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
WHO/UNICEF/UNU. Iron deficiency anemia: Assessment, prevention and control. Report of a joint WHO/UNICEF/UNU consultation. Geneva; World Health Organisation, 1998
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
Impact of anaemia
“asymptomatic”
Reduced quality of life: equalling cancer1
Higher disease activity2: reduced hct & general well-being
Chronic fatigue
Impaired cognitive performance3
Reduced mood
Increased incidence of and morbidity from infectious diseases4
Thyroid dysfunction & impaired thermoregulation5
Pregnancy: preterm delivery, low birth weight, reduced neonatal health6
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 B12 / folate deficiency1
Haemolysis2
Myelodysplastic syndrome3
Drug-induced:
Thiopurine4
Sulfasalazine5
Methotrexate6
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
CRP
Vitamin B12
Folate
Haptoglobin
Lactate dehydrogenase
Creatinine
Reticulocyte count
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 uptake2
Impaired iron absorption3 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/dL1
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)
References: 1. Micromedex Healthcare Series, 2007. Thomson Healthcare Inc 2. 1. Kerr DN et al. Lancet 1958;489-492
Maximum absorption of elemental iron is 20mg per day
Concerns:
Side effects / intolerance2: 21-52%
Toxic reactive oxygen species
Slow response
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)
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
LMW iron dextran
Cosmofer
Iron sucrose Venofer
Iron carboxymaltose
Ferrinject
Iron isomaltose
Monofer
Blood
Maximum single dose
20mg/kg 200mg 1000mg (20mg/kg)
20mg/kg
Rapid infusion No Yes (bolus) Yes Yes
Test dose? Yes Initial No No
Iron concentration
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 deficiency1 Up-regulation of ferritin
Reduced transferrin
Inhibition of erythropoiesis2 IL-1 & TNF-α produce toxic radicals
damage erythropoietin-producing cells
Inhibition of differentiation/proliferation of erythroid precursors3 Interferon-α, -β, -γ, TNF-α and IL-1
Uptake and retention of iron in the reticulo-endothelial system4 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
Ferritin (μg/L) Transferrin
saturation
(%)
MCV
MCH
sTR Active
inflammation
No
inflammation
IDA <100 <30 <16 ↓ ↓ ↑
ACD >100 >100 <16 Normal Normal Normal
or ↓
Identifying the cause of anaemia
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
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