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Case Report 1
Mr Murphy, a 70-year-old man, lives with his wife and is independent in all activities of daily living. He still drives and manages his own finances. He attended his GP for his annual ‘check-up’ and his Hb was noted to be 11.5g/dL with an MCV<80fl. His ferritin was low (20μg/L) with low iron stores. His family history was positive for colorectal cancer and he had not attended any bowel screening programmes. He denies any change in bowel habit or weight loss and has not noticed any haematuria, etc. He does complain of some reflux symptoms. He takes aspirin for his ‘health’ as he read about it in the paper. He also takes diclofenac regularly for knee pain. He had his haematinics and inflammatory markers checked, which were normal and coeliac antibodies were negative. He had an OGD, which showed erosive gastritis. His aspirin and NSAID therapy were stopped. H.pylori was negative. He was treated with a PPI b.d. for a month and repeat OGD showed resolution of symptoms.
Case Report 2
Mrs Murphy is a 92-year-old nursing home resident for the past five years. She has advanced dementia and is non-verbal, incontinent, and immobile. She requires assistance for all activities of daily living. She was noticed to be pale and short of breath at rest for the past few days. Blood tests were taken in the nursing home – Hb was 6.2g/dL. She was transferred to an acute hospital. She was tachypneic, with sO2 of 80 per cent. Cardiorespiratory exam showed pedal and sacral oedema, elevated jugular venous pressure (JVP) and creps to midzones B/L. ECG showed diffuse T-wave changes and some Q-waves in anterolateral leads. Routine labs showed a hypochromic microcytic anaemia with a Hb of 6g/dL, iron was 1.2, with normal B12 and folate levels. Renal function and liver function tests were within normal limits. PR exam demonstrated no mass but faecal occult blood (FOB) was positive. Abdomen was soft and non tender. She was treated with IV diuretics and transfused with two units of red cells. It was decided to proceed to CT abdomen and pelvis as it is a minimally invasive exam. This showed a right-sided colonic tumour with no apparent metastases. A discussion was had with Mrs Murphy’s family. It was explained that she very likely had cancer of her colon causing her blood loss. The goals of treatment would be palliative focusing on symptom control. An iron transfusion was given to replenish iron stores. While she was in hospital a medication review was done to relieve medication burden. Her nursing home and GP were informed of future treatment plans and Mrs Murphy was discharged two days later with community palliative care follow-up.
Anaemia is common in the older elderly patient. It should never be explained as a normal consequence of ageing. Epidemiological data have shown that the prevalence of anaemia increases with advancing age, with a marked increase after the age of 60. The prevalence of anaemia in the geriatric population has been extensively studied and is reported to range from 4.4-8 per cent depending on the population studied (community-dwelling healthy older people to nursing home residents.). One of the main issues in quantifying anaemia in the older adult is the wide range of ‘normal’ values for haemoglobin. As per World Health Organisation (WHO) guidelines, regardless of age, anaemia is defined as a Hb of <13g/dl for men and <12g/dl for women.
Iron deficiency is common in both anaemic and non-anaemic patients, ranging from 18-35 per cent of older elderly patients. The commonest cause is acute or chronic blood loss. The most common cause of anaemia in the geriatric population is anaemia of chronic disease. Bearing in mind that the older frailer patient usually has multi-morbid conditions – the cause of anaemia can be hard to interpret and other diagnoses such as chronic kidney disease and primary haematological conditions should be borne in mind.
Signs and symptoms
Anaemia in the older elderly patient can present with a number of symptoms, some specific to later life in the elderly cohort. Older patients may have more subtle symptoms and signs than younger patients. Fatigue, pallor, and dyspnoea on exertion are classical symptoms. Restless legs syndrome has been attributed to iron deficiency with improvement of symptoms on oral iron supplementation.
Anaemia has been shown to be an independent risk factor for hospitalisation and death in the older adult.
