Guidelines Guidelines for the management of iron deficiency anaemia Andrew F Goddard,1 Martin W James,2 Alistair S McIntyre,3 Brian B Scott,4 on behalf of the British Society of Gastroenterology 1Digestive Diseases Centre, ABSTRACT lower GI investigation should be reserved for those Royal Derby Hospital, Derby, UK 2 Background aged 50 years or older, those with symptoms Nottingham Digestive Diseases < e suggesting gastrointestinal disease, and those with Centre, NIHR Biomedical Iron deficiency anaemia (IDA) occurs in 2 5% of adult Research Unit, Nottingham, UK men and postmenopausal women in the developed a strong family history of colorectal cancer (B). 3Department of world and is a common cause of referral to < Upper and lower GI investigation of IDA in post- Gastroenterology, Wycombe gastroenterologists. Gastrointestinal (GI) blood loss gastrectomy patients is recommended in those over Hospital, High Wycombe, UK 4 from colonic cancer or gastric cancer, and malab- 50 years of age (B). Department of < Gastroenterology, Lincoln sorption in coeliac disease are the most important In patients with iron deficiency without anaemia, County Hospital, Lincoln, UK causes that need to be sought. endoscopic investigation rarely detects malignancy. Defining iron deficiency anaemia Such investigation should be considered in patients Correspondence to < The lower limit of the normal range for the laboratory aged >50 after discussing the risk and potential Brian B Scott, Department of benefit with them (C). Medicine, Lincoln County performing the test should be used to define anaemia (B). < < Hospital, Lincoln LN2 5QY, UK; Any level of anaemia should be investigated in the Only postmenopausal women and men aged [email protected] presence of iron deficiency (B). >50 years should have GI investigation of iron < The lower the haemoglobin the more likely there is to deficiency without anaemia (C). Received 28 September 2010 be serious underlying pathology and the more urgent < Rectal examination is seldom contributory, and, in the Accepted 20 March 2011 absence of symptoms such as rectal bleeding and Published Online First is the need for investigation (B). 11 May 2011 < Red cell indices provide a sensitive indication of iron tenesmus, may be postponed until colonoscopy. deficiency in the absence of chronic disease or < Urine testing for blood is important in the examination haemoglobinopathy (A). of patients with IDA (B). < Haemoglobin electrophoresis is recommended when Management microcytosis and hypochromia are present in patients < All patients should have iron supplementation both to of appropriate ethnic background to prevent unnec- correct anaemia and replenish body stores (B). essary GI investigation (C). < Parenteral iron can be used when oral preparations are < Serum ferritin is the most powerful test for iron not tolerated (C). deficiency (A). < Blood transfusions should be reserved for patients Investigations with or at risk of cardiovascular instability due to the < Upper and lower GI investigations should be considered degree of their anaemia (C). in all postmenopausal female and all male patients where IDA has been confirmed unless there is a history of significant overt non-GI blood loss (A). SCOPE < All patients should be screened for coeliac disease (B). These guidelines are primarily intended for Western < If oesophagogastroduodenoscopy (OGD) is performed gastroenterologists and gastrointestinal (GI) as the initial GI investigation, only the presence of surgeons, but are applicable for other doctors seeing advanced gastric cancer or coeliac disease should patients with iron deficiency anaemia (IDA). They deter lower GI investigation (B). are not designed to cover patients with overt blood < > In patients aged 50 or with marked anaemia or loss or those who present with GI symptoms. GI a significant family history of colorectal carcinoma, symptoms or patients at particular risk of GI lower GI investigation should still be considered even if disease should be investigated on their own merits. coeliac disease is found (B). < Colonoscopy has advantages over CT colography for investigation of the lower GI tract in IDA, but either is INTRODUCTION acceptable (B). Either is preferable to barium enema, IDA occurs in 2e5% of adult men and post- which is useful if they are not available. menopausal women in the developed world1 2 and < Further direct visualisation of the small bowel is not is a common cause of referral to gastroenterologists necessary unless there are symptoms suggestive of (4e13% of referrals).3 While menstrual blood loss is small bowel disease, or if the haemoglobin cannot be the most common cause of IDA in premenopausal restored or maintained with iron therapy (B). women, blood loss from the GI tract is the most < In patients with recurrent IDA and normal OGD and common cause in adult men and postmenopausal e colonoscopy results, Helicobacter pylori should be women.4 9 Asymptomatic colonic and gastric eradicated if present. (C). carcinoma may present with IDA, and seeking < Faecal