Check Programme
The Hong Kong Practitioner VOLUME 25 / October 2003



Case one:

John Gregg is 71 years old and has a long history of rheumatoid arthritis. This is currently under reasonable control on a small dose of prednisone (6mg/day) and a nonsteroidal anti-inflammatory agent (naproxen). He presents with gradual onset of tiredness and ankle swelling over the past three months. On examination he looks pale and tired. His joints are not acutely inflamed, hot or swollen, but there is significant deformity associated with the long standing arthritis. His ankles are mildly oedematous.



Further history
The results of blood tests are as follows:
Hb - 94 g/L (reference range: 130 - 180g/L)
MCV - 82 fL (reference range: 80 - 98fL)
WCC - 12.8 x 109/L (reference range: 4.0-11.0 x 109/L)
white cell differential:
  - neutrophils 10.8 x 109/L (reference range: 2.0 - 7.5 x 109/L)
  - lymphocytes 1.4 x 109/L (reference range: 1.4 - 4.0 x 109/L)
  - monocytes 0.6 x 109/L (reference range: 0.2 - 0.8 x 109/L)
platelets - 535 x 109/L (reference range: 150 - 450 x 109/L)
ESR - 68mm/hour (reference range: 0 - 30mm/hour).
   
HK Pract 2003;25:511-514


Question 1: What is your interpretation of these results?
Answer 1
The patient has a normocytic anaemia. There is also a mild leucocytosis due to a neutrophilia, a mild thrombocytosis and an elevated ESR.



Question 2: What are the possible causes?
Answer 2

The cause of the anaemia in this situation may be complex and multifactorial. The anaemia of chronic disease is the most likely cause. This is an extremely common cause for anaemia, with only iron deficiency being more common. It is a poorly understood condition often found in chronic inflammatory disorders such as rheumatoid arthritis, malignancy or chronic infection. It is characterised by a low serum iron in the presence of adequate iron stores. The pathogenesis is complex, involving a mild shortening of red cell survival, an inappropriately low production of erythropoietin for the degree of anaemia, impaired marrow response to erythropoietin and abnormal iron metabolism.

However, patients with the anaemia of chronic disease may also have co-existent causes of anaemia and the laboratory abnormalities considered classic of other causes may not be present. Iron deficiency may be due to gastrointestinal blood loss related to gastric erosions or ulceration. Folate deficiency may be related to poor diet and difficulty with manipulating eating utensils due to the joint deformity. The presence of the anaemia of chronic disease or co-existent iron deficiency may mask the macrocytosis that is usually seen with vitamin B12 or folate deficiency. Haemolytic anaemia may also occur in autoimmune diseases and should be excluded.

Table 1: More common causes of vitamin B12 deficiency
Nutritional Vegans
  Breastfed infants of mothers with untreated B12 deficiency
   
Malabsorption Defective proteolysis of vitamin B12 from food
  Gastric achlorhydria
  Partial gastrectomy
  Proton pump inhibitors
  H2 antagonists
     
  Lack of intrinsic factor
  Pernicious anaemia
  Total gastrectomy
     
  Disorders of the terminal ileum
  Crohn's disease
  Resection
     
  Pancreatic disease
     
  Competition for vitamin B12
  Bacteria ('blind loop' syndrome)



Question 3: How would you investigate further?
Answer 3
It would be appropriate to order iron studies and serum vitamin B12 and red cell folate assays. As discussed in Case 3, in complex situations like this, iron studies may not give a clear indication of the presence of iron deficiency and a bone marrow assessment of iron stores will then be required. A direct anti-globulin (Coomb's) test will determine if there is any immunoglobulin coating the red cells. If positive, it raises the possibility of an auto-immune haemolytic anaemia. However, it is possible to have a positive anti-globulin test in the absence of haemolysis. Tests to exclude other diseases associated with anaemia are also indicated (serum creatinine, liver function tests, thyroid function tests).



Further history
In John's case the vitamin B12 and red cell folate levels were normal. Iron studies showed a low serum iron and low serum transferrin, consistent with the findings in patients with the anaemia of chronic disease. The serum ferritin was elevated at 380 , reflecting the role of ferritin as an acute phase reactant. The Coomb's test was negative. Renal and liver function tests were normal. The final diagnosis was therefore the anaemia of chronic disease.


Question 4: What is the treatment of the anaemia of chronic disease?
Answer 4
The primary treatment is that of the underlying condition. The anaemia is rarely severe enough to be of clinical importance, although it is wise to monitor the haemoglobin level. Some patients may have symptoms that justify transfusion (e.g. developing angina at a particular haemoglobin level). Erythropoietin is effective in many cases but is expensive and not funded for this indication in Australia.


Royal Australian College of General Practitioners