Severe anaemia (haemoglobin concentration 4-5g/dL) can lead to congestive heart failure, even in patients with no prior history of ischaemic heart disease. In the presence of heart disease, especially coronary artery disease, anaemia can worsen angina pectoris and can contribute to a high incidence of other cardiovascular complications.
Headaches, loss of concentration, and depression are all common neurological symptoms of anaemia in older patients. Anaemia has also been shown to be an independent risk factor for delirium, particularly in the post-operative phase.
In the older patient, anaemia can lead to decreased in physical function and an increased falls risk. A study of older women showed that a Hb <12g/dl was shown to have an adverse eaffect on physical function.
A detailed history should be taken. Special attention should be focused on gastrointestinal symptoms such as weight loss, dysphagia, altered bowel habit and bleeding per rectum. Genitourinary symptoms, such as haematuria or vaginal bleeding, should be looked as well as other potential causes such as epistaxis.
Serum ferritin is the best indicator of iron deficiency. However, serum ferritin increases with age. Mean ferritin has been shown to be as high as 130μg/L in men and 98μg/L in women over the age of 85 years. Ferritin has to be interpreted carefully as a normal or even high level in a patient with iron deficiency can arise secondary to chronic inflammation, malignancy or liver disease. In the patient over 65 years of age, a low ferritin is usually defined as <50μg/L. In contrast, in a younger adult the normal cut off for ferritin would be 18μg/L.
Iron studies including a low serum iron with an increased total iron binding capacity and a low per cent transferrin saturation could also point to iron deficiency, but are less non specific in older patients the elderly. Serum iron levels can also show diurnal variation. Microcytosis alone is also not diagnostic as iron deficiency can also present as a normochromic normocytic picture. However, it is a potential further marker of iron deficiency.
Serum transferrin receptor (sTfr) assay can be used to diagnose iron deficiency. This has been proven to reliably diagnose iron deficiency. It is inversely correlated with tissue iron stores. It can also be raised in the setting of haemolysis. It is expensive and not readily available.
While iron deficiency is classically the result of acute or chronic blood loss, malabsorption although rare can be implicated. Coeliac screen should be done on all patients. Folate and B12 levels should be assessed.
Bone marrow aspirate and Prussian blue staining for iron is the gold standard test to definitively diagnose iron deficiency. However, this is an invasive test and is very rarely required.
The commonest cause of iron deficiency is acute or chronic blood loss, as previously stated, usually from the GI tract. A history of haemorrhage is an unusual finding but if present, this should guide subsequent investigations – eg, haematuria = cystoscopy, post-menopausal bleeding = hysteroscopy.
Common causes include – occult blood loss from GI tract (malignancy (gastric/colon), angiodysplasia, gastric ulceration, colonic polyps, NSAID use, inflammatory bowel disease).
Rarer causes include – coeliac disease, previous gastrectomy resulting in malabsorption, intestinal telangiectasia, lymphoma, small bowel malignancies.
In patients for whom there is no obvious cause, endoscopy is the investigation of choice.
OGDs are well tolerated even in advancing age. Sedation is minimal with low complication risk. OGDs have a high yield in older patients with iron deficiency with or without anaemia. A study looking at GI investigations in hospitalised patients over 70 years of age who were iron deficient showed that a potential upper GI tract lesion was found in 49 per cent of iron deficient anaemic patients and in 56 per cent of iron deficient non-anaemic patients. Esophagitis, erosive gastritis, and duodenitis were the most common causes in both groups. Of note, three patients in the non- anaemic group (3/55) were diagnosed with an upper GI malignancy.
