Managing Anaemia in IBD Dr Alex Kent Senior Research Fellow - - PowerPoint PPT Presentation

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

• r ↓

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