inflamm Bowel Dis 2006:1101-1106
Iron deficiency anaemia: Treatment Aims: Hb rise of 2g/dL in 4 weeks Normalisation of Hb, ferritin and TF saturation Greatest improvement in QoL at 11 12 g/dl 1 Options: Oral iron Parenteral iron References: 1. Crawford J et al. Cancer 2000:888-895.
Oral iron Iron requirements (Body weight (kg) x (target Hb* (g/dl) actual Hb) x 2.4) + mg iron for stores # *Target Hb: for body weight below 35 kg = 13 g/dl; for body weight 35 kg and above = 15 g/dl #Depot iron: for body weight below 35 kg = 15 mg/kg body weight; for body weight 35 kg and above = 500 mg
Oral iron (cont) Maximum absorption of elemental iron is 20mg per day Elemental iron content of iron salts Iron salt Dose Iron content (%) Iron content Cost Ferrous sulphate 200mg 30 65mg 1.07 (28) Ferrous fumarate 200mg 33 65mg 2.30 (84) Ferrous gluconate 300mg 11.6 35mg 1.93 (28) Concerns: Side effects / intolerance 2 : 21-52% Toxic reactive oxygen species Slow response References: 1. Micromedex Healthcare Series, 2007. Thomson Healthcare Inc 2. 1. Kerr DN et al. Lancet 1958;489-492
Parenteral iron Iron gluconate Less stable, leading to labile iron release higher risk of A/E Maximum dose 125mg Iron dextran (low molecular weight) Dextran-related anaphylaxis; test dose required Long infusion time; large doses Long time interval before bioavailibility Iron sucrose (venofer) 95% of iron utilised within 2-4 weeks Maximum dose 600mg/week in 200mg infusions Iron carboxymaltose (ferrinject) Rapidly infused (1000mg in 15 mins); no test dose Iron utilised within 6-9 days so lower risk of A/E
Summary of parenteral iron preparations Maximum single dose LMW iron dextran Cosmofer Iron sucrose Venofer Iron carboxymaltose Ferrinject 20mg/kg 200mg 1000mg (20mg/kg) Rapid infusion No Yes (bolus) Yes Yes Test dose? Yes Initial No No Iron concentration Iron isomaltose Monofer 20mg/kg Blood 50 mg/ml 20 mg/ml 50 mg/ml 100 mg/ml 200mg per unit Vial volumes 2 & 10 5 2 & 10 1, 5 & 10 Cost 7.97 / 39.85 9.35 19.10 / 95.50 16.95 / 84.75 / 169.50
Parenteral iron (cont.) Guidelines on the diagnosis and management of iron deficiency and anemia in inflammatory bowel disease. Gasche C et al. Inflamm Bowel Dis. 2007 Dec;13(12):1545-53. Statement 4A: The preferred route of iron supplementation in IBD is intravenous, even though many patients will respond to oral iron. Intravenous iron is more effective, better tolerated, and improves the quality of life to a greater extent than oral iron supplements. (Grade A)
Indications for intravenous iron Haemoglobin <10g/dL Intolerance to oral iron Poor response to oral iron Moderate-severe disease activity Concomitant treatment with erythropoietic agent Patient preference
Anaemia of Chronic Disease Causes: Functional iron deficiency 1 Up-regulation of ferritin Reduced transferrin Inhibition of erythropoiesis 2 IL-1 & TNF-α produce toxic radicals damage erythropoietin-producing cells Inhibition of differentiation/proliferation of erythroid precursors 3 Interferon-α, -β, -γ, TNF-α and IL-1 Uptake and retention of iron in the reticulo-endothelial system 4 Interferon-γ, TNF-α and IL-6 Hepcidin References: 1. Macdougall IC et al. BMJ 1992:225-226 2. Faquin WC et al. Blood 1992:1987-1994 3. Theurl I et al. Blood 2006:4142-4148 4. Weiss G et al. NEJM 2005:1011-1023
Iron absorption Maximum absorption: 20mg per day
Identifying the cause of anaemia Ferritin (μg/l) Active No inflammation inflammation Transferrin saturation (%) MCV MCH str IDA <100 <30 <16 ACD >100 >100 <16 Normal Normal Normal or
Take home message Ask carefully for symptoms of anaemia Anaemia should raise concerns about disease activity Oral iron only in mild anaemia and inactive disease Do not overtreat with oral supplements Early treatment Intravenous iron is preferable