Colonoscopy should be done in patients where no cause is found on OGD. Colonoscopy allows for biopsy and in some cases curative treatments (such as polypectomy). It has now superseded barium enemas as the examination of choice for colonic symptoms. Colonoscopies are often viewed as very invasive examinations with poor diagnostic yield due to poor preparation of bowel. Other concerns include dehydration, sedation risks, and poor patient tolerance. A UK study in 2005 audited 2,000 colonoscopies – half in those over the age of 65 years, with a median age of 75, while the control group had a median age of 54. Completion rates were similar in both groups. The older group had a higher diagnostic yield and complications were the same in both groups. In a retrospective case series looking at barium enemas it was found that poor preparation in 51 per cent of patients lead to an inadequate diagnostic exam, and they have also been shown to miss a substantial number of polyps >10mm in size. It is important to note that concomitant upper and lower GI pathology can occur in the same patient. Significant iron deficiency anaemia should not be blamed on trivial upper GI pathology such as mild gastritis.
Treating the underlying cause should prevent future iron loss.
In the case of gastric ulceration, H.pylori eradication should be completed if present with follow up endoscopy to ensure resolution. Medications should also be reviewed, eg, NSAID therapy, aspirin/anticoagulants (addition of PPI cover), prednisolone, SSRIs, cholinesterase inhibitors and bisphosphonates to name a few common in this population.
In the setting of colorectal cancer, it has been shown in multiple population based studies that older patients are more often not staged correctly, undergo fewer elective operations and are less likely to receive adjuvant chemotherapy and/or radiotherapy than their younger counterparts. In planned elective surgery in the older population, long-term cancer outcomes and short-term morbidity and mortality were comparable with those of the younger cohort. The International Society of Geriatric Oncology have comprehensive recommendations on staging, surgery and radiation/chemotherapy in the older patient with colorectal cancer.
Iron therapy should be initiated to correct anaemia and to replenish iron stores. This can be done using oral iron preparations, which are an effective and a cheap solution. Parenteral iron therapy should be used in severe iron deficiency or in non-compliance with oral therapy. Two preparations are commonly used – iron sucrose and ferric carboxymaltose. Iron sucrose is given in divided doses over a number of days whereas ferric carboxymaltose can sometimes replenish stores with one dose or can be given weekly as indicated. Anaphylaxis is a common adverse reaction and a test dose of both should be given. It is recommended that iron therapy should not be used in those with mild iron deficiency with no anaemia. High iron stores have been shown to be associated with an increased cancer risk. It may also be implicated in Alzheimer’s disease with redox-active iron accumulation being shown in neurofibrillary plaques and tangles.
Red cell transfusions should usually be avoided in the context of iron deficiency anaemia. Iron deficiency anaemia is usually a chronic picture, which does not require immediate treatment by transfusion. The British Society of Gastroenterology guidelines on iron deficiency do not mention RCC transfusion in their guidelines on management of iron deficiency. An exception to this would be a patient with symptomatic cardiovascular disease or perhaps preoperatively. The British Society for Haematology guidelines would only suggest red cell transfusion in chronic anaemia only if the anaemia was life threatening.
Iron deficiency in the older, frailer patient
Frailty is a difficult concept to diagnose, with many different tools available. Signs and symptoms of frailty include loss of muscle strength, increasing fatigue, loss of appetite and loss of physical independence. The British Geriatrics Society define frailty as “a distinctive health state related to the ageing process in which multiple body systems gradually lose their in-built reserves. Older people with frailty are at risk of unpredictable deterioration in their health resulting from minor stressor events”. This subgroup of patients tend to have frequent hospital admissions, recurrent falls and poor mobility, polypharmacy, complex chronic disease management, and poor functional status.
Depression, neglect and poor diet in the frailer older person can contribute to mild iron deficiency. Geriatric comprehensive assessment and multidisciplinary team assessment are important in these cases.
In these patients, symptom management should be the mainstay of treatment. Investigations should be curtailed to a minimum and only be done if thought to be beneficial and benefits outweigh potential risks.
The initial investigation for iron deficiency can be completed in the community. Referral for endoscopy for healthy older adults is the next step in investigating the cause of iron deficiency. The older, frail, multi-morbid patient should be referred to a geriatrician for comprehensive geriatric assessment and for advice of further investigation and management.
References available on request