Suzanne was a 54-year-old librarian who I had not seen before in surgery. She reported feeling nauseous and tired and, curiously, she thought her skin had taken on a yellow colour.
When pressed for further symptoms she admitted to shortness of breath on exercise and possibly weight loss but denied abdominal pain, dysphagia, rectal bleeding, change in bowel habit or change in colour of stool or urine.
Suzanne thought her symptoms may have first appeared around six months previously but had become progressively more intrusive since then.
Although Suzanne's sclera looked clear her skin did appear to have a yellow tinge to it. She was not tachypnoeic at rest but was tachycardic, with a regular pulse of 108 beats per minute.
Her chest was clear, heart sounds were normal and there was no calf swelling or tenderness. Abdominal examination revealed no tenderness, masses or organomegaly.
Iron deficiency anaemia was listed in her medical history 20 years previously, but other than a few minor gynaecological procedures the remainder of the history was unremarkable.
Suzanne was a lifetime non-smoker, consumed alcohol in only small quantities, ate a well-balanced diet and did not take any regular medication.
My first thoughts were to exclude anaemia and thyroid disorder and to check for renal or hepatic dysfunction. Blood tests were arranged accordingly.
Suzanne was called back in urgently on receipt of the blood tests, which showed a severe macrocytic anaemia with a haemoglobin of 5.2g/dL and a mean cell volume (MCV) of 112fL.
Her white cell count was adequate, although platelets were on the low side at 131 x 109/L. Her bilirubin level was elevated to 59 micromol/L with other LFTs normal. U&Es, TFTs and fasting glucose levels were normal with an ESR of 19mm/hr.
Possible underlying diagnoses of a macrocytic anaemia are listed in the box. Given the blood test results, the most likely causes in Suzanne's case were B12 or folate deficiency, a haemolytic anaemia or myelodysplasia.
At this point I was considering hospital admission, but the advice following a phone call to the haematologist was that hospital admission and blood transfusion were probably unnecessary and that B12 and folate levels would be assessed urgently. If the latter were normal then analysis of bone marrow would be indicated.
The absence of a significant reticulocytosis argued against haemolytic anaemia as being a primary cause of the anaemia.
B12 levels were reported as being very low with repeat analysis to be performed on a separate analyser. Ferritin and folate levels were within normal range.
The diagnosis was pernicious anaemia. Suzanne started a series of six IM injections of 1mg hydroxocobalamin over of two weeks and also given supplementary folic acid and ferrous sulphate to support erythropoiesis.
Within a week of commencing treatment Suzanne was feeling much better, with resolution of nausea, increased energy and reduced shortness of breath. Repeat blood testing gave a haemoglobin level of 7.5g/dL, an MCV of 107fL and normal platelet and bilirubin levels.
After a month Suzanne's haemoglobin had climbed to 11.4g/dL and MCV had normalised. She was advised to have lifelong three-monthly hydroxocobalamin injections.
Vitamin B12 is an essential factor in the synthesis of thymidine and DNA, so deficiency will lead to impaired red blood cell production. Intrinsic factor produced in the stomach binds to B12 and this complex is subsequently absorbed in the terminal ileum.
Deficiency of B12 usually arises either from poor intake (notably a vegan diet, as B12 is not found in plants) or from malabsorption, either because of lack of intrinsic factor from the stomach (pernicious anaemia of post-gastrectomy), or because of dysfunction of the small intestine (Crohn's disease or ileal resection).
If malabsorption is the problem then B12 must be given intramuscularly.
Pernicious anaemia is an autoimmune atrophic gastritis in which parietal cell and intrinsic antibodies are produced. It is associated with other autoimmune conditions and has a female preponderance.
A mild jaundice can be seen in pernicious anaemia because relatively abnormal red cells produced by the compromised marrow are haemolysed, liberating bilirubin. There may be an accompanying leukopaenia and thrombocytopaenia, which are rapidly corrected on initiation of B12 supplements.
B12 deficiency can lead to a peripheral neuropathy, typically reported as a symmetrical paraesthesia of hands and feet, ataxia, weakness, glossitis, angular stomatitis and, in the elderly, a reversible dementia.
- Dr Morris is a GP in Shrewsbury, Shropshire
|Differential diagnoses of macrocytic anaemia|