occult blood testing is of no benefit in the these conditions is a priority in patients with IDA. investigation of IDA (B). Malabsorption (most commonly from coeliac < All premenopausal women with IDA should be disease in the UK), poor dietary intake, blood screened for coeliac disease, but other upper and donation, gastrectomy and use of non-steroidal Gut 2011;60:1309e1316. doi:10.1136/gut.2010.228874 1309 Guidelines anti-inflammatory drugs (NSAIDs) are common causes of IDA, that any level of anaemia should be investigated in the presence and there are many other possible causes (table 1). IDA is often of iron deficiency. Furthermore, it is recommended13 that men multifactorial. Its management is often suboptimal, with most with Hb concentration <12 g/dl and postmenopausal women patients being incompletely investigated or not investigated at with Hb concentration <10 g/dl should be investigated all.10 11 Dual pathologydthat is, the presence of a significant more urgently, since lower levels of Hb suggest more serious cause of bleeding in both upper and lower GI tractsdmay occur disease (A). e in 1e10% of patients or more4 9 and should be increasingly considered the older the patient. Iron deficiency Modern automated cell counters provide measurements of the fi DEFINING IDA changes in red cells that accompany iron de ciency: reduced mean d d Anaemia cell Hb (MCH) hypochromia and increased percentage of fi hypochromic red cells and reduced mean cell volume (MCV)d The World Health Organization de nes anaemia as a haemo- 14 globin (Hb) concentration below 13 g/dl in men over 15 years of microcytosis. The MCH is probably the more reliable because it fl age, below 12 g/dl in non-pregnant women over 15 years of age, is less in uenced by the counting machine used and by storage. and below 11 g/dl in pregnant women.1 The diagnostic criteria Both microcytosis and hypochromia are sensitive indicators of e fi for anaemia in IDA vary between published studies.4 9 The iron de ciency in the absence of chronic disease or coexistent fi 15 normal range for Hb also varies between different populations in vitamin B12 or folate de ciency. An increased red cell distribu- the UK. Therefore it is reasonable to use the lower limit of the tion width will often indicate coexistent vitamin B12 or folate fi normal range for the laboratory performing the test to define de ciency. Microcytosis and hypochromia are also present in anaemia (B). many haemoglobinopathies (such as thalassaemia, when the There is little consensus as to the level of anaemia that MCV is often out of proportion to the level of anaemia compared fi requires investigation. The NHS National Institute for Health and with iron de ciency), in sideroblastic anaemia and in some cases Clinical Excellence referral guidelines for suspected lower GI of anaemia of chronic disease. Hb electrophoresis is recommended cancer suggest that only patients with Hb concentration <11 g/dl when microcytosis is present in patients of appropriate ethnic in men or <10 g/dl in non-menstruating women be referred.12 It background to prevent unnecessary GI investigation (C). fi has been suggested that these cut-off values miss patients with The serum markers of iron de ciency include low ferritin, low colorectal cancer, especially men.13 It is therefore recommended transferrin saturation, low iron, raised total iron-binding capacity, raised red cell zinc protoporphyrin, and increased serum transferrin receptor (sTfR). Serum ferritin is the most powerful test for iron deficiency in the absence of inflammation Table 1 Pathological contributors to iron deficiency anaemia in the UK with prevalence as percentage of (A). The cut-off concentration of ferritin that is diagnostic varies e m 16 17 total4 9 between 12 and 15 g/l. This only holds for patients fl Contributor Prevalence without coexistent in ammatory disease. Where there is inflammatory disease, a concentration of 50 mg/l or even more Occult GI blood loss may still be consistent with iron deficiency.1 The sTfR concen- Common tration is said to be a good marker of iron deficiency in healthy e Aspirin/NSAID use 10 15% subjects,18 but its utility in the clinical setting remains to be Colonic carcinoma 5e10% proven. Several studies have shown that the sTfR/log serum Gastric carcinoma 5% 10 ferritin ratio provides superior discrimination to either test on its Benign gastric ulceration 5% own, particularly in chronic disease.19 Angiodysplasia 5% fi fi Uncommon Further tests to con rm iron de ciency are occasionally Oesophagitis 2e4% necessary. Estimation of iron concentration in bone marrow by 14 ‘ ’ Oesophageal carcinoma 1e2% the histochemical method may distinguish between true iron fi Gastric antral vascular ectasia 1e2% de ciency and other chronic disorders in which there is impaired e Small bowel tumours 1e2% release of iron from cells of the monocyte macrophage system Cameron ulcer in large hiatus hernia <1% (previously known as reticuloendothelial cells), but is subjective Ampullary carcinoma <1% and seldom performed.